IJC International Journal of Cancer
This issue includes a special section on the genetic causes and treatment-related implications of multiple cancers and on the interpretation of key epidemiologic measures, with a part on multiple cancers. The paper by Cezary Cybulski, Safia Nazarali and Steven A Narod “Multiple Primary Cancers as a Guide to Heritability” reviews hereditary cancers which are now known to be caused by any of some 100 predisposition genes. Features indicative of syndromatic cancer include a positive family history, early age of onset and multiple primary cancers in an individual. Multiple cancers may be at the same site (e.g. bilateral breast cancer or multiple melanomas) or at different sites, the specific site combinations often being the consequence of the pleiotropic effects of the same gene. In addition to reviewing some of the main cancer syndromes, the authors address the timely issue of clinical gene testing. They present two possible approaches; one trying to covers all genes that might predispose to a single type of cancer and the other making use of a gene panel for all 100 predisposition genes. In the very near future there will be no technical (or financial) limitations to cover the whole genome but this will shift the emphasis and indications in clinical genetic counseling. Much of the time spent on meticulous pedigree confirmation in pretest counseling currently will then be shifted to posttest interpretation of complex genetic data. Daniel K. Choi, Irene Helenowski and Nobuko Hijiya in their paper “Secondary Malignancies in Pediatric Cancer Survivors: Perspectives and Review of the Literature” review the long term sequelae of successful cancer therapy which is increasingly being recognized to be an issue especially in the context of many pediatric cancers. Indeed while the development of effective therapies over the last fifty years have resulted in many previously fatal cancers now being curable there is long term risk of other cancers and co-morbidity. Notably, all the main therapeutic modalities used in the management of childhood cancer - alkylating agents, topoisomerase inhibitors and ionizing radiation- cause therapy-related cancers. Children are more vulnerable than adults to carcinogenic effects DNA damaging therapies and because of good survival the observation times have been extended to some
C 2014 UICC Int. J. Cancer: 135, 1755 (2014) V
40 years. Choi et al point out that in addition to the increased incidence of therapy-related cancers in pediatric cancer survivors, there remain a significant source of mortality. Key is that the related mortality exceeds that of all other causes 25 years after first cancer diagnosis. This review also discusses heritable causes of childhood cancer and, as pointed out by Cybulski et al., inherited predisposition can often cause cancer at multiple sites. As an important conclusion, Choi et al state “As survivors of pediatric cancers live longer, it will be important for pediatric oncologists to understand the long term risks associated with the development of secondary malignant neoplasms or subsequent primary cancers in their patients.” In the third article “Cancer incidence, survival and mortality: explaining the concepts” Libby Ellis, Laura M Woods, Jacques Este`ve, Sandra Eloranta, Michel P Coleman and Bernard Rachet devote a section to the epidemiologic treatment of multiple cancers. This is a less well developed area of cancer epidemiology, particularly in relationship to survival analysis. The majority of the paper is focused on the interpretation of the measures ‘incidence’, ‘mortality’ and ‘survival’ and the authors illustrate these with examples as to why it is important to consider at least two of these measures in order to make assertions about trends. They emphasize that all three metrics are important in assessing current cancer rates. They may help to understand the complex relative contribution of health promotion initiatives, prevention and screening programs and new therapies which may not influence only cancer rates but co-morbidity and co-mortality.
Kari Hemminki1,2 and Richard S Houlston3 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D69120 Heidelberg, Germany 2 Center for Primary Health Care Research, Lund University, Malm€o, Sweden 3 Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK
Editorial
Special section editorial
This issue includes a special section on the genetic causes and treatment-related implications of multiple cancers and on the interpretation of key epidemiologic measures, with a part on multiple cancers. The paper by Cezary Cybulski, Safia Nazarali and Steven A Narod “Multiple Primary Cancers as a Guide to Heritability” reviews hereditary cancers which are now known to be caused by any of some 100 predisposition genes. Features indicative of syndromatic cancer include a positive family history, early age of onset and multiple primary cancers in an individual. Multiple cancers may be at the same site (e.g. bilateral breast cancer or multiple melanomas) or at different sites, the specific site combinations often being the consequence of the pleiotropic effects of the same gene. In addition to reviewing some of the main cancer syndromes, the authors address the timely issue of clinical gene testing. They present two possible approaches; one trying to covers all genes that might predispose to a single type of cancer and the other making use of a gene panel for all 100 predisposition genes. In the very near future there will be no technical (or financial) limitations to cover the whole genome but this will shift the emphasis and indications in clinical genetic counseling. Much of the time spent on meticulous pedigree confirmation in pretest counseling currently will then be shifted to posttest interpretation of complex genetic data. Daniel K. Choi, Irene Helenowski and Nobuko Hijiya in their paper “Secondary Malignancies in Pediatric Cancer Survivors: Perspectives and Review of the Literature” review the long term sequelae of successful cancer therapy which is increasingly being recognized to be an issue especially in the context of many pediatric cancers. Indeed while the development of effective therapies over the last fifty years have resulted in many previously fatal cancers now being curable there is long term risk of other cancers and co-morbidity. Notably, all the main therapeutic modalities used in the management of childhood cancer - alkylating agents, topoisomerase inhibitors and ionizing radiation- cause therapy-related cancers. Children are more vulnerable than adults to carcinogenic effects DNA damaging therapies and because of good survival the observation times have been extended to some
C 2014 UICC Int. J. Cancer: 135, 1755 (2014) V
40 years. Choi et al point out that in addition to the increased incidence of therapy-related cancers in pediatric cancer survivors, there remain a significant source of mortality. Key is that the related mortality exceeds that of all other causes 25 years after first cancer diagnosis. This review also discusses heritable causes of childhood cancer and, as pointed out by Cybulski et al., inherited predisposition can often cause cancer at multiple sites. As an important conclusion, Choi et al state “As survivors of pediatric cancers live longer, it will be important for pediatric oncologists to understand the long term risks associated with the development of secondary malignant neoplasms or subsequent primary cancers in their patients.” In the third article “Cancer incidence, survival and mortality: explaining the concepts” Libby Ellis, Laura M Woods, Jacques Este`ve, Sandra Eloranta, Michel P Coleman and Bernard Rachet devote a section to the epidemiologic treatment of multiple cancers. This is a less well developed area of cancer epidemiology, particularly in relationship to survival analysis. The majority of the paper is focused on the interpretation of the measures ‘incidence’, ‘mortality’ and ‘survival’ and the authors illustrate these with examples as to why it is important to consider at least two of these measures in order to make assertions about trends. They emphasize that all three metrics are important in assessing current cancer rates. They may help to understand the complex relative contribution of health promotion initiatives, prevention and screening programs and new therapies which may not influence only cancer rates but co-morbidity and co-mortality.
Kari Hemminki1,2 and Richard S Houlston3 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D69120 Heidelberg, Germany 2 Center for Primary Health Care Research, Lund University, Malm€o, Sweden 3 Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK
Editorial
Special section editorial
