CIGARETTE-SMOKING AND RISK OF ACUTE-LEUKEMIA - ASSOCIATIONS WITH MORPHOLOGY AND CYTOGENETIC ABNORMALITIES IN BONE-MARROW

Background: Cigarette smoking may be a risk factor for leukemia. No de tailed biological mechanism has been proposed, but a causal link is ma de plausible by evidence of systemic effects of cigarette smoke and th e presence in cigarette smoke of chemicals that have been associated w ith leukemia risk. Purpose: Our purpose was to investigate the leukemi a risk associated with cigarette smoking in a multicenter case-control study of acute leukemias in adults. Methods: Adults aged 18-79 with n ewly diagnosed leukemia were contacted to participate in this epidemio logic study when they entered a clinical trial to be treated under pro tocols sponsored by Cancer and Leukemia Group B. Smoking histories for 610 patients with acute leukemia and 618 population control subjects were obtained by telephone interviews. We examined bone marrow samples and classified patients by morphology of leukocyte precursor cells ac cording to the French-American-British (FAB) classification system and , for 378 patients, by the presence or absence of specific clonal chro mosome abnormalities. We calculated odds ratios (ORs) for risk of leuk emia associated with smoking cigarettes. ORs were adjusted for age, ra ce, and sex. Results: Smoking was associated with only a modest increa se in risk for leukemia overall (adjusted OR = 1.13; 95% confidence in terval [CI] = 0.89-1.44). However, among participants aged 60 and olde r, smoking was associated with a twofold increase in risk for acute my eloid leukemia (AML) (OR = 1.96; 95% CI = 1.17-3.28) and a threefold i ncrease in risk for acute lymphocytic leukemia (ALL) (OR = 3.40; 95% C I 0.97-11.9). Among older persons, risks increased with amount and dur ation of smoking. Smoking was associated with increased risk for AML c lassified as FAB type M2 at all ages, with ORs of 1.70 (95% CI = 1.00- 2.90) for those younger than 60 and 3,50 (95% CI = 1.53-8.03) for thos e aged 60 and older. Smoking was also associated with ALL type L2 at a ll ages, with ORs of 1.72 (95% CI = 0.90-3.27) for those younger than 60 and 5.34 (95% CI = 1.03-27.6) for those who were older. Smoking was more common among patients with specific chromosome abnormalities in AML [-7 or 7q-, -Y, +13] and in ALL [t(9;22)(q34;q11)]. Conclusions: C igarette smoking is associated with increased risk for leukemia and ma y lead to leukemias of specific morphologic and chromosomal types. The association varies with age. Implication: Examining discrete subtypes of disease may permit more accurate assessment of risk. As standardiz ed morphologic classification and cytogenetic and molecular evaluation of leukemia patients becomes more common, epidemiologic studies that take advantage of these advances will begin to contribute to the ident ification of additional risk factors and mechanisms in acute leukemia.