Journal of Genetic Counseling, Vol. 7, No. 6, 1998

Abstracts from the Seventeenth Annual Education Conference of the National Society of Genetic Counselors (Denver, Colorado, October 1998) Denise Tilley1,3 and Kelly Ormond2 Abstracts have been arranged by the Abstract Committee into the following categories: I. Award Papers II. Issues in Cancer Genetics III. Clinical Genetics and Screening Issues IV Process and Psychosocial Issues V The Expanding Role of the Genetic Counselor PAPERS AWARDED PRIZES FOR BEST RESEARCH BY AN NSGC MEMBER AND BEST RESEARCH PERFORMED WHILE A GENETIC COUNSELING STUDENT Psychosocial Assessment in Prenatal Genetic Counseling: An Assessment of Current Methods and Interest and the Development of the Psychosocial Assessment of Prenatal Patients (PAPP) Form J. Yelland, M. Walker, J. Zins, and N. Warren University of Cincinnati, Cincinnati, Ohio 45229 The importance of psychosocial assessment in the medical care of patients is well documented. However, there has been no research conducted on the role of preliminary psychosocial assessment in the prenatal genetic counseling setting. The objectives of this study were to review the psychosocial assessment methods currently utilized by prenatal genetic counselors, assess their interest in using a psychosocial assessment tool, and pilot a newly devised form. First, an extensive review of published literature was conducted, focusing on methods 1Women's

Institute, Carolinas Medical Center, Charlotte, North Carolina. University, Chicago, Illinois. 3Correspondence should be directed to Denise Tilley, Carolinas Medical Center, Women's Institute, P.O. Box 32861, Charlotte, North Carolina 28232. 2Northwestern

445 1059-7700/98/1200-0445$15.00/1 C 1998 National Society of Genetic Counselors, Inc.

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and tools designed for the psychosocial assessment of patients with a variety of medical conditions. Psychosocial parameters measured by each tool were categorized and the parameters determined appropriate for use in the prenatal genetic counseling setting were incorporated into the Psychosocial Assessment for Prenatal Patients (PAPP) form. The PAPP is a one-page collection of 19 statements addressing seven categories: Family and Social Support (FSS), Anxiety Level (AL), Risk Perception (RP), Sense of Well-Being (SWB), Physical Environment (PE), Family Concept (FC) and Coping Skills (CS). Response choices were based on a 5-point Likert scale to indicate the extent to which the patient agreed with the statement. Second, two subject sources were recruited for this study. The first subject group consisted of all members of the 1998 National Society of Genetic Counselors (NSGC) Prenatal Special Interest Group (SIG) currently residing in the United States. The second subject group was comprised of genetic counselors and patients from three prenatal centers. Third, a brief questionnaire was developed for determining the current methods of psychosocial assessment utilized in prenatal counseling prior to the genetic counseling session. Center demographics, information about the counseling session and prenatal intake procedures were also addressed. Counselors were asked to return a copy of their centers' pregnancy and medical history forms along with the completed questionnaire. Fifty-five questionnaires were returned, yielding a response rate of 46.2%. Respondents represented 53 centers in 30 states. Intake forms from 33 centers (32.0%) were provided by respondents. Review of the collected intake forms confirmed that no routine written materials are designed to assist in the documentation of thoughts, feelings, concerns, and beliefs of pregnant women. Finally, the PAPP form and a three-page evaluation form were sent to the original counselor subject group for counselor assessment of the PAPE Forty-one counselors returned the evaluation form, giving a response rate of 34%. A majority of counselors (71%) reported that they were interested in having a standard psychosocial assessment form available for use. The categories of AL, RP, CS, and FSS were rated "very important" by the majority of counselors (81.6%, 68.4%, 67.6%, and 60.5%, respectively). The majority of counselors also reported that they felt the PAPP form would help them better understand their patients' psychosocial status in the categories of FSS (55%), SWB (70%), and AL (67.5%). Many counselors also indicated potential barriers to using the PAPP form at their respective center of employment. In order to determine how the PAPP might be utilized in a true setting, the PAPP form was administered to approximately 60 prenatal patients seen for genetic counseling at two prenatal centers in Ohio and one in Alabama. While results regarding the administration, evaluation, and efficacy of the PAPP are pending, the completed portion of the study indicated high interest in such a form. The final results of this study will help describe the role of and need for pre-counseling psychosocial assessment in the delivery of effective genetic counseling. Response to Learning Carrier Status: Effect on Self-Concept A. McConkie-Rosell, G. Spiridigliozzi, D. Dawson, J. Sullivan, K. Rounds, and A. Lachiewicz Duke University Medical Center, Durham, North Carolina 27710 Central to many discussions of carrier testing is the concern about harm to self-concept. The majority of studies designed to evaluate the impact of carrier testing on self-concept have used recessively inherited conditions, such as cystic fibrosis, as disease models. At this point, however, little information is known regarding the impact of and feelings related to being tested to determine carrier status for X-linked disorders. The purpose of the fragile X "at-risk" study is to explore the attitudes, opinions, and feelings regarding knowledge of carrier status of women at risk for inheriting the fragile X mutation. For the purpose of this study, selfconcept was defined as an individual's sense of self and self-perception as it relates to identity, feelings, thoughts, behavior, appearance, and personal characteristics. In this longitudinal study, the sample consisted of women over the age of 18 years who are members of fragile X families and were at risk for having inherited the fragile X mutation through pedigree analysis. The majority of the 47 women enrolled in the study had a 50% a priori risk. Pretest measures were obtained prior to learning carrier status and the posttest measures occurred

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6 months (±6 weeks) after learning the results of the DNA carrier testing. Operationally, self-concept was measured by the Tennessee Self-Concept Scale (TSCS). In addition to the TSCS, feelings related to "degree of upset" experienced secondary to learning "at-risk" status (pretest) and "degree of upset" at learning carrier status (posttest) was measured using a fragile X visual analog scale (fra(X) VAS), scored from 0 to 10, and a structured interview. Responses to the structured interview offer descriptive statements of how participants view both their initial status of being "at risk" and follow-up information regarding their feelings about learning the result of their carrier test. Preliminary analysis found no significant changes on the total score or subscales of the TSCS in any of the women tested. However, changes in feelings regarding self and degree of upset were identified on the fra(X) VAS and the structured interview. Analysis of the pretest fra(X) VAS indicates that overall women felt that learning "at-risk" status was upsetting (mean = 4.55, SD = 1.57) and fragile X was a very serious problem (mean = 2.63, SD = 2.84). Analysis of the posttest fra(X) VAS completed at the 6-month counseling session indicated that noncarriers report improvement in feelings regarding self (p = .039) and viewed fra(X) syndrome as significantly more serious than carriers (p = .043). In addition, carriers indicated a greater level of upset regarding their carrier status both when initially informed of the test result (p < .000) and at follow-up (p < .000). Responses from the structured interview indicate that the degree of upset and changes in feelings regarding self are not related to self-concept, but are instead the result of concerns regarding reproduction for self, children, and grandchildren. This additional information, coupled with the stability of self-concept throughout the genetic testing process, highlight areas related to testing that warrant further investigation and may ultimately result in modifications to the genetic counseling provided during discussions of carrier testing. Prophylactic Oophorectomy: Patient Characteristics and Postdecision Adjustment S. Babb, E. Swisher, A. Whelan, C. Skinner, D. Mutch, and J. Rader Washington University School of Medicine, St. Louis, Missouri 63110 Epithelial ovarian cancer is the most common cause of death from gynecological malignancies in the United States with a 5-year survival of only 31%. Women with family histories of cancer may be at markedly increased risk for ovarian cancer, but have few options to reduce their risk of ovarian cancer. Surveillance for ovarian cancer through pelvic examination, transvaginal ultrasound, and serum CA-125 levels are offered, but have not been proved effective. Prophylactic oophorectomy is thought to significantly reduce but not eliminate the risk for developing ovarian cancer. In addition to acute surgical morbidity and mortality, prophylactic oophorectomy in premenopausal women causes the abrupt onset of menopause and increased risk of osteoporosis and heart disease without estrogen replacement. The procedure has been sought by women at high risk for ovarian cancer and endorsed by the NIH, gynecologic oncologists, and geneticists, as a potential alternative to screening for high-risk women provided they are appropriately informed of its limitations. The decision is complex and difficult and has the potential for serious physical and psychological impact. Unfortunately, information on which to base counseling is lacking. The objectives of this study are to: (1) describe the demographic characteristics and medical and family histories of women who have undergone prophylactic oophorectomies and compare these with the demographic characteristics and medical and family histories of women who have opted against prophylactic oophorectomy, (2) describe and compare perceptions about the information gathering and decision-making process, (3) explore factors seen as having influenced the decision to undergo or to decline prophylactic oophorectomy, and (4) assess postdecision psychological functioning and quality of life. This study employs an in-depth telephone interview which includes a series of open-ended, exploratory questions about breast and ovarian cancer risk perceptions and factors which influenced the decision-making process and postdecision physical and psychological well-being. We are in the process of interviewing 30 women who have undergone prophylactic oophorectomy through physicians affiliated with Washington University Medical Center in the last 6 years. We are also interviewing a comparison group of 30 women who

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have been offered the option of prophylactic oophorectomy because of a significant family history of cancer but have opted against surgery. At the time of abstract submission, 17 interviews have been completed. Data analysis is ongoing. The results of this study will improve the ability of health professionals to counsel women who are considering prophylactic oophorectomy. Comprehensive Risk Assessment Program for Menopausal Women: Impact of Genetic Counseling T. Bardakjian, L. Steinberg, E. Mack, T. Sellers, L. Jablon, S. Dickinson, and A. Schneider

Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141 Women approaching menopause are faced with many decisions which potentially affect their health for the rest of their lives. A primary issue is whether or not to begin hormone replacement therapy (HRT) at the onset of menopause. Although there is convincing evidence that HRT reduces a woman's risk of cardiovascular disease and osteoporosis, some reports have shown a possible increased risk of breast cancer in women undergoing long-term HRT It is this potential increased risk of breast cancer which often deters women from HRT, especially those with a family history of breast cancer, although the benefits for individual women may far outweigh the potential risks. Tb address this complex issue, an innovative risk assessment program for menopausal women with a family history of breast cancer, coordinated by a genetic counselor, was piloted at the Albert Einstein Medical Center in Philadelphia with funding provided by the Albert Einstein Society. Each participant was seen for two separate sessions. During the first session each women met with a genetic counselor for pedigree construction, an educational session explaining the genetics of cancer, breast cancer risk factors and the multifactorial nature of conditions such as heart disease and osteoporosis. A nurse then discussed menopausal symptoms and treatment and provided instruction on breast selfexam. A bone density study to evaluate for osteoporosis was performed on each participant. An EKG and lipid profile were also reviewed to identify risk factors for heart disease. The genetic counselor reviewed and analyzed the pedigrees to determine the woman's estimated risk to develop breast cancer. Once all results were compiled, the genetic counselor presented the woman's profile to a multidisciplinary panel of medical experts. A discussion regarding the risks vs. benefits of HRT use for each woman ensued and recommendations were made. The second session included a meeting with the genetic counselor and breast surgeon to review the assessment results and panel recommendations. The breast surgeon also performed a clinical breast examination and reviewed the woman's mammography films. The woman then met with the dietician to review her lifestyle and diet questionnaire. Prior to the start of the first session each participant was given a pretest which included questions about her perception of her risk to develop breast cancer, osteoporosis, and heart disease (lower than average, average, higher than average, or extremely high). Each participant was also given a posttest at the conclusion of the program to assess any change in her risk perception. We report data from the pre- and posttests of the first 45 women who completed the program. We analyzed the responses for any adjustments in how each woman perceived her risk of developing breast cancer, osteoporosis, and heart disease. Of the 45 women, 21 (47%) overestimated their risk of developing breast cancer on the pretest. After completing the program and receiving their individualized risk assessment, 14 of the 21 women (67%) appropriately decreased what they believed to be their risk for developing breast cancer. Seven of the 21 women (33%) continued to overestimate their risk on the posttest. Seven of the 45 women (15%) underestimated their risk to develop breast cancer on the pretest. Of these seven women, five (71%) correctly increased their perception of their risk on the posttest, while the other two (29%) continued to underestimate their risk. The remainder of the women, 17 of 45 (38%) had estimated their risk to be similar to our risk assessment. Fifteen of the 17 women (88%) maintained this accurate perception on the posttest. Data regarding the participants' risks of developing osteoporosis and heart disease showed similar trends. We will elaborate on this data which illustrates how our program adjusts a woman's perception of her risk to develop certain conditions. This adjustment can then assist her in making informed decisions regarding her health care.

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Oncologists' Attitudes on Genetic Testing for Breast Cancer Suggest an Opportunity for New Collaborative Efforts J. Bars, J. Hull, D. Dunne, and W. Burke

University of Washington, Seattle, Washington Since cancer genetic testing has become available, medical professionals can now provide genetic information to their patients that is potentially useful in clinical decision-making. In order to determine how oncologists use genetic testing for breast/ovarian cancer and the extent to which they are utilizing clinical genetics services, a survey was sent in June, 1997 to all oncologists treating adult patients in the Pacific Northwest (Washington, Oregon, Idaho, and Alaska) who were members of their state medical associations. Out of 264 surveys sent, 135 (51%) responses were received. The oncology specialties of respondents were: medical (42%), radiation (27%), hematological (22%), gynecological (5%), and other (3%). Survey respondents had a mean age of 47 (±8) years, and 81% were male. Virtually all (98%) respondents reported seeing patients for breast or ovarian cancer in their practice. Most (79%) had discussed genetic testing for breast/ovarian cancer with patients but few (22%) had offered patients testing. Only 19% of oncologists felt their practice had the necessary services and staff to offer genetic testing. Oncologists who offered testing were more likely to rate themselves as knowledgeable in cancer genetics, to have had contact with a genetic counselor, and to have received marketing materials about genetic testing. Among all respondents, a total of 25 patients had been tested by 16 oncologists (12%). Although 76% of oncologists wanted their patients who consider testing to consult with a genetic counselor, only 30% of oncologists had contact with a genetic counselor, and only 16% had referred for testing to genetics professionals or other specialists. When asked to choose which health professionals they consider appropriate to provide pretest information to patients, respondents selected: genetic counselors (84%), oncologists (77%), genetics physicians (72%), nurses with training in genetic testing (56%), and primary care physicians (21%). On average, respondents indicated that 52 (±8) minutes should be provided for a pretest information session. Sixty percent of respondents felt patients should sign a formal consent form for testing. The majority rated their knowledge above-average in cancer genetics and showed strong interest in continuing education. Overall, although most oncologists who responded to the survey supported pretest counseling and the use of genetic services, few had made contacts or actual referrals to genetic counselors. Initiatives to increase communication and collaboration between the two disciplines represent an important priority for genetic counselors. Genetic Counseling for Familial Colorectal Cancer and Molecular Testing for FAP or HNPCC in Israeli Families A. Ben-Yehuda, A. Orr-Urtreger, R. Shomrat, T. Naimann, I. David, M. Kedmi, H. Turgeman, Z. Samuel, P. Rozen, and C. Legum

