(19) SCHOENLEIN PV, SHEN D-W, JOHNSON BP, ET AL: The amplification of the
human MDR1 gene occurs via episome formation in KB carcinoma cells. ProcAACR 31:356, 1990 (20) WAHL GM: The importance of circular DNA in mammaUan gene amplification. Cancer Res 49:1333-1340, 1989 (27) SEN S, HITTELMAN WN, TEETER LD, ET AL: Model for the formation of
double minutes from prematurely condensed chromosomes of replicating
Clark W. Heath, Jr* Until 1986, it was largely accepted that tobacco use was not a significant etiologic factor for malignancies of hematopoietic tissues. This belief was held despite evidence in several epidemiologic studies that leukemia rates were about 50% higher in cigarette smokers than in nonsmokers (1). However, no clear dose-response patterns were seen in those studies, and not all of the studies suggested increased risk (2). When relativeriskwas increased, values were generally under 2.0, a range in which confusion with noncausal associations is common. Morerecently,the question of association between tobacco use and hematopoietic malignancies has received closer scrutiny. In particular, updated analyses of data from a large prospective study of US military veterans have shown a pattern of increasing risk with an increase in the number of cigarettes smoked and have suggested an association with the occurrence of myeloid leukemias (3,4). Increased risk was also seen in both of the American Cancer Society prospective studies (5). Relativeriskvalues in those studies seemed greater for myeloid leukemias than for other forms of leukemia in men but not in women; no dose-response patterns were observed. Three case-control studies have also been reported, two suggesting increased risk for nonrymphocytic leukemias (6,7) but one with strongly negative results despite large size and careful execution (8). To this growing epidemiologic experience, Mills and colleagues (9) now add, in this issue of the Journal, a prospective study of leukemia and multiple myeloma risks among 34,000 Seventh-day Adventists, some of whom previously smoked cigarettes. In this population, leukemia risk was doubled and myeloma risk tripled among former smokers. In each instance, risk showed a dose-response pattern, and, among leukemias, the risk seemed highest for myeloid forms. The possible link between cigarette smoking and myeloma incidence, although provocative, has not been closely examined before and, hence, will require further study in other data sets. Observations in previous studies had not suggested any causal relationship. 1800
(22) VOGELSTEIN B, PARDOLL DM, COFFEY DS: Supercoiled loops and
eucaryotic DNA replication. Cell 22:79-85, 1980 (25) HUNT JD, VALENTINE M, TEREBA A: Excision ofN-myc from chromosome
2 in human neuroblastoma cdls containing amplified N-myc sequences. Mol Cell Biol 10:823-829, 1990
Thefindingsof this study with respect to leukemia, however, obviously strengthen the gathering impression that cigarette smoking isrelatedto leukemia risk and that the association is likely to be causal. This concept is supported by the appearance now, in several studies, of dose-responserelationships,as well as the repeated observation that the risk for myeloid leukemia is greater than for lymphoid leukemia. In conflict are the absence of increased risk in some studies, possible inconsistencies in risk between men and women (5), and the fact that almost all values forrelativeriskare in a low range, which often gives epidemiologists concern about spurious causes for observed associations. While such concern is partly dispelled by repeated observations of positive dose-response patterns, it still persists, in view of various disparities in other epidemiologic results. Looking beyond epidemiologic studies for corroborative evidence that a causative link between cigarette smoking and leukemia may exist, one is drawn to the observation that cigarette smoke does contain benzene (among other oncogenic chemicals) and is a source of ionizing radiation (polonium 210). Both benzene and ionizing radiation are known causes of human leukemia. Both, in fact, are particularly associated with nonlymphocytic or myeloid forms of leukemia and have little, if any, effect on frequency of chronic lymphocytic leukemia, the common form of adult lymphoid leukemia. Additional data suggest that exposure to ionizing radiation may heighten risk for multiple myeloma. However, these suggestions of biologic plausibility from other sources of information should not be overemphasized. For both benzene and ionizing radiation, actual dose levels in cigarette smoke are substantially lower than the levels that have been associated with increased risk in other settings. If the etiologic link between cigarette smoking and leukemia is in fact real, thefindingis of considerable importance and so deserves continued research emphasis. Although leukemia is relatively uncommon, cigarette smoking is not. Therefore, in the populations thus far studied, the proportion of total leukemia risk that might be attributed to cigarette smoking (population attributable risk percent) has been estimated in the range of 20% to 30%. The causes of leukemia are largely unknown, and those causes that have been defined (benzene and ionizing radiation) do not appear by themselves to
Received October 25, 1990; accepted October 29, 1990. 'Correspondence to: Clark W. Heath, Jr, MD, Department of Epidemiology and Statistics, American Cancer Society, 1599 Clifton Rd, NE, Atlanta, GA 30329.