Sourasky Medical Center, Tel-Aviv, Israel 64239 Colorectal Cancer (CRC) is one of the commonest forms of cancer in the Western world and in Israel. The majority of CRC patients are sporadic, but about 10% are familial. The Sourasky Medical Center in lei-Aviv is conducting an oncogenetic consulting service for familial CRC. The service is a joint project of the departments of gastroenterology and genetics. Members of families with CRC underwent a gastroenterologic evaluation first and were then referred to the department of genetics for preliminary genetic counseling. This included the construction of a pedigree, followed by a general explanation and discussion about the molecular testing for either Familial Adenomatous Polyposis (FAP) or Hereditary Non Polyposis Colorectal Cancer (HNPCC). Any patient or family member deciding to proceed with molecular testing signed informed consent. After obtaining results, the patient and family were invited for a second genetic counseling session. This included an explanation and discussion

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about test results and their implications, and recommendations for further clinical follow-up. The family was then referred back to the department of gastroenterology. During any stage of this process, an oncologic psychologist could be consulted, if needed. Until April 1998, we saw 120 unrelated families who were referred for genetic counseling and molecular testing because of CRC. Among these families, two were diagnosed with Peutz-Jegher syndrome, five with Juvenile Polyposis, 35 with FAP, and 78 with HNPCC or unspecified familial CRC. Among the 35 FAP families a mutation in the Adenomatous Polyposis Coli (APC) gene was identified in 22 probands. In five families, no mutation was found and genetic counseling was given according to linkage analysis. Six families are still undergoing molecular testing of the APC gene and in two families, no DNA was available for testing. Among the 78 HNPCC and unspecified familial CRC, there were 27 families who met all three, or at least two of the Amsterdam Criteria (AC). In five of them, a mutation in one of the DNA mismatch repair genes, hMSH2 or hMLHl, was found. Twenty six families fulfilled only one AC. In one of these families, a mutation in hMSH2 was found. Five families do not meet any AC. DNA of 20 families was not available for testing. In families in whom a mutation was found in the proband, it was possible to identify the mutation in other family members before the appearance of cancer and to give meaningful genetic counseling to each family member undergoing molecular analysis. Genetic Counseling Issues in Hereditary Paraganglioma L. Chiu, L. J. Rlttmeyer, J. Peters, and W. S. Rubinstein

University of Pittsburgh, Department of Human Genetics, Pittsburgh, Pennsylvania While hereditary breast, ovarian, and colon cancer syndromes account for the majority of patients seen in the cancer genetics setting, other inherited cancer predisposition syndromes exist and should be recognized by the cancer genetics provider. The purpose of this abstract is to summarize the clinical and genetic features of hereditary paraganglioma and to discuss the special counseling issues that can arise. Paragangliomas are rare, occurring in 1:30,001:100,000 individuals. They are slow growing tumors of neuroectodermal origin. Paraganglioma tumors are generally named for the neural structure in which they arise (carotid body tumor, glomus jugulare, glomus tympanicum, glomus vagale, and chemodectoma). While the majority of cases appear to be sporadic, at least 10% of paraganglioma cases are inherited. Pheochromocytoma can also be seen as part of the hereditary paraganglioma syndrome. Paragangliomas are usually benign; however, progressive growth can lead to problems such as localized swelling, cranial nerve injury, facial paralysis, deafness and hoarseness. After years of growth, approximately 4-10% of tumors will become malignant and go on to form metastases. Early diagnosis through MRI is critical for the option of surgical removal to reduce the extensive morbidity associated with these growths. The onset of symptoms related to tumor growth usually leads to detection in the mid-30s. In order to detect tumor growth before symptoms arise, screening for tumors of the head and neck with MRI and for pheochromocytoma with urinary catecholamine levels is recommended every 2 years starting at age 16-18 for individuals at risk. The predisposition to develop paragangliomas is an autosomal dominant condition subject to genomic imprinting with 95% penetrance by age 50. Children of male carriers are susceptible to paragangliomas, while children of female carriers are not considered to be at risk. Males who inherit the altered gene from a female, while unaffected, can pass the altered gene on to their children who would then be at risk. A loci at 11q22.3-q23 has been implicated in hereditary paraganglioma. The identification of the paraganglioma gene will allow for predictive testing for individuals at risk, eliminating the need for costly screening in individuals without the familial mutation. For now, genetic counseling to provide extensive analysis of the family history and consideration of the imprinting mechanism is used to identify individuals at high risk of developing paragangliomas. Haplotype analysis is available in the research setting and can identify those individuals who have inherited the at-risk allele. In this abstract, we present two illustrative cases seen in the Cancer Genetics Program of the University of Pittsburgh Cancer Institute and Magee-Womens Hospital. Case 1 is a typical hereditary para-

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ganglioma family that demonstrates autosomal dominant inheritance with imprinting. To further illustrate the complexity of counseling for hereditary paraganglioma, a family that does not appear to follow the imprinting phenomenon is also presented. In the event that the imprinting rule is broken in this family, individuals previously identified as low risk would now be candidates for screening. The actual proportion of paragangliomas that are hereditary may be higher than the 10% currently estimated. The appearance of skipped generations due to imprinting and the slow growing nature of these tumors may distort the true incidence of hereditary paraganglioma. It is anticipated that through greater understanding of the clinical and genetic aspects of hereditary paraganglioma, more individuals with this unique condition will be identified and appropriately counseled with regard to their risk. Genetic Counseling for BRCA1 Mutation Testing in a Large Family Setting S. Clark, K. Regan, L. Bluman, B. Rimer, J. Schildkraut, and D. Iglehart Duke University Medical Center, Box 2949, Durham, North Carolina 27710 We are reporting on a large kindred in which a BRCA1 mutation was identified in the proband. Counseling and testing were done through a university-based study looking at how women make informed decisions about BRCA1/2 testing. Subsequently, an additional 27 women in the family, through four generations, were invited to participate in the same research project and offered the option of free testing. Participants within this family were offered the option of individual genetic counseling at Duke University Medical Center or participation in a group counseling session with other family members in their local area. Twenty of the women indicated a preference for the group counseling setting, some of whom were involved in the organization of the event. The counseling session, scheduled for May 30, 1998, will include a 45-minute group presentation about genetics and the risks, benefits, and limitations of genetic testing. Each woman will then meet individually with a genetic counselor for a period of about 20 minutes to discuss individual concerns, questions, and her personal risk estimate. Participants will be consented individually and will be offered confidential phlebotomy in a separate room. We will report on this general process, as well as results from an evaluation survey. A combination of multiple choice, scaled, and open-ended questions will be used to capture participants' concerns, perceptions, and overall satisfaction with the group event. The evaluation will include questions regarding confidentiality issues, family dynamics, information sharing, and perceived effectiveness of the group presentation. Some women within the family will meet for the first time during this event. We will describe potential confidentiality conflicts associated with displaying a composite pedigree in the group presentation. Individual family unit pedigrees will be used during the shorter, personal interactions with the participants. We will assess participants' degree of comfort with each part of the group counseling process, satisfaction with individual testing decisions, factors influencing their testing decisions, and concerns arising from the group setting. Potential Benefits of DNA Banking in Families with Unclassified Variants in BRCA1/2: Case Report S. Clark, J. Schildkraut, D. Iglehart, A. Miron, J. Futreal, and A. Futreal Duke University Medical Center, Box 2949, Durham, North Carolina 27710 Unclassified variants (UVs) within the BRCA1/2 genes have been commonly reported with the increase in genetic counseling and testing for these disease genes. This poses a difficult counseling situation as these are uninformative results and cannot be classified as either disease causing mutations or as polymorphisms without additional information, such as the population frequency of the variant or how it segregates in relation to the cancer in the family. Coupled with a breast cancer family DNA banking effort, we have been able to use segregation/haplotype analysis in a research setting to show in one family that an unclassified variant

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in BRCA2 found in an affected proband is not a disease-causing allele. The proband in this family was diagnosed with breast cancer at age 36 and has two sisters and a paternal aunt with early-onset breast cancer. The proband was given the UV result and counseled that the significance of this finding was unknown at present. As a standard part of the research protocol, she was invited to include her family in a DNA banking project at Duke University. Multiple affected and unaffected members of the family were willing to donate their blood for this project. By genotyping several affected and unaffected family members for the observed variant in BRCA2 as well as haplotying for three markers on chromosome 13 flanking the BRCA2 gene, we were able to show that this UV did not segregate with the cancer in the family. The family, as a group, was recounseled that the UV found in the proband was not tracking with the cancer in the family and therefore, was very unlikely to be a disease causing mutation. The lack of sharing of both the UV and a common chromosome 13 haplotype in affected family members provided evidence that this specific BRCA2 allele is a presumably benign polymorphism. The availability of DNA samples on multiple family members was key to determining segregation of the UV in this family. In some families, as in this one, testing specific additional family members may provide useful, interpretable information. Improving Participation by African Americans in Cancer Genetics Studies S. Cummings, A. Mathews, S. Turner-Thompson, V. Wohl, and O. I. Olopade University of Chicago, Chicago, Illinois 60637 The identification of major cancer susceptibility genes that can confer increased risk for cancer when inherited in a mutated form offers high risk individuals the opportunity to learn if they are genetically predisposed to cancer. Although African Americans bear a disproportionate burden from cancer mortality, participation of African Americans (AA) in cancer genetics study has been exceedingly low. To explore ways of improving AA participation, we commissioned a qualitative research project to facilitate development of understandable and culturally sensitive informational materials for AAs seen in our clinic. The objectives of the study were: (1) to determine the informational needs of AAs regarding genetic testing for breast, colon, ovarian, and prostate cancer, and (2) to identify factors contributing to the lower participation of AAs in genetic testing for cancer. A trained focus group moderator led three groups (n = 21) through a series of open-ended questions. The groups consisted of AA men (n = 8) and women (n = 8) with a family history of breast, colon, ovarian, or prostate cancer as well as five AA women who had previously participated in one of our cancer genetic testing protocols. The mean age was 42 years (range 25-57). Participants were typically employed (63%), female (62%), well educated (67% had at least some college), and had an average annual income of $15,000 or greater. Overall cancer knowledge of participants was variable but very poor for knowledge of BRCA1. Many concerns expressed by participants were similar to those previously reported (e.g., confidentiality of test results and insurance discrimination). However, embedded within the more universal concerns were attitudes and experiences not typically reported. These included lack of awareness of the role of genetic counseling and testing in cancer risk assessment, poor cancer communication among family members because it is a "taboo" topic, perceptions about cancer survivability, the emotional reactions to the long multistep process of genetic testing and fear and/or distrust of "experimentation" by the medical community. At the same time, participants acknowledged the universality of the human experience with cancer, and the desire to be treated "like everyone else." Some recommendations for improving participation include: (1) provide a forum where AA with family histories of cancer can discuss issues related to cancer; (2) use a local spokesperson or community leader who is AA, a cancer survivor, or has participated in genetic testing to speak at community centers; (3) develop a media campaign using a celebrity spokesperson who is AA, has had cancer or has a family history of cancer; (4) provide a toll-free or local phone number for people to call with any questions about genetic testing; and (5) use community centers and high traffic areas such as churches, public transportation, schools, park district centers, and libraries to distribute written information and post the toll-free or

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local phone number. Thus, in addition to increasing basic awareness of the role of genetic counseling in cancer management, the genetic counseling and testing process should be streamlined to fit the informational preferences of African Americans. Supported by Grants NCI #14599-24 to the University of Chicago Cancer Research Center, and the Washington Square Foundation. Information at Your Fingertips: National Cancer Institute Resources and Materials for Genetic Counselors E. Dean-Clower, K. Crosson, and I. Liu National Cancer Institute, Bethesda, Maryland 20892-2580 Genetic counselors are challenged to translate complex medical and scientific information about genetics and risk and to assist individuals and families in making medical decisions and health related lifestyle choices. In the rapidly evolving field of cancer genetics, there is a need for accurate and appropriate education tools; training for genetic counselors specific to cancer is also necessary. This session will address the variety of education and informational resources available at the Federal level which will assist cancer genetic counselors to meet the needs of their clients. The presenter will discuss the results of a needs assessment survey conducted by the National Cancer Institute in 1996. Survey results identified the need for new easy-to-understand education resources and training. In addition to describing print and web-based materials and how to access these resources, the presenter will elaborate on NCI's current and future cancer genetics education efforts. Psychosoclal Issues and Breast Cancer In South African Ashkenazi Women C. de Vos, B. Rapoport, and J. Kromberg Department of Human Genetics, University of the Witwatersrand, South African Institute for Medical Research, Johannesburg, 2000 South Africa The strongest determinants of a woman's risk of developing breast cancer are age and a positive family history. Ashkenazi Jewish women seem to be at increased risk for breast cancer and genetic counselors are beginning to understand the genes involved in this susceptibility, and the social and emotional impact on patients and their families. The aim of this study was to explore some of the psychosocial issues associated with breast cancer in Ashkenazi Jewish women in South Africa, and to investigate their knowledge of and feelings about breast cancer, its treatment, screening strategies, and genetic testing. The subjects (20) were all of Ashkenazi Jewish descent and over the age of 18 years. Ten subjects (experimental group, mean age 52.1 years) had been previously diagnosed with breast cancer and their names obtained form a Medical Oncology Center. Of these women, two had had bilateral mastectomies, four unilateral mastectomies, and four had had lumpectomies with radiation therapy. A further ten subjects (control group, mean age 56.7 years) were randomly selected from the study population and had not been diagnosed with breast cancer. Each subject was interviewed using a schedule of questions which was tested in a pilot study and differed slightly for the controls. Prior to their diagnosis (mean: 6 years previously, range 2-10 years), most women (70%) interviewed had never thought about their risks of developing breast cancer. However, most of the controls (90%) had considered their risk and had had screening for breast cancer. The emotions following a diagnosis of breast cancer included shock (three subjects), fear (three), anger (two), sadness (two) and a general feeling that the diagnosis was life altering. There was no obvious correlation between type of treatment and poor self-image. One of the women had had reconstructive surgery and three women regretted not having this surgery (two had had lumpectomies and one a unilateral mastectomy). Half of the women reported changes in their relationships with their partners relating to negative self-image, sexual relations, and communication breakdown. Most (70%) of the diagnosed women felt they had

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received the best possible treatment and (60%) were satisfied with the care given by their doctors. However, most subjects reported that their doctors did not discuss the emotional aspects of the diagnosis with them. Those doctors that did so (three), left their patients feeling calmer and in control. The majority of subjects in both groups (90%) felt that women diagnosed with breast cancer would benefit from seeing a psychologist, social worker, or a genetic counselor, and that this service should be made freely available to all such women and their families. Seven of the diagnosed women reported that their greatest fear was that their children would develop the condition. Eight of the experimental women and three of the controls reported that they would want genetic testing. The reasons for wanting testing were to learn if their children were at risk and to undertake more frequent screening and better care. The preliminary results of this ongoing study suggest that more education is required in this at-risk population. There appears to be insufficient emphasis on the risk in this population group and the advantages of screening for breast cancer and these issues need to be addressed. A diagnosis of breast cancer is accompanied by an array of emotions, and the psychological well-being of the patient is often neglected. Informed psychologists, social workers, and genetic counselors have an important part to play and referral to these experts should be increased. Utility of a "Patient-initiated" Risk Assessment Form in Designing a Cancer Genetics Information Service K. R. Eanet and M. M. Cohen Harvey Institute for Human Genetics, Greater Baltimore Medical Center, Baltimore, Maryland 21204 In an effort to tailor a cancer genetics information service for the patient population of the Greater Baltimore Medical Center (GBMC), a family cancer risk assessment questionnaire was designed soliciting information about the patient's own cancer, age at diagnosis, number and ages of other affected family members, and possible interest in genetic counseling and risk assessment. Approximately 800 questionnaires were circulated on the GBMC campus, to oncology specialists (surgical, medical and radiation oncologists) and general surgeons, as well as to general practitioners (family medicine, obstetricians, and gynecologists). The forms were located in physician waiting rooms, and were completed by the patients at their discretion (rather than by the physician or at his/her request), since it was felt that this would provide a more accurate picture of their perceptions of genetic cancers and their desire for genetic counseling. Questionnaires were not made a part of the medical record. After 6 months, we received 106 responses, mainly from women with breast cancer whose average age at diagnosis was 50.7 years and who had 2.9 additional relatives with cancer(s). The second most prevalent conditions were the hematological cancers, with an average age of diagnosis of 53.8 and an average of 1.9 affected family members. Other "genetic" cancers were found less frequently, including ovarian (4/106), colon (5/106), and prostate (3/106). Interest in genetic counseling varied, with about half of participants (47/106) indicating no desire for genetic counseling even though a number of them had ages of diagnoses and family histories suggestive of inherited cancer. Of 31 individuals who indicated that they were "maybe" interested in counseling, the majority (20/31) did not return two phone calls. Of the remainder, five were not interested when informed of the out-of-pocket cost; four did not have an understanding of what genetic counseling was; and two were interested only in specific personal questions. Of the 13 respondents who indicated an interest in counseling, five made appointments and were counseled. Four did not follow through because of the cost; and four did not return two phone calls. These five counselees represent a yield of approximately 20% of the positive responses: patients who might not have been referred for counseling. It is also important that of the 44 prospective patients who indicated that they were definitely or "maybe" interested in genetic counseling, nine (20%) lost interest when informed of the out-of-pocket expense, suggesting that the cost constitutes a significant barrier to providing counseling services. Based on the information gained, we have widened the scope of our cancer risk assessment and counseling services to include those patients whose cancers are not clearly "monogenic." In

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addition, educational handouts entitled "Genetics of Breast Cancer," "Genetics of Colon Cancer, " and "Why a Genetic Counselor?" were designed to better meet the needs of the specific patient/physician population we support. Future educational materials will be targeted at the hematological cancers and genetic counseling for patients with average risks. Predictive Value of Microsatellite Instability Screening for Counseling Families with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) J. Graham, E. Martin, T. Prior, A. Isa, R. Chadwick, J. Westman, and A. de la Chapelle James Cancer Hospital and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210 Identification and counseling of families with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) traditionally has relied upon clinical pattern recognition utilizing the "Amsterdam" criteria. Recently, microsatellite instability (MSI) has been postulated as a laboratory technique to identify at-risk kindreds. We examined tumors from 12 unrelated patients with family histories consistent with either strict Amsterdam criteria (group A), relaxed Amsterdam criteria (group B), or early-onset disease (group C). Tumors were scored with a panel of 12 microsatellite sites, i.e., 11 dinucleotide repeat markers and one for the more sensitive mononucleotide BAT-26 marker. DNA from all 12 patients underwent sequencing of all exons, exon-intron boundaries, and the promoter regions of MSH2 and MLH1:

Criteria

MSI (11 loci)

MSI BAT-26

1 2

A A

+

+

3

A



4 5 6 7 8

A A A A B

— _ —

— +

— —

— — — —

9 10 11 12

C C C C

— + _

— + _





Patient

Mutation No mutation identified Stop signal— CAG (Gln) to TAG (stop) in exon 9 of MSH2 Missense— Lys to ala in exon 16 of MLH1 Missense— Ag to Glyn in exon 17 of MLH1 Missense— Glu to Lys in exon 3 of MLH1 No mutation identified Missense— Ala to Pro in exon 12 of MSH2 No mutation identified Stop signal— An insertion at nucleotide 49 of exon 6 of MLH1 stop at (AA171) No mutation identified No mutation identified No mutation identified No mutation identified

Only two tumors (17%) demonstrated MSI by conventional repeat testing. With the more sensitive BAT-26, three tumors (25%) scored MSI positive. Although MSI was present using both methods, no mutation was identified in Individual 10. The mismatch repair deficiency of this tumor may be due to mutations in other genes then MSH2 or MLH1, or to epigenetic factors. Neither MSI nor a mutation was found in three individuals (1,5,7) meeting Amsterdam criteria. A total of six mutations were identified, two within the same person. The frame-shift and stop codons identified in patients 2 and 8 are considered deleterious. A discrepancy exists between the MSI and sequencing results for Individual 8 that may be the result of initial analysis of a tumor block with primarily normal tissue. MSI testing of further samples is designed to clarify this issue. In two individuals (3 and 6), conventional MSI and BAT-26 were negative in the presence of a missense mutation. The four missense mutations will be carefully

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evaluated for genotype/phenotype correlations in the families to assess their potential diseasecausing properties. Genetic counselors are urged to be cautious in the use of MSI determination as the sole basis for pre-screening families considering molecular testing for HNPCC. Appraisals of Controllability Among Women Tested for a BRCA1 Mutation H. A. Hamann, R. T. Croyle, K. R. Smith, B. J. Baty, V. L. Venne, J. McDonald, and J. R. Botkin University of Utah, Salt Lake City, Utah 84112 In Lazarus and Folkman's transactional model of stress and coping, cognitive appraisals are integral to both emotional coping strategies and behavioral responses to situations. A cognitive appraisal is defined as the process of both categorizing an encounter with respect to personal well being, and evaluating what can be done about it (Lazarus & Folkman, 1984). The degree of perceived control in a given situation is an important factor in the process of cognitive appraisal. This study examined perceptions of control for both breast and ovarian cancer among women tested for a family-specific mutation in BRCA1. Participants included 135 females from a Utah-based kindred of Northern European descent who received BRCA1 counseling and test results from a genetic counselor as part of a larger study of the effects of BRCA1 testing. Of the study participants, 52 tested positive for the kindred-specific BRCA1 mutation, and 83 tested negative for the mutation; the ages of the participants ranged from 18 to 78 years (M = 45.6). Study participants were interviewed by telephone both prior to genetic counseling and testing, and also 1-2 weeks after receiving genetic test results. During both interviews, participants were asked to indicate the degree to which they could modify their risk of breast and ovarian cancer, respectively. Paired sample t-tests were performed to compare appraisals of breast and ovarian cancer controllability for mutation carriers from the baseline pretesting measurement to the 1-2 week posttest follow-up. Paired sample t-tests for the same measures were also performed for noncarriers. Independent sample t-tests were performed to compare the changes in controllability appraisals (as calculated from pretest to posttest change) between carriers and noncarriers. Results of these analyses show that neither carriers nor noncarriers showed significant changes in their appraisals of breast cancer controllability from the pretest to posttest measurement. However, while noncarriers also showed no significant differences in ovarian cancer controllability, carriers perceived ovarian cancer as significantly more controllable after testing than before testing (p = .03). In addition, change scores indicated that mutation carriers were significantly more likely than noncarriers to perceive an increase in ovarian cancer controllability from the pretest to posttest measurements (p = .05). One possible interpretation of these results relates to the posttest counseling for carriers and noncarriers; carriers have surveillance and prevention emphasized, while noncarriers are informed that their ovarian cancer risk is not increased and surveillance is not recommended. This difference in counseling content may influence the controllability appraisals of the participants. A second interpretation focuses on a process of psychological minimization in which mutation carriers downplay the threat of ovarian cancer to modulate their emotional reactions to the news of a positive test result. These two interpretations are not mutually exclusive; it is possible that they interact as possible explanations of the study results. A Comparison of Hereditary Cancer Program Models; Genetics-Based vs. Surgery/OncologyBased K. B. Huelsman, G. Rosenthal, and M. K. Dabney Division of Human Genetics, Children's Hospital, Cincinnati, Ohio 45229 In response to increasing patient and professional demand, new hereditary cancer programsi of varying models are developing. Programs are based within the context of compre-

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457

hensive cancer centers, departments of human genetics, surgical departments, and private oncology groups. These programs differ in the emphasis placed upon research, clinical application, and community outreach. There are inherent advantages and disadvantages to each type of program. Genetic counselors initiating new programs should be aware of these factors in order to develop the optimal program matched with the community needs and resources. The authors are genetic counselors who have developed clinical hereditary cancer programs using two different models. For the genetics-based and surgical-based models, the following were compared: setting, counseling protocol, interaction with multidisciplinary team, research endeavors, referral source, indication for counseling, and testing uptake. For each program, data were reported from the most recent year of clinical operation, 3/1/97-2/28/98. During this time period, the genetics-based program saw a new patient volume of n = 133. Of these, 70.7% were referred by a physician. Physician referrals by specialty included: Oncology (31.9%), OB/Gyn (24.5%), Primary Care/Internal Medicine (13.8%), Surgery (8.5%), and others. Overall, 69.1% of patients were referred for history of breast or ovarian cancer. Other patients were referred for consideration of a variety of other cancer syndromes. The genetics-based program data were compared with data over the same time period from a well-established surgery/oncology-based program, which had a clinical patient volume of n = 71. Among patients seen in the surgery/oncology-based program, 83.1% had a physician referral. Physician referral sources included: Surgery (37.3%), Oncology (32.2%), OB/Gyn (10.2%), Primary Care/Internal Medicine (5.8%), and others. The primary reason for referral was hereditary breast/ovarian cancer with nearly 100% of patients referred for this indication. Testing uptake was fairly high in both programs with 46.6% and 53.5% of patients choosing to have genetic testing in the genetics and surgical/oncology programs, respectively. Notably, the uptake rate among Ashkenazi Jewish patients was significantly higher, with an uptake rate of 2 to 3 times that in non-Ashkenazi patients. Data form the first year of a newly established surgery/oncology-based program will be described in order to evaluate differences relating to time since program establishment. Trends in referral pathways and potentially untapped referral sources in each program will be noted. Problems encountered with billing, reimbursement, institutional politics, and clinical supervision will be discussed. Recommendations for program development and strategies to avoid these obstacles will also be addressed. As new programs continue to develop in smaller, less comprehensive settings, the importance of maintaining critical components of genetic counseling in any setting must be stressed. Information from this comparison study will allow genetic counselors to position themselves to effectively maintain leadership in new program development within a variety of settings and disciplines. Evaluation of Factors that Determine the Uptake of Genetic Counseling and Testing for the APC I1307K Mutation K. A. Johnson, J. D. Brensinger, L. S. Rosenblum-Vos, G. M. Petersen, F. M. Giardiello, and C. A. Griwin The Johns Hopkins University, Baltimore, Maryland 21287 The APC I1307K gene mutation is associated with increased colorectal cancer (CRC) risk in the Ashkenazi Jewish population (Nature Genet 17:79, 1997). Testing for this mutation has been available clinically at the Johns Hopkins Hospital since September of 1997, with genetic counseling being a required part of that testing process. The purpose of this study was to evaluate factors that may predict the uptake of the APC I1307K mutation testing or test outcome. To do this, we analyzed data on sex, age, and the family and personal history of those patients seeking counseling at the Johns Hopkins Colon Cancer Risk Assessment Clinic (n = 81), as well as those patients submitting a blood sample to the Johns Hopkins Pathology Molecular Diagnostic Laboratory (n = 219). Of the 81 patients seen at the JHU Clinic, 85% elected testing after the pretest counseling. To compare this rate of testing to the uptake of testing for other cancer predispositions in the clinical setting, we looked at a separate group of JHU clinic patients who were offered testing for HNPCC. Of the 41 patients offered this HNPCC testing, only 17% proceeded. After completing the pretest counseling, 12 indi-

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viduals declined APC I1307K testing. Reasons given for declining testing included: concerns about the effect of testing on the family's insurability (n = 9), recognition that a positive test result would not alter their current CRC screening regimen (n = 3), and complicated family histories where it would be difficult to interpret the test result (n = 2). Those declining testing did not differ in sex or age from those who elected testing. Of the 219 individuals who submitted a blood sample to the JHU lab, 64% were male, the mean age was 55.3 years ± 11.7, 8% had a personal history of CRC, 20% had polyps, and 85% reported a family history of CRC. Test results were available on 215/219 patients, and 23 (10.7%) of those 215 were mutation carriers. Looking at the mutation carriers by personal and family history, we found that 3.8% of those with negative personal and family histories tested positive, 9.1% of those with polyps were positive, 18.8% of those with a personal history of colon cancer were positive, and 20% of those with colon cancer and a family history of colon neoplasia carried the APC I1307K mutation. We conclude that the uptake of testing for the APC I1307K mutation is high, with significantly more men than women pursuing testing and counseling. The previously reported association between the APC I1307K mutation and colon cancer risk was supported by this study's finding that those patients with a personal or family history of colon cancer or polyps were more likely to carry the gene mutation than those without. Cancer Surveillance Behaviors and Risk Perception Among Genetic Counselors and Nurses Providing BRCA1 Testing S. A. Kleffer, K. A. Schneider, J. E. Stopfer, K. A. Calzone, A. F. Patenaude, K. Kalkbrenner, B. L. Weber, and J. E. Garber Dana-Farber Cancer Institute, Boston, Massachusetts 02115 Traditional genetic counseling rarely requires providers to discuss a condition for which they are themselves at risk. In contrast, in predisposition testing for more common adult-onset disorders, providers are likely to have a more personal experience with the disease or be at risk themselves. We had the opportunity to explore this phenomenon in a BRCA1 testing program done in collaboration with the University of Pennsylvania. In this program, we trained nurses (RN) and genetic counselors (GC) to provide the counseling and education for individuals having BRCA1 predisposition testing. Seventy-two GCs and 71 RNs completed questionnaires at baseline and 1-year posttraining regarding demographic characteristics, their own cancer screening behaviors, and attitudes toward predisposition testing for breast/ovarian cancer susceptibility. At baseline, 18 (25%) GCs were currently providing cancer risk counseling, four of whom focused primarily in this area. Forty-five RNs (66%) had worked or were currently working in oncology. Nurses were older (mean age 40; range 23-64) than genetic counselors (mean age 35; range 25-56). Eighty-two percent of GCs and 87% of RNs had a family member or close friend with cancer; seven RNs had had cancer themselves. At both baseline and follow-up, more RNs (baseline 29%, follow-up 30%) than GCs (baseline 10%, follow-up 5%) estimated their lifetime cancer risk above 33% (p < 0.05). Cancer worry was assessed on a 10-point Likert scale where 1 = not at all worried and 10 = extremely worried. Both groups worried about developing cancer to a similar extent at baseline (GCs mean 4.2; RNs mean 3.7) with similar response at follow-up. RNs (99%) were more likely to report performing monthly breast self-examinations (BSE) than GCs (81%) at baseline (p = 0.001). The difference disappeared on follow-up, with an increase in GCs reporting BSE performance. Both provider groups were asked if they would consider having BRCA1 testing themselves. At baseline, more RNs (56%) than GCs (32%) said they would consider testing (p = 0.015). At follow-up, interest of the RNs had declined to 34%; GC interest had declined slightly (25%). GCs and RNs were then asked which medical options they would choose if they had a BRCA1 mutation. No differences were noted at baseline or follow-up between the two groups in the frequencies with which they would consider chemoprevention or prophylactic mastectomy; or having more frequent physician visits, mammograms or transvaginal ultrasounds. At follow-up, more GCs (24) than RNs (19%) would consider prophylactic mastectomy (p < 0.05). There was no significant difference between the groups at baseline (GCs =