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at North Dakota State University on June 4, 2015
Cigarette Smoking and Hematopoietic Cancer
micronudei in drug-treated Chinese hamster ovary cells undergoing DNA amplification. Cancer Res 49:6731-6737, 1989
account for more than a small proportion of all cases. In that setting, cigarette smoking would assume a dominant etiologic role in malignancies of hematopoietic tissue and would, therefore, become a critical target for urgent preventive action, as it has already for so many other cancer sites.
References
(J) KINLEN LJ, ROGOT E: Leukemia and smoking habits among United States veterans. BMJ 297:657-659, 1988 (4) MCLAUGHUN JK, HRUBEC Z, LINET MS, ET AL: Letter Cigarette smoking
and leukemia. J Natl Cancer Inst 81:1262-1263, 1989 (5) GARFTNKEL L, BOFFETTA P: Association between smoking and leukemia in two American Cancer Society prospective studies. Cancer 65:2356-2360,1990 (6) SEVERSON RK: Cigarette smoking and leukemia. Cancer 60:141-144, 1987 (7) BROWNSON RC: Letter Cigarette smoking and risk of leukemia. J Clin Epidemiol 42:1025-1028, 1989 (8) KABAT G C AUGUSTINE A, HEBERT JR: Smoking and adult leukemia: A
(/) AUSTIN H, COLE P: Cigarette smoking and leukemia. J Chronic Dis 39:417^121, 1986 (2) DOLL R, PETO R: Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J 2:1525-1536, 1976
case-control study. J Clin Epidemid 41:907-914, 1988 (9) MILLS PK, NEWELL GR, BEESON WL, ET AL: History of cigarette smoking
and risk of leukemia and myeloma: Results from the Adventist Health Study. J Natl Cancer Inst 82:1832-1836, 1990
Surveys show that people have the greatest confidence in one source of health information—the professionals. That puts you in a unique position of influence among your smoking patients, 90 percent of whom, want to quit. But smokers need more than your recommendation that they should quit. They need your advice on howtoquit—and how to quit for good. To help you tell them how, the National Cancer Institute developed the "Quit for Good" kit. We updated, revised, and streamlined our stop-smoking kits based on the experience of physicians and dentists who tested the kits and used them widely across the country. Now "Quit for Good" is ready for you. The new kit includes a guide f a professionals, booklets for your patients with tips on how to
FOR become and how to stay a nonsmoker, and waiting room materials to introduce the subject. Each kit contains enough materials for 50 patients, To order your free kit, fill out the coupon and mail it today. Help your patients make nonsmoking a new, good habit. Please send me my free "Quit for Good" kit today. Name
Specialty
SOs
Oty
ZIP
Mail to: QUIT FOR GOOD KIT Office of Cancer Cemmurications National Cancer Institute fcASng 31, Boom 10A18 Betwsda, MD 20205
Vol. 82, No. 23, December 5, 1990
EDITORIALS 1801
Downloaded from http://jnci.oxfordjournals.org/ at North Dakota State University on June 4, 2015
HELP YOUR PATIENTS CRUSH THEIR HABIT.