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459

28%, RNs = 23%). Consideration of prenatal diagnosis for BRCA1 mutations was higher among RNs than GCs at baseline (32% vs. 6%; p < 0.05) and follow-up (24% vs. 4%; p < 0.05). There was no significant change in the choices of medical options from baseline to follow-up in either group. These data suggest that knowledge and experience gained in the context of professional preparation may influence attitudes and health behaviors among health professionals. An Experimental Study Exploring Factors Associated with Cancer Risk Perception and Delay of Cancer Risk Counseling P. Levonian, W. Bushman, and B. Morgan Gundersen Lutheran Medical Center, La Crosse, Wisconsin 54601 The rapid increase in research on genetic links to hereditary cancer, in particular the identification of BRCA1 and BRCA2 mutations as genetic markers for breast cancer risk, has greatly increased referrals for cancer risk counseling (CRC). Our center and numerous others have noted that patient uptake for CRC has not been as high as might be expected from epidemiological studies. In particular, once referred, some patients appear to be "indefinite deferrers" of initiating CRC. While clinical studies have been done on factors associated with breast cancer treatment and counseling, these generally focus on the amount of time women "delay" treatment for breast cancer. Furthermore, there are few experimental studies and no studies that have specifically addressed the factors influencing delay in following through with CRC. This study used scenarios to examine the impact of a primary care provider's advice on breast cancer risk perception and timing of initiating genetic counseling. Additionally, it manipulated the relatedness of an affected relative to explore respondents' understanding of inherited breast cancer components. Participants were 71 female undergraduates in the age range of 18-22 who presented no history of mothers and/or sisters with a breast cancer diagnosis. Participants completed a questionnaire regarding their own health, health attitudes, and family history and then read a factual one-page handout detailing risk factors that influence the occurrence of breast cancer. The handout focused on identifying risk factors for heritable breast cancer. After reading the handout, participants were asked to place themselves in a medical scenario where they are a healthy young woman with a mother (or grandmother) who was diagnosed with breast cancer at the age of 37. The doctor gives one of two kinds of advice: an urgent comment "Frankly, given your history, I have some concerns about your breast cancer risk. I'd like for you to make an appointment with a genetic counselor in the near future" or a less urgent comment "Frankly, I'm not overly concerned about your family history, but I'd like you to have an appointment in the near future with a genetic counselor to discuss your breast cancer risk." This 2x2 design focused on two central dependent variables: perception of breast cancer risk and delay of follow-up. The results yielded fewer significant effects than expected. In particular, there were no interaction effects. Of note were two significant findings. First, as expected, having a mother affected in the scenario was related to higher breast cancer risk perception (M = 1.80 on a 5-point scale where 1 = "much higher than average risk") than was having an affected grandmother [(M = 2.15), F(l,65) = 6.06, p = .01]. Second, as expected, the strength of the primary care provider's advice affected respondents' reports of how soon they would make an appointment with a genetic counselor (as measured in days). The more urgent advice yielded a lower number of days until calling for an appointment (M = 7.78); whereas the less urgent advice yielded a higher number of days [(M = 16.82), F(l,63) = 2.68, one-tailed p = .05]. Finally, although not statistically significant, the primary care provider's advice appeared to have an effect on perception of breast cancer risk (on a 7-point scale), where the less urgent advice led to a lower perception of risk (M = 5.38) than did the more urgent advice [(M = 5.72), F(l,65) = 2.30, p = .13]. The relatedness and advice manipulations had no effect on respondents' level of anxiety or their overall likelihood of making an appointment with a genetic counselor (both rated on 7-point scales). In general, even in this young population, risk perception responses were highly skewed toward more "drastic" appraisals of risk. Given the relatively few empirical experi-

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Issues in Cancer Genetics Abstracts

mental designs employed within the genetic counseling literature, this study suggests that scenario manipulations may be of help to health professionals. In particular, the way a primary care provider phrases his/her advice may have an impact on a patient's affect and mood. In this study, we were disappointed to see that the manipulation of the relatedness of the affected relative did not yield larger results. More research is needed to see whether or not respondents truly understood the factual information they were provided. Overall, this study begins to examine factors that may have a significant impact on patients' understanding of genetic information and their subsequent behavior. Hereditary Prostate Cancer: Potential Challenges Facing Genetic Counselors from a New Population of Clients L. M. Lucas, K. A. Brooks, S. R. Young, and S. P. Weinrlch University of South Carolina, Division of Genetics, Department of Obstetrics and Gynecology, Columbia, South Carolina 29203 Prostate cancer has long been recognized as having a strong familial etiological component. In recent years, scientific advances have vastly increased the understanding and knowledge concerning the hereditary nature of some cases of prostate cancer. A potential prostate cancer susceptibility gene was localized in 1996 to chromosome 1 which spawned great interest and excitement in the growing field of cancer genetics. As the genetic characteristics of prostate cancer become clearer, genetic counselors may face an increase in demand from high-risk families for information regarding cancer genetics, risk assessment, screening, and prevention methods, and the potential for presymptomatic susceptibility testing. As the vast majority of those in the genetic counseling profession are female, gender-biases, and differences between the counselor and the client must be addressed in order for the client to receive the highest quality of care and services. The purpose of this investigation was fourfold: (1) to explore the current status of knowledge of genetic counselors regarding hereditary prostate cancer; (2) to determine the extent of their experience in dealing with prostate cancer; (3) to assess the attitudes of genetic counselors towards the potential influx of male clients; and (4) to evaluate perceived gender differences as they relate to the cancer genetic counseling process. A survey was distributed to 400 participants of the cancer genetics short course of the 16th Annual Education Conference of the NSGC. Analysis of the responses indicated that genetic counselors, overall, report being somewhat familiar with recent advances in prostate cancer genetics, and most counselors anticipate an increase in demand for genetic counseling services as research progresses. A majority of genetic counselors expressed interest in counseling for hereditary prostate cancer; however, concerns were expressed in their level of comfort with many sensitive issues including sexuality and screening modalities. Female clients were rated by the responding genetic counselors as stronger in their knowledge of family history, willingness to discuss emotional issues, and their level of comfort with the discussion of topics of a sexual nature. Additional challenges indicated by respondents included a greater need for education regarding screening methods, prevention, and male psychosocial issues, difficulty in obtaining an accurate family history, and a general lack of comfort on the part of male clients. Overall, however, genetic counselors reported an interest and willingness to pursue this emerging area of genetics, and by recognizing the gender biases, would be capable of delivering high-quality services to this potential new population of clients. Cancer Risk Counseling: An Educational Perspective

A. E. Lundgren University of Maryland Medical Center, Baltimore, Maryland 21201 Cancer risk counseling has rapidly become an important subspecialty within the field of genetic counseling. A clear understanding of cancer genetics, clinical oncology, current sur-

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461

veillance recommendations, cancer prevention and treatment, and risk assessment are among the skills imperative for cancer risk counselors. The increased demand for cancer risk counseling services and the complexity of the service offered made adequate training of genetic counseling students necessary. A survey was distributed to all 26 Master's level genetic counseling programs to assess the degree of cancer genetics and cancer risk counseling training. Twenty-two of 26 program directors replied (85%). Twenty-three percent of the respondents currently offer an entire course devoted to cancer genetics and cancer risk counseling. The majority of responding programs, 77%, include cancer genetics training in lectures within a basic genetics course, and 68% include cancer training in lectures within a genetic counseling course. Thirty-two percent of responding programs provide cancer genetics training in the form of workshops or short courses outside of specified classes. In addition, some programs offer training and experience through case presentations, journal clubs, and departmental conferences. Ninety percent of responding programs provide students with the opportunity to gain clinical experience in cancer risk counseling, though the clinical setting varies. Sixty-four percent of programs plan to add more extensive cancer training to the curriculum. A second survey was sent to NSGC cancer SIG members currently providing cancer risk counseling. The purpose of the survey was to obtain information about professional experience prior to performing cancer risk counseling, cancer genetics training in graduate school as well as recommendations for the current curriculum offered by Master's level training programs. Ninetytwo of 138 replied (66%). Thirty-two percent of respondents had 1 year or less experience prior to providing cancer risk counseling. Twenty-two percent had between 2-3 years of experience prior to providing cancer risk counseling, and 11% had between 4-5 years of experience. Combined, 65% of respondents had 5 years or less experience in other areas of genetic counseling before performing cancer risk counseling. Forty-six percent of respondents report receiving cancer genetics and/or cancer risk counseling training in their genetic counseling training program, while 54% report receiving no training in cancer genetics or cancer risk counseling. The vast majority of respondents report attending workshops and short courses for continued education in cancer genetics and risk counseling. Ninety-two percent of respondents feel that genetic counseling training programs need to incorporate more cancer specific in the curriculum. When asked to recommend ways to incorporate more cancer specific training, an overwhelming 93% of respondents recommend more clinical training. Fifty-three percent of respondents recommend adding a full-term course that includes cancer genetics and cancer risk counseling. Additional findings will be presented in the poster. This study provides insight for program directors responsible for creating and updating training curriculum. Predictive Value of Family History (FH) in High Risk Breast Cancer (HRBC) Patients Treated with High-Dose Chemotherapy (HDCT) D. J. MacDonald, G. Somlo, A. Ostrovsky, S. Sand, T. G. Krontiris, and J. N. Weitzel City of Hope Comprehensive Cancer Center (COHCCC), Duarte, California 91010 Identifying women at increased risk for breast and ovarian cancer could result in detection of cancer at an earlier, more curable stage. Up to 10% of breast cancer (BC) and ovarian cancer (OC) may be due to mutations in highly penetrant genes associated with heritable cancer syndromes. An important feature of hereditary cancers is earlier age at onset. The median age of >300 HRBC patients treated with HDCT at the COHCCC between 198997 is 42 years (95% £ age 55) compared to the median age of 57 for unselected breast cancer cases. In order to identify persons in whom FH suggests a genetic susceptibility, and to determine the contribution of inherited mutations to clinical outcome (phenotype and prognosis) in HRBC patients, we are obtaining detailed FH and blood samples for DNA analysis. To date, information on 48 women has been obtained. Two empiric breast cancer risk estimation models were used to estimate risk: one based on first- and second-degree FH (Claus et al., 1994) and the other based on first-degree FH and reproductive factors (Gail et al., 1989). Thirty-three percent (16/48) of our cohort reported a FH of BC, in contrast to the 6-19% of FH reported by unselected breast cancer patients. Nearly 15% (7/48) had a FH suggesting

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inherited predisposition to BC and/or OC, including a woman with possible paternal transmission. Importantly, 19 of the 21 patients who did not report a FH of either BC or OC had limited family structure. We conclude that the empiric models used to estimate lifetime probability of developing breast cancer were poor predictors of BC risk in this HRBC cohort. Evaluating Outcomes of Counseling and Identification of Individuals at Risk for BRCA1 and BRCA2 Mutations in the Ashkenazi Jewish Population M. Magee, K. Kelly, D. Chowdary, M. Schwalb, D. Toppmeyer, and H. Leventhal Center for Human and Molecular Genetics, University of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103 In an effort to assess and improve the experience of genetic counseling and testing services for individuals at risk to carry BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population, we are conducting a longitudinal study of eligible individuals over 8 months. Specifically, the study examines (1) the changes in knowledge and affect attributable to genetic counseling, (2) the factors that motivate or discourage individuals from testing, (3) the emotional response to test results or the decision not to test, and (4) the changes in health behavior after genetic counseling and testing. Measures include written surveys and telephone interviews and are administered prior to genetic counseling (time 1), 1 day after genetic counseling (time 2), 1 week after results disclosure (time 3), and 6 months after results disclosure (time 4). Those participants who decline genetic testing continue to be included in the study and have their time 3 and 4 assessments performed at time intervals similar to those who elect testing. Our results show a very high acceptance rate for testing, with 48 of the 53 (91%) individuals counseled electing to be tested. Of the 48 individuals tested, ten individuals from six families tested positive for BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT Analysis of the time 1 and time 2 data revealed that after the initial genetic counseling session, distress and depression decreased, knowledge regarding personal and familial risk increased, and knowledge of genetic principles increased. Of interest, the amount of information attained in the initial counseling session was not hindered by the participant's level of distress. Further analysis of the time 3 and time 4 data will reveal the longevity of the knowledge attained during counseling and the impact of test results on participants' emotional well-being, family relations, and health behaviors. Insurance Reimbursement for BRCAI and BRCA2 Sequence Analysis S. A. Manley, R. I. Pennell, and T. S. Frank Myriad Genetic Laboratories, Salt Lake City, Utah Gene sequencing is the most sensitive method for analyzing clinically significant mutations in BRCAI and BRCA2. The passage of Federal law protects women in group insurance plans from discrimination based on genetic test results, but does not guarantee coverage for genetic testing services. We therefore sought to determine the success of individuals seeking insurance reimbursement for BRCAI and BRCA2 analysis. We analyzed outcomes of 186 claims for insurance coverage of gene testing by our reference laboratory submitted between November 1997 and April 30, 1998. One hundred and eleven (60% of the individuals submitted claims indicated a previous cancer diagnosis. Of the 186 tests for which insurance reimbursement was requested, 144 were full sequence analysis of both BRCA1 and BRCA2, one was for BRCAI only, three were for BRCA2 only, three were for family-specific mutations, and 35 were for the three mutations most commonly observed in women of Ashkenazi ancestry. Thus far, 63 claims have been reimbursed and the remainder are still pending. No claims have been denied to date. These data indicate that women who seek insurance coverage for BRCAI and BRCA2 testing services will usually be successful.

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The Knowledge and Attitudes of South Carolina and Georgia Gynecologists Toward BRCA1 and BRCA2 Testing C. Masciangelo, K. A. Brooks, S. R. Young, A. Trepanier, and S. T. Smith University of South Carolina, Columbia, South Carolina 29203 While testing for BRCA1 and BRCA2 mutations has previously been on a research-only basis, it has now made its entrance into the commercial arena. Obstetrician/gynecologists are prime candidates to receive inquiries regarding this testing and, therefore, it is important to determine their knowledge and attitudes regarding BRCA1/2 testing. Therefore, we surveyed a total of 104 gynecologists at a dual-state conference regarding these matters. The survey inquired about whether patients were routinely asked about family history, whether the physicians were comfortable with their knowledge of hereditary cancer syndromes, what they believed the risks associated with carrying a BRCA1/2 mutation to be, what recommendations they would have following testing, as well as what they considered the perceived benefits and concerns of testing to be. A response rate of 33% was achieved. The vast majority of the respondents (91%) were aware of the importance of completing a family history, and did so as a routine part of a new-patient intake. Maternal family history was slightly more likely to be inquired about during this intake than was paternal family history (70% vs. 63%). With regard to the risks associated with carrying a BRCA1/2 mutation, the respondents were more likely to be familiar with the risks of BRCA1 mutations that with the risks of BRCA2 mutations. Nineteen percent correctly identified both breast and ovarian cancer risks for BRCA1 mutation carriers vs. 11% that correctly identified both risks for BRCA2 mutation carriers. Just over half (53%) of the physicians surveyed indicated that they felt comfortable discussing familial or hereditary cancer with their patients. Yet, the majority (76%) reported patient inquiries regarding testing, with 54% of these being referred to genetic counselors and 23% to other physicians. Patients were more likely to proceed with testing following counseling by a genetic counselor or a more specialized physician than if they were counseled by the gynecologist (64% and 67%, respectively, vs. 11%). The respondents felt the most appropriate candidate for testing was a female with a strong family history of breast cancer. Following a positive test result, 33% recommended prophylactic mastectomy and 58% recommended prophylactic oophorectomy. No respondents indicated that chemoprevention would be recommended. All of those that completed the survey felt the testing had both benefits and risks. Overall, there was a fair amount of knowledge regarding BRCA1 and BRCA2 mutations, as well as the controversies regarding testing. This survey does indicate that these physicians are likely to refer individuals to individuals who are more specialized in the field of genetic testing for discussion. Genetic Counseling for Hereditary Breast and Ovarian Cancer. Involvement of Affected Relatives J. C. Narvaez, A. Wonderlick, and B. Fine University of South Carolina, Columbia, South Carolina 29203 BRCA1 and 2 testing for an unaffected at risk individual requires the participation of a relative who has had breast or ovarian cancer in order for the testing to be most informative. Prior to genetic counseling, at risk individuals are often unaware of the need to involve an affected relative, and may express displeasure at the idea of doing so. Studies have not as yet assessed patients' feelings concerning the involvement of affected relatives in genetic counseling and testing for cancer susceptibility, nor have any studies assessed the role of genetic counselors in facilitating contact with family members. The purposes of this study were: (1) to explore patients' reactions to the suggestion of involving an affected relative in BRCA 1 and BRCA 2 counseling and testing, (2) to assess the patient' relationship with the affected relative, (3) to evaluate the patient's feelings regarding breast or ovarian cancer; and (4) to define the extent to which patients desire a genetic counselor be involved in contacting an

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affected relative. A 52-item questionnaire, including the Revised Impact of Events Scale (RIE) (Horowitz et al., 1979) and the Family Satisfaction Questionnaire (FSQ) (Olson and Wilson, 1982), was administered to 22 previously counseled participants through telephone interviews. Women who participated in the study tended to be in their forties (x = 43, SD = 8.62), Caucasian (100%), college educated (77.3%), married (72.7%), and have children (77%). The main variable predicting the preferred means of genetic counselor assistance was the reaction of the participant to learning that the involvement of an affected relative was necessary for genetic testing to be most informative. Participants who expressed positive emotions concerning the involvement of an affected relative were more likely to exhibit a significant impact of thoughts of breast and ovarian cancer on daily activities (lower RIE scores), to indicate more favorable relationships with their affected relative (lower FSQ scores), and to prefer that the genetic counselor either provide written information for relatives or communicate directly with relatives by telephone or correspondence. Participants who reacted negatively to the idea of involving an affected relative were more likely to indicate a greater impact of thoughts of breast and ovarian cancer on daily life (higher RIE scores), to feel more dissatisfied in their relationship with their affected relative (higher FSQ scores), and to prefer that counselors not be directly involved with relatives, but rather roleplay possible conversations with affected relatives during the genetic counseling session. The majority of women (66%) expressed a desire to receive information that they could share with relatives, regardless of FSQ or RIE score. Since the majority of our sample (72%) contacted an affected relative within a week, it seems that it would be beneficial for genetic counselors to develop fact sheets to share with patients at the time of counseling. In addition, these results suggest that genetic counselors should adjust their counseling session based on each patient's reaction to learning that the involvement of an affected relative will be necessary for genetic testing to be most informative for their family. Additional research in this area is necessary in order to further delineate between the differences in women's reactions to the suggestion of involving an affected relative and the implications of these reactions on genetic counseling practices. An Ashkenazi Jewish Man with Germllne Mutations in Both BRCA1 and BRCA2 K. Panabaker, B. McGillivray, S. Adomat, D. Horsman, and C. Kim-Sing B.C. Cancer Agency, Vancouver, British Columbia, Canada Since the identification of two mutations in the BRCA1 gene and one mutation in the BRCA2 gene in the Ashkenazi Jewish population, mutation analysis among individuals in this group is presenting with challenging clinical dilemmas. One such case involves a 60-year-old man of Ashkenazi Jewish descent who has a strong family history of breast cancer in both women and men on his father's side of the family, and a mother who died of premenopausal bilateral breast cancer. He first sought genetic counseling for cancer risk assessment when a paternal family member was shown to carry the BRCA2 6174 delT mutation. Due to his ethnic background and a family history of breast cancer on both sides of his family, mutation analysis for the three common mutations was carried out. The results showed that he carries two germline mutations, specifically the BRCA1 185delAG and the BRCA2 6174delT Other than a few case reports, the current literature discusses cancer risks associated with the inheritance of one inherited mutation in either of these genes. We present this case to illustrate the complexities that followed in communicating such test results to this gentleman and his three adult children, in addition to the associated clinical implications and recommendations for cancer screening. A Pilot Study to Develop and Evaluate a Hereditary Cancer Program K. Panabaker, M. McCullum, B. McGillivray, D. Horsman, C. Kim-Sing, M. Burgess, and W. McKellin B.C. Cancer Agency, Vancouver, British Columbia, Canada

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Since the identification of the BRCA1 and BRCA2 genes, the demand for hereditary cancer risk assessment and susceptibility testing has been substantial. People with a significant family history of breast and/or ovarian cancer may now participate in genetic testing to learn whether or not they have an inherited gene mutation which substantially increases their lifetime risk of developing breast and/or ovarian cancer. They may also choose not to pursue genetic testing. Whatever their decision, individuals from such families may require services and support to deal with the medical and psychosocial implications of their inheritance. 15 prepare for the implementation of a hereditary cancer program, an interdisciplinary group developed a counseling and followup protocol for individuals eligible for genetic testing for hereditary breast/ovarian cancer. The primary objectives of this pilot study are to determine whether the protocol as delivered in the research design: (1) increases participants' understanding of hereditary cancer and the associated risks, (2) avoids severe psychological reactions, and (3) affects self-reports of cancer screening behavior. This paper will describe some of the key issues identified to date through the experiences of participants in the study, and their impact on the development of a comprehensive provincial hereditary cancer program. Attenuated Familial Adenomatous Polyposis in an Adult with a Deletion of the Entire APC Gene R. Pilarski, P. Benn, A. Brothman, and S. Rosengren CT Children's Medical Center, Hartford, Connecticut 06106 Familial Adenomatous Polyposis (FAP) is an inherited colon cancer syndrome caused by mutations in the APC gene on chromosome 5q21. Patients typically present with at least 100 (and usually several hundred to several thousand) polyps throughout the colon. Benign and malignant extracolonic manifestations are often present as well. Seventy-five percent of FAP patients will present with colonic adenomas by age 20, and nearly 95% will present by age 35. The large number of polyps makes the development of colon cancer nearly inevitable. The average age of diagnosis of colon cancer in untreated (noncolectomized) patients ranges between 35 and 43 years in various studies. A variant of FAP (termed "attenuated" FAP) has been recognized in which patients present with under 100 polyps and appear to have a delayed onset of the clinical manifestations of FAP. Most APC gene mutations causing both typical and attenuated FAP are point mutations or small deletions or insertions leading to a premature stop signal and a truncated protein, with mutations in attenuated FAP patients occurring at the extreme 5' end of APD gene. Thirteen patients have been reported in the literature, however, with FAP secondary to germline interstitial deletions of the entire APC gene locus. In all cases (with the exception of a 13-year-old boy who presented with extracolonic manifestations of FAP), polyposis presentation was consistent with typical FAE We now report a mentally retarded 39-year-old male with a cytogenetically visible interstitial 5q deletion, whose polyp presentation is consistent with attenuated FAP. Molecular analysis confirmed that the deletion included the entire APC gene region. This is the first reported case of attenuated FAP associated with a germline deletion of the entire APC gene. The limited prognostic information available for this unique patient fed in to his mother's ambivalence about pursuing prophylactic colectomy, and led to several counseling and ethical dilemmas regarding management decisions for this patient. Family Influence on the Decision to Undergo BRCA Testing T. Powell, S. Jeffrey, and D. Cua Stanford University, Stanford,

California

The primary objective of this research is to examine both the extent and nature of family influence on an individual's decision to undergo genetic testing for breast/ovarian cancer (BRCA testing). My goal is to identify family factors which have an impact on a person's

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attitude toward BRCA counseling and testing. Qualitative research methods are used to explore the dynamics in a family with multiple cases of breast and/or ovarian cancer, including experiences, communications, and relationships. This will help in understanding why there is such a lack of utilization of BRCA testing despite a high degree of interest reported in previous studies. Approximately 50 women who are either (1) diagnosed with breast/ovarian cancer, or (2) at risk for carrying a disease-causing mutation are the participants for this study. These women are from families with at least two female first-degree relatives with one of these cancers. Effort is made to include multiple members of each family. Methodology for this study includes (1) a demographic questionnaire, (2) in-depth interviews with open-ended questions, and (3) descriptive analysis of both questionnaire and interview. The short answer questionnaire will assess individual and family history of breast/ovarian cancer, personal experience with genetic cancer and genetic testing, breast/ovarian cancer health care practices, and important sources of information. In the interview, participant's describe their personal and family experiences and interactions concerning inherited breast/ovarian cancer and how they arrived at their genetic testing decision. Preliminary results indicate that family relationships and the denial associated with cancer by family members can have a negative impact on an individual's decision to undergo BRCA testing. These factors can lead to a lack of family disease history knowledge and involvement in the cancer experience of their family member, which are found to be important in whether a woman believes genetic testing is appropriate for herself and her family members. Additionally most participants believe in a combination of lifestyle and genetic causes for the cancer in their family members. Healthy lifestyle decisions and diligence about cancer screening are believed to counteract the genetic defect. The conclusions from the study will be relevant to genetic counselors and physicians who provide healthcare for patients from families with multiple cases of breast and/or ovarian cancer. Additionally, this study can aid in developing genetic testing protocols and for assessing the counseling needs of all family members. The Family Cancer Program Database K. Regan, K. Johnson, D. Kreimer, M. Peedin, and J. Schildkraut Duke University Medical Center, Box 2949, Durham, North Carolina 27710 The Duke Family Cancer Program (FCP) database was developed over a 2-year period to meet the direct needs of a BRCA1/2 genetic counseling study and to provide a resource for the management of future familial cancer studies. The FCP database addresses the complexities of studying inherited cancer syndromes. Data associated with tracking families over time, obtaining informed consent for participation in multiple studies, and ascertaining epidemiologic risk factors are tracked using a relational client/server database with an objectoriented front end. The database was designed to support multiple users of different capacities. The FCP database incorporates a generic, modular design structure for storing familial cancer data with the flexibility for incorporating new studies. Many studies require specialized program considerations such as randomization schemes, probability calculations, or tailored material algorithms. The FCP database provides the ability to incorporate these programs into the database structure. Interfaces to other systems such as the Duke University Tumor Registry are provided through customized interface development. The use of industry standard database development tools and communications protocols allows for each construction of user interfaces. Output to Cyrillic and SAS are also provided. The FCP database will be presented in the context of a university-based genetic counseling study to illustrate the utility of such a tool for organizing familial data and tracking complex projects. Given the confidential nature of this and other familial studies, security was our main concern as we developed this database. In addition, in studies with the participation of multiple family members, it is critical to have a system for organizing data from multiple sources. The best possible family history data is obtained in order to provide accurate risk estimates in counseling. The FCP database was created to manage the multiple steps involved in the process of obtaining and verifying this data. Specific features to be presented include the following:

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• •

Technical specifications and security model. Data driven survey engine: repository for existing and future behavioral and epidemiologic research surveys. • Event log: an advanced mechanism for event flow management (scheduling and rescinding of an event is based on completion or cancellation of a previous event). • Management of diagnosis confirmation process. • Genetic counseling screen: for tracking counseling-related events such as blood draw, testing decision, and encrypted test results storage. • Database interface link to BRCAPRO Probability Calculation Model (calculates the probability of being a BRCA1/2 carrier). • Pedigree reconciliation: requires resolution of conflicts in data from several sources (proband's reported family history, pathology reports, physician reports) and provides confidential pedigree views for family member privacy. • Pedigree drawing: exports to Cyrillic. • Custom reporting and SAS output for ad hoc reporting. Decisions About Prophylactic Surgery Following BRCA1/2 Results K. A. Schneider, D. Schrag, S. A. Kieffer, K. E. Shannon, T. Light, L. DiGianni, K. Kalkbrenner, and J. E. Garber Dana-Farber Cancer Institute, Boston, Massachusetts 02115 Women who receive a positive BRCA1/2 result are given the option of surgically removing their breasts or ovaries as a way of substantially reducing their cancer risks. There are both medical and emotional consequences of having prophylactic surgery and residual risks of cancer remain. A total of 104 women have received BRCA1/2 test results through the research predisposition testing program at our Institute, with 37 women receiving positive results. We were interested in exploring variables that might help predict which women would choose to have prophylactic surgery. We specifically looked at interest in surgery at baseline, recommendations from personal physicians, demographic variables, and personal or family history of cancer. We focused on women who met the following criteria: (1) they had received positive results; (2) they had received results at least 3 months earlier; and (3) they had the option of PO or PM (i.e., had not had bilateral oophorectomy or mastectomy prior to testing). There were 26 women who had the option of PO at baseline and 28 women who had the option of PM. Within 9 months of receiving positive BRCA1/2 results, 11/26 (42%) women underwent PO and 3/28 (11%) had PM. One of these women had both procedures. First, we looked at baseline interest in testing and physician recommendations. Eighty percent of women having PO had said at baseline that they would "consider having PO" and also that their physicians had recommended it. Of women who did not have PO, 21% had said they would consider it and 20% said their physicians had recommended it. Sixty-seven percent of women having PM after learning their results said at baseline that they "would consider PM" and 33% said that their physician had recommended it. Of women not having PM, none had considered it prior to testing and none of their physicians had recommended it. Comparison of demographic variables, including age, marital status, number of children, level of education, and household income, did not reveal any differences between women who did have prophylactic surgery and those who did not. Lastly, we looked at the influence of personal and family histories of cancer. Many of the women with positive results had been diagnosed with cancer prior to having BRCA1/2 testing; 16 had breast cancer, three had ovarian cancer, and four had both breast and ovarian cancer. Thirty-six percent of women having PO and 67% of women having PM were breast cancer survivors, Interestingly, none of the women with ovarian cancer elected to have PM. Many women reported having close relatives who were diagnosed with cancer. Seventh-three percent of women having PO had a mother or sister diagnosed with ovarian cancer compared to 40% of women not having PO. All of the women with PM