human MDR1 gene occurs via episome formation in KB carcinoma cells. ProcAACR 31:356, 1990 (20) WAHL GM: The importance of circular DNA in mammaUan gene amplification. Cancer Res 49:1333-1340, 1989 (27) SEN S, HITTELMAN WN, TEETER LD, ET AL: Model for the formation of
double minutes from prematurely condensed chromosomes of replicating
Clark W. Heath, Jr* Until 1986, it was largely accepted that tobacco use was not a significant etiologic factor for malignancies of hematopoietic tissues. This belief was held despite evidence in several epidemiologic studies that leukemia rates were about 50% higher in cigarette smokers than in nonsmokers (1). However, no clear dose-response patterns were seen in those studies, and not all of the studies suggested increased risk (2). When relativeriskwas increased, values were generally under 2.0, a range in which confusion with noncausal associations is common. Morerecently,the question of association between tobacco use and hematopoietic malignancies has received closer scrutiny. In particular, updated analyses of data from a large prospective study of US military veterans have shown a pattern of increasing risk with an increase in the number of cigarettes smoked and have suggested an association with the occurrence of myeloid leukemias (3,4). Increased risk was also seen in both of the American Cancer Society prospective studies (5). Relativeriskvalues in those studies seemed greater for myeloid leukemias than for other forms of leukemia in men but not in women; no dose-response patterns were observed. Three case-control studies have also been reported, two suggesting increased risk for nonrymphocytic leukemias (6,7) but one with strongly negative results despite large size and careful execution (8). To this growing epidemiologic experience, Mills and colleagues (9) now add, in this issue of the Journal, a prospective study of leukemia and multiple myeloma risks among 34,000 Seventh-day Adventists, some of whom previously smoked cigarettes. In this population, leukemia risk was doubled and myeloma risk tripled among former smokers. In each instance, risk showed a dose-response pattern, and, among leukemias, the risk seemed highest for myeloid forms. The possible link between cigarette smoking and myeloma incidence, although provocative, has not been closely examined before and, hence, will require further study in other data sets. Observations in previous studies had not suggested any causal relationship. 1800
(22) VOGELSTEIN B, PARDOLL DM, COFFEY DS: Supercoiled loops and
eucaryotic DNA replication. Cell 22:79-85, 1980 (25) HUNT JD, VALENTINE M, TEREBA A: Excision ofN-myc from chromosome
2 in human neuroblastoma cdls containing amplified N-myc sequences. Mol Cell Biol 10:823-829, 1990
Thefindingsof this study with respect to leukemia, however, obviously strengthen the gathering impression that cigarette smoking isrelatedto leukemia risk and that the association is likely to be causal. This concept is supported by the appearance now, in several studies, of dose-responserelationships,as well as the repeated observation that the risk for myeloid leukemia is greater than for lymphoid leukemia. In conflict are the absence of increased risk in some studies, possible inconsistencies in risk between men and women (5), and the fact that almost all values forrelativeriskare in a low range, which often gives epidemiologists concern about spurious causes for observed associations. While such concern is partly dispelled by repeated observations of positive dose-response patterns, it still persists, in view of various disparities in other epidemiologic results. Looking beyond epidemiologic studies for corroborative evidence that a causative link between cigarette smoking and leukemia may exist, one is drawn to the observation that cigarette smoke does contain benzene (among other oncogenic chemicals) and is a source of ionizing radiation (polonium 210). Both benzene and ionizing radiation are known causes of human leukemia. Both, in fact, are particularly associated with nonlymphocytic or myeloid forms of leukemia and have little, if any, effect on frequency of chronic lymphocytic leukemia, the common form of adult lymphoid leukemia. Additional data suggest that exposure to ionizing radiation may heighten risk for multiple myeloma. However, these suggestions of biologic plausibility from other sources of information should not be overemphasized. For both benzene and ionizing radiation, actual dose levels in cigarette smoke are substantially lower than the levels that have been associated with increased risk in other settings. If the etiologic link between cigarette smoking and leukemia is in fact real, thefindingis of considerable importance and so deserves continued research emphasis. Although leukemia is relatively uncommon, cigarette smoking is not. Therefore, in the populations thus far studied, the proportion of total leukemia risk that might be attributed to cigarette smoking (population attributable risk percent) has been estimated in the range of 20% to 30%. The causes of leukemia are largely unknown, and those causes that have been defined (benzene and ionizing radiation) do not appear by themselves to
Received October 25, 1990; accepted October 29, 1990. 'Correspondence to: Clark W. Heath, Jr, MD, Department of Epidemiology and Statistics, American Cancer Society, 1599 Clifton Rd, NE, Atlanta, GA 30329.