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had a first-degree relative diagnosed with breast cancer compared to 36% of women who did not have PM. None of these differences were significant. The one woman who had both PO and PM had never had cancer herself, but her mother had died from breast cancer. This exploratory study suggests that women are not rushing to have prophylactic surgery after learning they carry a BRCA1/2 mutation. The decision to have surgery appears to be highly personal and is based on more than a single factor. Genetic counselors, who are experienced in helping individuals weigh risks and benefits, may be able to help facilitate this decision-making process. Reporting WT1 Gene Frequency to Mothers of Wilms Tumor Patients: The Value of Genetic Counselor Follow-up K. E. Shannon, A. F. Patenaude, G. Chang, J. Morgan, L. Oilier, and F. P. Li Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts 02114 Wilms Tumor (WT) is a tumor of embryonal kidney cells. It has an incidence of 1/10,000 and is one of the most common solid tumors in children, with approximately 80% of cases diagnosed under age 5. Only rarely is WT inherited. Little attention has been given to education WT families about the recent advances in the understanding of the molecular genetics of WT In a study of 200 WT patients, we found that 4% harbored a germline mutation in the WT1 gene. A pilot study was undertaken to investigate attitudes and understanding of genetic information among participants' mothers. The study consisted of completing demographics, attitudes, and knowledge questionnaires before and after receiving written educational materials. Educational materials included (1) a letter describing the overall results of the study with an explanation that individual results were not available, and (2) a WT Fact Sheet that provided general information about genetic testing for WT1. After completing the posteducation set of questionnaires, participants were interviewed by a genetic counselor via telephone to assess patient satisfaction and understanding of the aggregate results. These interviews were structured and audiotaped with participant consent. Fifty-five of the original 200 participants were selected at random and permission to re-contact their mothers was obtained from the child's referring physical 30/55 posteducation questionnaires were returned. 26/30 agreed to participate in the telephone interview. Eighty-five percent of participants contacted reported that they found the WT Fact Sheet helpful in understanding the genetics of WT However, 58% of participants had specific questions that needed to be addressed by the genetic counselor. An additional 27% asked for clarification when the information in the fact sheet was reviewed. When asked whether or not they desired individual WT1 testing for their child, 60% of participants indicated that their child should make his/her own decision when he/she reached childbearing age; 20% of mothers reported they wanted their child individually tested; and 35% of the participants interviewed reported strong emotional responses to the disclosure letter and fact sheet which ranged from fear to relief. One participant reported being "frightened" by reading the fact sheet and two reported overwhelming worry that their other children would develop WT Two mothers reported extreme frustration that individual or complete test results were not available for their child. Four mothers reported overwhelming feelings of relief that they were unlikely to have caused their child's WT These women reported that they had experienced feelings of guilt that they had done something wrong during their pregnancy which resulted in their child's cancer. These women all reported feeling more reassured and accepting of the information after the phone discussion with the genetic counselor. Our study suggests that using written educational materials on genetics and genetic testing may be helpful, but should be used in conjunction with genetic counseling which can provide more detailed explanation and reassurance. Identification of Decision-Making Factors and Barriers to Genetic Counseling in Women with a Family History of Breast Cancer

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W. Sternitzky, K. Huelsman, E. Lower, H. Saal, and G. Yager University of Cincinnati, Cincinnati, Ohio 45229 In order to better understand the genetic counseling needs of women at risk for hereditary breast cancer, a study was initiated to describe the characteristics of women with family histories of breast cancer who choose and do not choose to present for genetic counseling. This information can help identify decision making factors and barriers which affect participation in genetic counseling. Subjects for the noncounseling group were recruited from two sources—a family history questionnaire received from 118 patients seen at The Barrett Cancer Center, and through the telephone intake records of The Hereditary Cancer Program. The patients met the family history criteria and were offered genetic counseling, but did not schedule an appointment. Between the two sources, a total of 131 subjects were included in the noncounseling group. Subjects were mailed a questionnaire which assessed demographics, genetic counseling decision making factors, attitudes about genetic testing, risk perception, and knowledge of hereditary cancer. Seventy (53%) subjects responded to the questionnaire. Because the noncounseling subjects were recruited from two different sources, data from the two groups were analyzed separately to determine if there were differences in subject source before combining them into a single noncounseling group. The factors ranked most important in deciding to see a genetic counselor were: (1) to learn about risks for family, (2) to learn more about cancer, and (3) curiosity. The factors ranked least important in deciding to see a genetic counselor were: (1) making time for another appointment, (2) family's support of decision, and (3) discussing experiences with cancer. Noncounseling subjects appeared to be more interested in the educational components of genetic counseling rather than the psychosocial aspects. The noncounseling subjects also appeared to misinterpret the context of the word "counseling" and were not interested in having counseling in the traditional sense. Designing educational materials which emphasize the information-giving component of genetic counseling and avoid the use of the term "counseling" may increase participation. A comparison was conducted within the noncounseling subjects to determine if there was a relationship between their plans to seek genetic counseling at sometime in the future and their likelihood of pursuing genetic testing. Subjects who thought they were likely to pursue testing were significantly more likely to include genetic counseling (p = value < 0.05). This indicates that the subjects did perceive genetic counseling to be a necessary part of the testing process. In order to determine more accurately the risk of having a BRCA1 or BRCA2 mutation for the subjects in the noncounseling group, the family history information was assessed using three models: Couch et al. (1997), Frank et al. (1998), and Shattuck-Eidens et al. (1997). The mean likelihood of mutation for the subjects recruited through the telephone records and the subjects recruited through the family history questionnaire were 33.5% and 19.0%, respectively. This demonstrates that many women with significant risks for hereditary breast cancer are not being identified or referred for genetic counseling. Genetic counseling may be especially beneficial for moderate risk women since their family histories are less dramatic, and they may be less aware of their risks and screening options. Data from subjects presenting for genetic counseling will be analyzed similarly and compared to the noncounseling group in order to identify differences between women seeking counseling and those who do not. The results of this study will help genetic counselors to anticipate questions and priorities of those calling to inquire about cancer risk and assessment and to facilitate better utilization of genetic services. This information can also help genetic counselors develop educational materials which address potential barriers and make genetic counseling accessible to more women. The Utility of FISH in Detecting Maternal Cell Contamination in Chorionic Villi Samples and the Need for Genetic Counseling S. A. Aufox, M. N. Berry, D. Marnane, T. H. Stamper, S. Robertson, K. Cox, B. Jackie, P. N. Rao, and M. J. Pettenati

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Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 Chorionic Villi Sampling (CVS), a prenatal testing option in which fetal tissue samples are obtained, can be used to diagnose genetic conditions during the first trimester of pregnancy. The major advantage that CVS has over other prenatal testing options, such as amniocentesis, is the ability to perform genetic testing earlier in pregnancy. A disadvantage of CVS, compared to other forms of prenatal testing, is the increased potential for maternal cell contamination (—1-2% of cases), which can cause in an incorrect or uninterpretable result. Fluorescence in situ hybridization (FISH) has been quickly gaining usage in regard to providing rapid molecular cytogenetic analysis on prenatal samples. FISH offers an initial, quick diagnosis of the aneuploidies involving chromosomes 13, 18, 21, X, and Y. The Wake Forest University School of Medicine's Cytogenetic and Molecular Cytogenetic Laboratory has been utilizing FISH on uncultured interphase cells (direct analysis) to determine the presence of maternal cell contamination on all CVS samples. FISH aneuploidy analysis has been performed on CVS samples by physician request since 1995. Tb date, 26 cases had direct FISH screening to evaluate for maternal cell contamination. Each CVS sample was thoroughly cleaned according to clinical laboratory procedures and examined by two separate individuals. Maternal cell contamination was defined as those cases in which there were discrepant results from FISH and/or cytogenetic analysis. Maternal cell contamination was detected by FISH in four (4/26) CVS cases. In cases 1 and 2, FISH on uncultured CVS samples identified both Y bearing cells and cells that were XX in origin. In both of these cases, cytogenetic analysis identified 46,XY metaphases. Because of the detection of Y bearing cells an XX cells by FISH analysis and the 46.XY cells identified by cytogenetic analysis, the XX cells detected by FISH were thought to be due to maternal cell contamination. In cases 3 and 4, FISH reported the presence of Y bearing cells, however, cytogenetic analysis identified only 46.XX cells. In case 3, FISH with X and Y probes detected only Y bearing cells. Cytogenetic analysis identified only 46.XX metaphases in 20 cells. Because of the FISH results, additional cells (130) were analyzed and a single 46.XY cell was identified. An amniocentesis was performed and cytogenetic analysis revealed a 46.XY karyotype. In case 4, the father was known to carry a balanced 3;18 translocation, FISH showed that 98% of the cells were Y bearing while 2% were XX in origin. Based on FISH analysis, it was determined that maternal cell contamination was present. Cytogenetic analysis of 20 cells showed a 46.XX chromosome complement. Further analysis of 80 cells were performed because of the FISH results and revealed two cells which were XY in origin. The two XY cells detected also contained the /(3;18) inherited from the father. If FISH had not been performed for maternal cell contamination in cases 3 and 4, a misdiagnosis would have occurred. In cases 3 and 4, both couples chose the option of CVS because of a family history of a chromosome anomaly and for the option of obtaining cytogenetic information as early as possible in the pregnancy. In both cases, the family histories in conjunction with the conflicting results from FISH and the completed cytogenetic analyses posed challenges to the genetic counseling session. The detection of maternal cell contamination can help eliminate the potential of misdiagnosis only in those cases in which the fetus is a male. These two cases help illustrate the importance of genetic counseling when offering FISH as a testing option and when explaining FISH results. Physician Attitudes on CF Carrier Detection: Incorporating Genetic Testing into Routine Care J. Borsuk, M. Barth, E. Pergament, and B. Fine Northwestern University, Chicago, Illinois 60611 Physician attitude was evaluated in regard to offering couples in the prenatal population the opportunity for carrier detection of cystic fibrosis (CF). Sixty-one obstetricians participating in the study were placed in one of three groups: (1) Those offering carrier detection at the present time; (2) those planning to offer carrier detection in the near future; and (3) those opposing the offering of routine CF carrier detection. Agreement with attitude state-

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ments were compared among the three groups concerning CF carrier detection and (a) the liability incurred if testing not offered; (b) the effects of testing on patients; (c) the logistics of routinely offering testing; (d) its ethical implications; and (e) the medical aspects of carrier detection. All physicians agreed that patients had a right to know their carrier status; that they favored the use of a carrier test with a 100% detection rate, and that consensus statements from professional groups influenced their practice. Nevertheless, all three groups reported that the recent NIH consensus statement on genetic testing for CF would not influence their opinions about offering couples in the prenatal population carrier detection. Physicians opposed to carrier testing were more likely to agree that their patients would have difficulty understanding the nature of CF testing (62% vs. 54% and 37% for groups offering or planning to offer, respectively) and would be falsely reassured by a negative test result (69% vs. 36% and 47% for groups offering or planning to offer, respectively); that routine genetic testing has eugenic implications (54% vs. 8% and 18% for groups offering or planning to offer, respectively); that carrier frequency was not high enough to warrant routine genetic testing (39% vs. 8% and 14% for groups offering or planning to offer, respectively); that offering carrier detection testing for CF to all patients would not be too time consuming (15% vs. 46% and 40% for groups offering or planning to offer, respectively); that they were least confident in their ability to counsel patients about carrier testing for CF (15% vs. 31% and 43% for groups offering and planning to offer, respectively); and, that a deterrent to offering CF carrier testing was the current detection rate of 90% (54% vs. 33% and 24% for groups offering and planning to offer, respectively). If free, only 46% of opposing physicians would routinely offer CF carrier testing vs. 67% and 71% for physicians offering and planning to offer, respectively. Population screening for an increasing number of genetic disorders is anticipated as a consequence of the Human Genome Project. Since physicians are ultimately responsible for dispensing new genetic tests, it is important to assess their attitudes about carrier testing, in order to minimize existing barriers and to ensure patient access. By identifying and then addressing the concerns of physicians, genetic counselors may not only materially assist in the development of genetic testing programs for CF but also begin to define strategies for the successful implementation of genetic testing programs for various other genetic disorders as well. An Exploration of Reproductive Decision-Making and Childbearing Motivations for Individuals with Ehlers-Danlos Syndrome J. Follmer, E. Pergament, and J. Schiffman Northwestern University, Greenwood, Indiana 46143 In addition to possessing the potential to pass on their genetic condition, persons with Ehlers-Danlos syndrome (EDS) confront many reproductive issues including uncertainty of clinical course and pregnancy-related maternal morbidity and mortality. This study was designed to examine these issues, motivations, and concerns which are influential in the reproductive decision-making process for affected individuals. A questionnaire, which was conducted via an international list-serve connecting approximately 200 persons affected with EDS, addressed these and other related genetic counseling issues. Participants also provided personal narratives which were included for qualitative analysis in the study. This novel approach was used in an attempt to access a diverse population that was active and willing to discuss their conditions. Twenty-three women diagnosed with EDS subsequently responded. (Only three men returned questionnaires; therefore, they were eliminated from the analysis.) 5/12(41%) considered EDS when contemplating pregnancy (five had not been diagnosed until after their families had been completed). 6/11(54%) of those without children stated that their decision was a direct result of having EDS. Seventy-one percent reported that earlier diagnosis would have changed their decision to have children. Eighty-two percent of women who experienced pregnancy complications from EDS decided not to have more children. Five(62%) chose increasing self-esteem as their second most influential motivation for reproduction; 3(43%) of those with children chose uncertainty of their future health as their primary concern; seventy-three percent of those women without children chose either the ability to endure

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Clinical Genetics and Screening Issues Abstracts

pregnancy or care for a child as their main concerns. Seventy-four percent indicated that genetic counseling would have been a useful service. Having EDS significantly affected reproductive decision-making in this population. Increasing self-esteem was shown to be a motivating factor for those women considering reproduction. Uncertainty of their future health was the primary reproductive concern of those women with children, while those without children were concerned about their physical ability to endure pregnancy or care for a child. Since a majority of women with EDS expressed that they would benefit from genetic counseling services, genetic counselors must be aware of such contributory factors in the reproductive decision-making of EDS patients. Asking Patients to Assist with Recruiting at Risk Relatives for Gene Testing an Invasion of Privacy? Can They Do It? T. Jennings, M. Dugliss, N. Callanan, B. Cheuvront, I. M. Lubin, J. Sorenson, and G. White

University of North Carolina at Chapel Hill, North Carolina 27599 One means of recruiting high-risk populations into genetic carrier testing research is to ask patients to inform at-risk relatives about the research. Since little data are available on whether patients view this as an invasion of privacy and whether they believe they can contact relatives, data are presented from an ongoing hemophilia A carrier testing study. This study offers free hemophilia education, genetic counseling, and carrier testing to women with at least a 121/2% risk to have a son/grandson with hemophilia A. We have contacted 111 patients (or mothers) followed at a large hemophilia clinic. Twenty were ineligible for, and 11 remain undecided about informing their at-risk relatives of this study. Of the remaining 80, 22 (28%) decided not to, while 58 (73%) decided to inform their relatives. Among patients completing a self-administered questionnaire, 92% said that our asking if they would contact female relatives was not an invasion of privacy. Eighty-eight percent reported they could contact these relatives, 83% reported they had an obligation to inform their at-risk relatives. Less, 60% had previously discussed carrier testing with at-risk relatives. Thus far, 28 (47%) patients have results pending, one (2%) patient is inconclusive, and 29 (50%) had a disease causing or disease associated mutation identified. All patients with identified mutations were (or will be) asked to contact their at-risk relatives. On average each patient needs to contact six relatives (with a range of 1-34 relatives). Currently, 27 patients have been informed of their test results. These patients have yielded 149 eligible relatives. Patients reported 25 (17%) relatives did not want researchers to contact them. Ten (7%) relatives cannot be contacted by the patient or the patient refuses to contact. We are waiting for patients to provide contact information on 64 (43%) relatives. Fifty (34%) relatives have agreed to be contacted by our study. On average, 54.5 days have passed from the time a patient was told their results to our first attempt to contact their relatives (with a range of 0-214 days). Of the 50 relatives, 48 (96%) have been contacted. For these 48, approximately 5.3 days pass from the time research personnel have permission to contact a relative and the relative is contacted. Once this contact is established, it takes on average 9.2 days to have a relative complete the first telephone interview. These early results suggest: (1) while most of our population reported they had an obligation to inform at-risk relatives, fewer had previously discussed such testing with their relatives. (2) although invasion of privacy and inability to contact at-risk relatives may concern IRBs and researchers, most patients are not concerned. As the study continues, we will assess whether participants and nonparticipants differ in their opinions on these issues. (3) Though most patients believe they can contact their at-risk relatives, the time it takes them to contact and give information to us is considerable, with an average time lapse of 8 weeks. During this time, research personnel have used various tools to decrease the time of gathering contact information, such as reminder telephone calls, re-approaching patients in clinic, and writing letters. Once given contact information, it takes researchers approximately 2 weeks to contact and recruit relatives. Therefore, it takes patients almost four times as long to provide contact information, as it takes for researchers to contact and recruit relatives. Thus, researchers and IRBs should consider this added time, when deciding upon acceptable recruitment methods.

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473

Further studies will have to be done to determine if factors such as degree of relationship to the relative or age of patient, have a role in the length of time it takes patients to contact their relatives. Until these studies occur, we will have to identify and develop creative ways that are ethically acceptable, for having patients act as recruiting agents. Normal Outcome of a Pregnancy with a Cystic Hygroma and Trisomy 7 on CVS M. T. Jodah and B. K. Kousseff University of South Florida, Tampa, Florida Confined placental mosaicism (CPM) is identified in approximately 1-2% of pregnancies undergoing Chorionic Villi Sampling (CVS) and refers to the presence of a chromosome abnormality in the sampled placental tissue and not confirmed in the fetus. Depending on the specific chromosome involved, CPM is associated with both normal and adverse pregnancy outcomes, including intrauterine growth retardation (IUGR). We present a normal pregnancy outcome following a diagnosis of cystic hygroma on sonogram and trisomy 7 in CVS sample. At 10.1 weeks, a 24-year old primigravida was referred for suspected nuchal thickening. A repeat sonogram confirmed a cystic hygroma, measuring 4 mm. The couple elected to undergo CVS, which showed 47,XX, +7 in 20 metaphases from cultured mesenchymal cells. Repeat chromosome analysis through early amniocentesis at 13.5 weeks showed 46.XX in 21 metaphases. Amniotic fluid alpha-fetoprotein was within normal limits (0.79 MoM). At the time of amniocentesis, the cystic hygroma measured 3 mm. Uniparental disomy studies using seven markers linked to or within the cystic fibrosis transmembrane regulator (CFTR) gene were negative, demonstrating biparental inheritance of the 7q31-32 regions. The couple was counseled regarding favorable outcome with normal chromosomes on amniocentesis and negative UPD studies if cystic hygroma continues to resolve. They elected to continue the pregnancy. Due to concern regarding hydrops, IUGR or genetic syndromes such as Noonan syndrome and familial pterygium colli, follow-up sonogram and fetal echocardiogram were performed and were normal. Patient delivered at 39 weeks via spontaneous vertex delivery, with vacuum assistance. Birthweight was 3000 grams (25th centile), length was 48.5 cm (50th centile), head circumference was 34.25 cm (50th centile) and Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. The infant is now 5 weeks old, and by parental report, has no abnormalities. Follow-up placental and cord blood studies were not performed. The presence of a cystic hygroma on fetal sonogram has -50% risk to be associated with a chromosome abnormality, especially Turner and Down syndromes. Trisomy 13 and trisomy 18 are sometimes encountered (Johnson et al., 1993). In the absence of a chromosome abnormality, first trimester cystic hygromas are likely to resolve with no physical abnormalities at delivery (Johnson et al, 1993; Trauffer et al., 1994). The cystic hygroma in the reported patient resolved within a few weeks following the amniocentesis. Trisomy 7 is one of the common chromosome abnormalities identified in CVS samples (Kolousek and Vekemans, 1993; Wostenholme, 1996). Prenatal and postnatal growth retardation has been reported in the presence of uniparental disomy for chromosome 7 (Langois et al., 1995). Kalousek et al. (1996) assessed the outcome of 14 pregnancies with CPM for chromosome 7 and it appears that in the absence of a fetal chromosome abnormality or uniparental disomy, CPM for trisomy 7 has a favorable outcome; this is supported by the outcome in this report. The majority of reported trisomy 7 cases, including 13 of 14 cases in Kalousek's study, were ascertained on the basis of advanced maternal age. In a few patients, it was ascertained through an abnormal finding on sonogram, usually IUGR. This patient was ascertained via sonogram showing cystic hygroma instead of IUGR. The hygroma was probably coincidental to the trisomy 7 in the placental tissue. The favorable outcome of this case study supports outcome data on first trimester isolated cystic hygromas and trisomy 7 which is confined to the placenta. Early Intervention and Special Education Personnel's Awareness of Genetic Services S. B. Kramer

Clinical Genetics and Screening Issues Abstracts

474

Beaver College, Glenside, Pennsylvania 19038 Early intervention and special education services are guaranteed by Federal and many state laws for children from birth to age 21 with disabilities. Due to this fact, most children with disabilities come into contact with early intervention and special education providers early in life and throughout. It has been observed that the special education system historically has not used genetic services for their clientele. This lack of referral and usage of services may be linked to a split in research approaches between the medical and special education communities. It may also be due to a simple lack of awareness regarding genetic services and the potential benefits of genetic services to special education and early intervention. This study evaluates the level of awareness of early intervention and special education personnel in the Commonwealth of Pennsylvania with regard to the availability and access of genetic services. Questionnaires were sent out to the 47 early intervention coordinators and 29 intermediate unit directors covering services in all 67 counties in Pennsylvania. The questionnaires were returned with a 64% and 48% response rate, respectively. These professionals are generally aware that genetic services are available, however, they are not likely to refer clients to genetics professionals. Self-reports showed that 60% of these professionals have not made referrals to genetic services. Only 57% of the participants had any kind of training in genetics. Even if genetics training was provided, the ability to apply the information to present situations was lacking. These professionals were asked to indicate appropriate reasons for referral (Table I). Reasons for this lack of utilization and referral are explored. Suggestions to increase referrals and utilization of genetic services by these professionals are given. Direct DNA Analysis of the GCT Expansion Mutation Found in Myotonic Dystrophy: A Laboratory's Experience N. Mclntosh, R. Kornreich, and S. Gersen DIANON Systems, Inc., Stratford, Connecticut 06497 Files from 124 samples received for direct DNA analysis of the GCT expansion mutation within the myotonin protein kinase gene were retrospectively reviewed. Information from these cases was entered into a Microsoft Access database and analyzed using the cross-tabulation function. Ninety-six percent of samples received were bloods (58% of samples came from females, 38% from males) and 4% were prenatal (four amniotic fluid samples and one product of conception). The most common ages at which individuals were tested was 1-5 years of age

Table I. Referral Situations Percentage of respondants who would refer to genetics Situation A child with undiagnosed developmental delay Adopted child born with heart defects and developmental delay Parents of a developmentally delayed child are contemplating pregnancy Child with unusual behavior problems that do not respond to intervention Two siblings are being served with the same disabilities

El coordinators

IU directors

Total

66.70%

25.00%

54.80%

40.00%

41.70%

40.50%

76.70%

75.00%

76.20%

36.70%

33.30%

35.70%

86.70%

58.30%

78.60%

Clinical Genetics and Screening Issues Abstracts

475

(28%) followed by 30-40 years of age (19%). The most common indication for testing was a clinical suspicion of myotonic dystrophy (66%). The number of GCT trinucleotide repeats detected ranged from five to approximately 2300. The modal number of GCT repeats in this series was 12. Forty-five percent of cases showed no expansion, and there were no cases that fell into the "gray zone" (36-50 GCT repeats). Six percent of cases had premutations (51-100 GCT repeats), and 50% of cases showed a full mutation expansion. Of the full mutation expansions, 28% fell into the range of 100-500 GCT repeats, 28% fell into the range of 5001000 GCT repeats, and 44% fell into the range of greater than 1000 GCT repeats. The indication most likely associated with a full mutation result was a clinical suspicion of myotonic dystrophy (50/82 or 61%) followed by having a suspected or know family history of myotonic dystrophy (13/38 or 34%). The majority of cases were referred by geneticists (61%), followed by pediatricians (10%). Genetic counselors were listed as being involved in 60% of cases. Genetic counselors were listed on all of the requisitions coming from obstetricians and on 82% of requisitions coming from geneticists (62/76). Of note is the absence of genetic counselors listed on some requisitions; genetic counselors were listed on only 9% of requisitions coming from pediatricians and 20% of requisitions coming from neurologists. This series of cases suggests that clinicians are accurately diagnosing myotonic dystrophy and using the direct DNA test to confirm their clinical suspicions, that prenatal testing is being requested although it does not make up a large percentage of testing, and that genetic counselors might consider marketing their services to a broader range of physicians who order myotonic dystrophy testing (notably pediatricians and neurologists). Development of a Standardized Family History Questionnaire for Research Purposes E. Melvin, W. Scott, M. Speer, C. Wolpert, and M. Pericak-Vance Duke University Medical Center, Center for Human Genetics. Durham, North Carolina 27710 The pedigree has long been an important and standard tool of genetic counselors and other genetic health professionals for evaluating and counseling a family with a genetic disorder. An accurate account of family history and phenotype is especially important when conducting a genetic linkage study. Therefore, it is imperative that interviewers collect accurate information not only on each individual in a particular family, but also across all research families. However, unstructured family history interviews by different interviewers may obtain different information. Therefore, we have developed a standard approach to eliciting family history information for genetic epidemiology studies. The standardized form, called the "Family History Questionnaire," is designed to capture the general demographic, relationship, and health status information needed for ascertainment of families into genetic linkage studies. Adaptations are made for inclusion of disease-specific questions for both Mendelian and complex disorders. The form was designed with several goals in mind. First, the same data are collected on every individual in each family to increase reliability. Second, we assume that family members provide the most accurate knowledge of medical history on relatives who are the most closely related. Therefore, the informant/historian is limited to the proband or the proband's parents, spouse, or children to ensure the most accurate and complete information on the proband and his or her first-degree relatives. Third, a protocol has been established to collect information on all first-degree relatives of all additional affected family members, no matter how distantly related from the proband. This data not only assists in determining mode of inheritance and/or recurrence risk, but also identifies other branches of the family which should be explored. The initial informant is asked to provide as much information as possible on these distant relatives. However, additional family informants are identified and the standard interview is repeated with these more distant branches for purposes of more accurately extending the pedigree and collecting standard data. Lastly, the standard questionnaire elicits a detailed, three to five generation pedigree (from at least the proband's grandparents to proband's children). This data is collected for purposes of expanding the pedigree in the future or identifying potential participants for longitudinal studies. The "Family History Questionnaire" can help the genetic counselor obtain consistent standard information for the

476

Clinical Genetics and Screening Issues Abstracts

development of a pedigree and may also be adapted for use with standard pedigree-drawing programs or databases. Although the "Family History Questionnaire" was designed for use in the research setting, the form may be adapted for the clinical setting as an initial tool for identifying general conditions running in a family or for targeted disorders. However, as with all family member-reported information, it is still imperative to confirm pertinent diagnoses with the medical record. Current Genetic Screening Practices of IVF Centers that Participate in Oocyte Donation S. M. Morgan, L. West, M. Cedars, and N. S. Warren University of Cincinnati, Cincinnati, Ohio 45229 Oocyte donation using donor gametes is some couples' only option to conceive a pregnancy. It is estimated that there are 2500 cases of oocyte donation annually (Sauer, 1996). The purpose of this study is to determine the current practices of in vitro fertilization (IVF) centers regarding genetic screening of oocyte donors. In 1993, the American society for Reproductive Medicine (ASRM) suggested that IVF centers screen gamete donors for genetic disease, however, their recommendations for screening are vague. According to the ASRM, the donor should be young, not have a major mendelian disorder, should not be heterozygous for an autosomal recessive gene for which carrier testing is available, have no major malformations or familial disease with a major genetic component, and should not carry a chromosomal rearrangement. Yet, IVF centers ar not required to carry out any genetic screening on potential oocyte donors. IVF centers in the United Stats which participate in oocyte donation were surveyed using a questionnaire designed specifically for this study. A total of 190 questionnaires were sent to nurse coordinators in IVF centers that participate in oocyte donation across the United States. Sixteen respondents reported that they no longer participated in oocyte donation. Eighty questionnaires were returned for an overall response rate of 45%. The majority of clinics have participated in oocyte donation between 4-7 years (63.5%). Most centers perform carrier testing for Tay Sachs (78%), a-thalassemia (63.9%), p-thalassemia (63.9%), sickle cell anemia (79.5%), and an Ashkenazi Jewish panel (68.1%) for donors of the appropriate ethnic background. However, about half of all programs do not screen any donors for cystic fibrosis (52.8%). The majority of centers (69.9%) do not karyotype any donor. Those that do karyotype donors usually do so based on recipient request. Most IVF centers do not have a genetics professional on staff (80.8%). IVF physicians address genetic issues that arise with the donors (64.4%). Many centers will refer their patients to a genetics center (61.6%), if necessary. With the continually increased need for oocytes and the shortage of anonymous and known donors, genetic counselors can play an important role in risk assessment of donors and counseling of oocyte donors and recipients. Nurse coordinators believe that they do need to learn more about genetics in general; they feel that this could best be accomplished by workshops focusing on genetics and the acquisition of educational materials to be used in assessing genetic risk factors. Genetic counselors can share the information that they have with the IVF industry by designing educational materials for nurse coordinators to help them identify when genetic tests, counseling, and/or referrals are indicated. Confronting Stigma: Parenting Children with Proteus Syndrome and Related Conditions K. F. Peters and L. Blesecker National Human Genome Research Institute, Bethesda, Maryland 20892 Irregular overgrowth conditions present major educational and counseling challenges for genetic counselors. One such disorder is Proteus syndrome, a hamartoneoplastic condition characterized by gigantism, hemihypertrophy, tumors, exostoses, and accelerated growth, and progressive disfigurement. The purpose of this study was to use a qualitative approach to explore and describe common psychosocial issues for parents of individuals with Proteus syndrome and related conditions. We assessed thirty parents (twenty mothers and ten fathers)