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at North Dakota State University on June 4, 2015
Cigarette Smoking and Hematopoietic Cancer
micronudei in drug-treated Chinese hamster ovary cells undergoing DNA amplification. Cancer Res 49:6731-6737, 1989
account for more than a small proportion of all cases. In that setting, cigarette smoking would assume a dominant etiologic role in malignancies of hematopoietic tissue and would, therefore, become a critical target for urgent preventive action, as it has already for so many other cancer sites.
References
(J) KINLEN LJ, ROGOT E: Leukemia and smoking habits among United States veterans. BMJ 297:657-659, 1988 (4) MCLAUGHUN JK, HRUBEC Z, LINET MS, ET AL: Letter Cigarette smoking
and leukemia. J Natl Cancer Inst 81:1262-1263, 1989 (5) GARFTNKEL L, BOFFETTA P: Association between smoking and leukemia in two American Cancer Society prospective studies. Cancer 65:2356-2360,1990 (6) SEVERSON RK: Cigarette smoking and leukemia. Cancer 60:141-144, 1987 (7) BROWNSON RC: Letter Cigarette smoking and risk of leukemia. J Clin Epidemiol 42:1025-1028, 1989 (8) KABAT G C AUGUSTINE A, HEBERT JR: Smoking and adult leukemia: A
(/) AUSTIN H, COLE P: Cigarette smoking and leukemia. J Chronic Dis 39:417^121, 1986 (2) DOLL R, PETO R: Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J 2:1525-1536, 1976
case-control study. J Clin Epidemid 41:907-914, 1988 (9) MILLS PK, NEWELL GR, BEESON WL, ET AL: History of cigarette smoking
and risk of leukemia and myeloma: Results from the Adventist Health Study. J Natl Cancer Inst 82:1832-1836, 1990
Surveys show that people have the greatest confidence in one source of health information—the professionals. That puts you in a unique position of influence among your smoking patients, 90 percent of whom, want to quit. But smokers need more than your recommendation that they should quit. They need your advice on howtoquit—and how to quit for good. To help you tell them how, the National Cancer Institute developed the "Quit for Good" kit. We updated, revised, and streamlined our stop-smoking kits based on the experience of physicians and dentists who tested the kits and used them widely across the country. Now "Quit for Good" is ready for you. The new kit includes a guide f a professionals, booklets for your patients with tips on how to
FOR become and how to stay a nonsmoker, and waiting room materials to introduce the subject. Each kit contains enough materials for 50 patients, To order your free kit, fill out the coupon and mail it today. Help your patients make nonsmoking a new, good habit. Please send me my free "Quit for Good" kit today. Name
Specialty
SOs
Oty
ZIP
Mail to: QUIT FOR GOOD KIT Office of Cancer Cemmurications National Cancer Institute fcASng 31, Boom 10A18 Betwsda, MD 20205
Vol. 82, No. 23, December 5, 1990
EDITORIALS 1801
Downloaded from http://jnci.oxfordjournals.org/ at North Dakota State University on June 4, 2015
HELP YOUR PATIENTS CRUSH THEIR HABIT.