Clinical Genetics and Screening Issues Abstracts

477

of affected individuals, using a semi-structured interview approach. The majority of parents described feeling that they and/or their children have been stigmatized because of the condition. The participants described stigmatizing characteristics of the overgrowth disorder, which are consistent with dimensions of stigma previously reported by Goffman (1963) and Jones (1984). These features include aesthetics, concealability, course, disruptiveness to social interaction, cause, and threat to the affected individual's life. Additionally, three collateral issues for the study group were identified. These include rarity of the disorder, lack of comprehensive information and uncertainty, with the latter as a primary, chronic psychological obstacle. These data suggest that the psychosocial sequelae of parents of individuals with Proteus syndrome and related conditions, with specific attention to issues of stigmatization, should be followed over time. With expertise in education and counseling about unusual and ambiguous diagnoses, genetic counselors are ideally positioned to investigate and address the psychological and social needs of these parents. References Goffman E (1963) Stigma: Notes on the Management of Spoiled Identity. New York: Simon

and Schuster. Jones E et al. (1984) Social Stigma: The Psychology of Marked Relationships. New York: W. H. Freeman and Co. Apparently Balanced Complex Chromosome Rearrangement of Chromosomes 2 and 10 in Two Generations with Variable Phenotype L. A. Rimer, L. L. Estabrooks, and V. Klmonis Southern Illinois University School of Medicine, Springfield, Illinois 62794

We report the clinical and cytogenetic findings of a 17-month-old male and his mother referred for genetic evaluation. The infant presented with developmental delays, dysmorphic facial features, bifid uvula, and third and fourth finger partial syndactyly on the left hand. His mother had a mild learning disability requiring special education in addition to preaxial polydactyly. Chromosome analysis on the proband and his mother revealed a complex chromosomal rearrangement consisting of a paracentric inversion on the long arm of chromosome 2, pericentric inversion of chromosome 10, and reciprocal translocation between the long arm of chromosome 2 and the long arm of chromosome 10 [46XY,der(2,10)inv(2)(q23q31)t(2;10) (q32;q21.2)inv(10)(pll.lq21.1)]. This was confirmed by whole chromosome painting of 2 and 10 and FISH and a 10q22 probe and a 2 centromeric probe that established the breakpoints. Chromosome analysis on the proband's full and maternal half sibling were normal. We hypothesize that a subtle deletion or duplication at these breakpoints not detectable by FISH occurred during the transmission of this complex chromosome rearrangement from mother to son, resulting in varying phenotypes. Since there are six separate breakpoints involved in this rearrangement, genetic counseling regarding risk for abnormal offspring is difficult to estimate. Genetic Counseling for the CF 5T Variant; Experience and Dilemmas S. Roberts, N. Adams, and T. Brown

LabCorp, Research Triangle Park, North Carolina Intron 8 of the cystic fibrosis transmembrane regulator (CFTR) gene contains a thymidine (T) tract with 5, 7, or 9 Is. The 5T allele has been shown to cause skipping of exon 9 in about 50-60% of transcripts, resulting in an abnormal CFTR gene product. When the 5T is found in combination with another CF mutation or in the homozygous state, reported phenotypes range from asymptomatic to congenital bilateral absence of the vas deferens (CBAVD)

478

Clinical Genetics and Screening Issues Abstracts

or bronchiectasis. No controlled prospective studies have been reported to date that can identify the likelihood that a 5T compound heterozygote or homozygote will express a given phenotype. The carrier frequency is thought to be about 5%, but this has not been definitively established for different ethnic groups. This creates multiple counseling dilemmas. In order to assist genetic counselors with some of these concerns, we present here the data from a commercial lab with a screening protocol including analysis for the 5T allele. 740 specimens representing bloods (718) and amniotic fluids (22) were screened for 16 common CFTR mutations, the polymorphisms F508C, 1507V, and I506C, and the 5/7/9 T tract. The indications for analysis included "routine screening" (224), Jewish heritage screening (129), suspected diagnosis of CF (103), positive family history of CF (101), spouse with family history of CF (58), parent of fetus with echogenic bowel (52), fetus with echogenic bowel (20), male infertility (9); no history or indication was available for the remaining 44 patients. Of the 696 patients for whom history was obtainable, 63 (9%) were found to be heterozygous for the 5T The 5T allele was detected in three (20%) of the 15 samples submitted for male infertility, including two deltaF508/5T compound heterozygotes. In the 102 cases with pulmonary symptoms or a clinical suspicion of CF, 12 (12%) were found to have the 5T allele. Two deltaF508/5T and one R117H/5T compound heterozygotes and one 5T homozygote were identified that were asymptomatic. Of 411 samples submitted for screening in the absence of family history or symptoms, 34 (8.27%) 5T heterozygotes were identified. Based on our experience, the incidence of the 5T allele in healthy, asymptomatic individuals is higher than previously reported, and genotype/phenotype predictions are not possible at this time. Anecdotal experience of our counseling colleagues who saw these patients indicates that the lack of information regarding the effects of the 5T allele and the increased carrier frequency in healthy individuals creates patient anxiety and difficulties in counseling. Therefore, we do not support routine analysis for 5T and recommend it be reserved for patients with symptoms suggestive of 5T involvement. Carrier Testing Among the Ashkenazi Jewish Population B. Rosen and L. Stevens Division of Genetics, St. Luke's—Roosevelt Hospital Center, New York, New York 10021 Among the Ashkenazi Jewish population carrier testing is now possible for a number of autosomal recessive disorders, including Tay Sachs disease, Canavan disease, Niemann-Pick disease, Gaucher disease, and CF. The recent transfer of the Human Genome Project to private industry, with its promise of completion in 3 years, will doubtless add to the rapid development of new genetic tests. Yet the speed with which technological advances have been made has not allowed for a clear consensus among genetic counselors and their institutions regarding appropriate circumstances under which to offer carrier tests. As out patient population includes a large number of individuals with Ashkenazi Jewish ancestry, we have felt a need to make decisions regarding carrier testing in the absence of clear guidelines. Because of the lack of consensus among the genetics community, the NIH Consensus Statement regarding cystic fibrosis screening, and requests for "Ashkenazi Screening" from a small number of patients, we have chosen to discuss the availability of all of the tests listed above (with the exception of Gaucher disease), with any couple reporting partial or full Ashkenazi Jewish ancestry. The resulting frequency with which we offer ethnic screening has allowed us to identify several problems. Patients appear to be confused about the necessity of the tests, and often seem overwhelmed by the number of choices available to them. Those patients who do choose to consider testing frequently have difficulty understanding the concept of recessive inheritance and also appear not to understand the concept of detection rates in DNA carrier testing. Educating our patients has been made more difficult by the fact that there are no comprehensive written patient education materials available for the Ashkenazi Jewish Screen. Most of our patients have never heard of Canavan disease or Niemann-Pick, and have expressed an interest in written materials. Some patients have also expressed concern that the growing number of genetic tests available for the Ashkenazi population may lead to stigma-

Clinical Genetics and Screening Issues Abstracts

479

tization and/or discrimination. Finally, most of our patients have managed care health insurance, and are unprepared for the negotiations which inevitably ensue regarding referrals, laboratory restrictions, and reimbursement. Our approach, after assessing the problems we have encountered, has been threefold. First, we have begun to educate our providers to refer prenatal patients as early as possible, so that they have more time to make decisions regarding carrier testing. Second, we are in the process of developing a comprehensive, written patient education brochure. This brochure will include general information about recessive inheritance, DNA testing and detection rates, and will explain why testing is available for diseases common among Ashkenazi Jews. In addition, it will have separate, removable sections pertaining to each individual disease, so that counselors at other centers may choose which information to give to their patients, and so that additional sections may be added to the brochure as new tests become available. Finally, we are in the process of developing a patient questionnaire, to assess patient understanding of carrier testing, efficacy of the brochures, and patient reaction to the availability of these tests. Acquired Methylmalonic Acidemia in a Breastfed Infant: Issues for the Genetic Counselor S. Schrock-Kelley, M. Abbott, E. Jureckl, and S. Packman

University of California-Berkeley, Berkeley, California 94720 Methylmalonci acidemia (MMA) is an autosomal recessive inherited inborn error of metabolism caused by deficient or absent methylmalonyl-CoA mutase activity, or by abnormalities in the biosynthesis of the cofactor S'-deoxyadenosylcobalamin from vitamin B12. Vitamin B12 (cobalamin) deficiency can also lead to MMA. Although cobalamin deficiency is rare in infancy in industrialized countries, it can be caused by inadequate dietary intake resulting from low cobalamin levels in breast milk. Such deficiency could be the result of a strict vegetarian (vegan) diet, anatomic abnormalities of the gastrointestinal tract or undiagnosed pernicious anemia in the mother. We report a 4-month-old exclusively breastfed infant who, after apparent good health, presented with recurrent seizures characterized by stiffness, fisting, cyanosis, unresponsive staring, and apnea. MMA was diagnosed based on the organic acid pattern, and treated with intramuscular hydroxocobalamin. However, unlike MMA due to an inborn error of cobalamin utilization, serum vitamin 812 levels were low in this child. Further evaluations revealed that the patient's mother had pernicious anemia. While the only symptom of pernicious anemia noticed by the mother was fatigue (which she attributed to being a new parent), physical examination showed impaired peripheral sensation and minimal ataxia, and chemical testing documented antibodies to intrinsic factor and parietal cells. The implications of cobalamin deficiency in the mother's breast milk as a cause of her child's acute episode were revealed to and discussed with the parents. The above clinical sequence created a unique circumstance for the genetic counselor. In contrast to a situation involving prenatal drug or alcohol exposure, the mother was doing what she thought was beneficial for her child (breast feeding), only to learn that her efforts led to her child's seizures and longerterm neurologic disability. An 8-year follow-up revealed the patient to be functioning well in school. However, developmental delays in expressive language and fine motor skills were documented. During discussions with both parents at the 8-year follow-up, it was determined that they employed contrasting coping styles and defense mechanisms in the face of both their daughter's acute episode and the residual neurological deficits in childhood. The father felt that he was not in need of outside support whereas the mother relied on friends, family, and parent support groups. The father overtly expressed denial, and was optimistic that his daughter would fully recover from the seizures caused by acquired MMA. In contrast, the mother was guarded and stated that she was "preparing herself for the worst case scenario" (including lifelong intellectual disabilities). Furthermore, the mother began to ideate causes and effects so as to emphasize a reciprocity between herself and her daughter. In such a construction, she helped her daughter recover, while her daughter "saved" her by uncovering the pernicious anemia, which would have resulted in serious neurologic consequences if left untreated. The differences in coping approaches in this couple led to strain in the relationship, similar to

480

Clinical Genetics and Screening Issues Abstracts

that experienced by couples coping with genetic diagnoses or developmental delays in their children. We conclude that: (1) nutritional deficiencies, such as pernicious anemia in a breast feeding mother, must be included in the differential diagnosis of a vitamin-responsive inborn error of metabolism. (2) It is likely that such families will be intensively managed by a medical genetics team, and the genetic counselor of that team will be viewed by the family as an important and ongoing source of counseling, guidance, and support. (3) Many of the issues are the same as those encountered in the counseling of families for a genetic disorder. (4) In view of the above, genetic counselors must be prepared to assist parents in coping with feelings of grief or guilt in this unique situation that is neither genetic nor teratogenic, yet in which a parental condition led to an acute illness and long-term neurological effects in a child. Informing Participants of Research Findings C. Schulz Memorial Sloan-Kettering Cancer Center, New York, New York It is an evolving philosophy that patients who participate in epidemiologic studies are considered partners in research who ar entitled to receive research findings. Although investigators disseminate their findings in scientific publications, they usually do not inform participants of research results directly. Many investigators feel that informing participants of research findings is justified on ethical and moral grounds. However, very little information is available to guide researchers on the best means of providing feedback. Moreover, how this information is perceived by participants and its impact on their behaviors and psychological well-being is largely unknown. In the late 1980s, investigators at New York HospitalCornell and Dana-Farber Cancer Institute in Boston initiated a study in which they sought to quantify the risk of second, primary cancers among a group of 1600 individuals affected with retinoblastoma (RB). The study revealed a substantial risk of second, primary malignancies and a substantial risk of death associated with these cancers, specifically in individuals with bilateral RB who received radiotherapy. The results of this study were published in the Journal of the National Cancer Institute in 1993 (Eng et al., 1993). During the summer of 1995, the investigators sent a letter to 1153 cancer survivors or their parents informing them of the research study results. Eight hundred and fifty-five of these individuals received their medical management from New York Hospital-Cornell and 298 from Dana-Farber. In this study, we will contact by mail and telephone those 855 individuals who were sent the abovementioned letter and were treated at New York Hospital-Cornell to invite them to complete a four-page survey. The survey will ascertain data to assess the emotional reaction to the feedback given, the basic understanding of the information given, and the impact the feedback has had on the participant's health care practices. In addition, the study will survey the participants' recommendations on how research results might best be provided to patients and their family members in the future. We will compare the responses of individuals at high risk of second tumors with individuals at average risk of second tumors. We will also compare the responses of individuals with RB to parents of children with RB, among other variables. Preliminary results from this study indicate that participants would rather receive research findings than not. A majority of respondents found the information to be understandable and useful. On a scale from 1 (not at all) to 5 (extremely) the respondents averaged the following scores in response to the letter's content: sad = 2, anxious = 3, guilty = 1, angry = 2, overwhelmed = 2, and frightened = 3. Most individuals discussed the findings with their physician and a family member. A majority of participants stated that they would prefer receiving a letter describing the research findings with a phone number to call with questions, over that of other alternatives, including receiving the results in person. In conclusion, our preliminary data suggest that participants want to receive research findings. Research protocols should include methods detailing how participants will receive results. Despite the content of the letter, respondents, on average, did not score high on the emotional stress scale. Further studies are needed to determine the risks and benefits of informing participants of research findings. Final results of this study may vary significantly from preliminary data due to an early ascertainment bias.

481

Clinical Genetics and Screening Issues Abstracts Acceptance of Invasive Prenatal Testing in Private Versus Public Health Care Settings M. E. Shaw, C. A. Wicklund, P. Robbins-Furman, and J. P. Crino University of Texas-Houston Medical School, Houston, Texas 77030

Previous investigators have suggested that socioeconomic, racial-ethnic, and other demographic factors may play a role in the use and acceptance of prenatal diagnostic testing. Our objectives were to determine if acceptance of invasive prenatal diagnostic testing (amniocentesis, CVS, or fetal blood sampling) differs between socioeconomic and ethnic groups, and to describe characteristics of patients within these groups which may affect their acceptance of such testing. Our prenatal diagnostic center serves two diverse groups of patients: one referred almost exclusively by private practitioners and another receiving care in the county hospital system. We compared these groups with respect to demographic and referral characteristics and acceptance of invasive testing. Significant differences were seen between the groups in ethnicity, indication for counseling, gestational age at referral, and acceptance of diagnostic testing. These data are summarized in the table below. The differences in acceptance of testing persisted after controlling for ethnicity, indication, and gestational age. By comparison to patients referred by private practitioners, those receiving care in a county hospital system are less likely to choose invasive diagnostic testing following genetic counseling. This difference cannot be solely attributed to the differences observed in ethnicity, indication for referral, and gestational age. Further study is needed to identify other contributing factors.

Private (n = 2577)

County (n = 2468)

p

Ethnicity Black Hispanic White Other

555 495 1201 326

(22%) (19%) (47%) (13%)

404 1726 239 99

(16%) (70%) (10%) (4%)

0.0000035

Abstracts from the Seventeenth Annual Education Conference of the National Society of Genetic Counselors (Denver, Colorado, October 1998).

Abstracts from the Seventeenth Annual Education Conference of the National Society of Genetic Counselors (Denver, Colorado, October 1998). - PDF Download Free
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