The contribution of benzene to smoking-induced leukemia

Cigarette smoking is associated with an increased risk of leukemia; benzene , an established leuke-mogen, is present in cigarette smoke. By combining e pidemiologic data on the health effects of smoking with risk assessment tec hniques for low-dose extrapolation, we assessed the proportion of smoking-i nduced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts to estimate the leukemogenic potency of benzene. Using multiple-decrement life tables, we calculated li fetime risks of total leukemia and AML deaths for never, light, and heavy s mokers. We repeated these calculations, removing the effect of benzene in c igarettes based on the estimated potencies. From these life tables we deter mined smoking-attributable risks and benzene-attributable risks. The ratio of the latter to the former constitutes the proportion of smoking-induced c ases attributable to benzene. Based on linear potency models, the benzene i n cigarette smoke contributed from 8 to 48% of smoking-induced total leukem ia deaths [95% upper confidence limit (UCL), 20-66%], and from 12 to 58% of smoking-induced AML deaths (95% UCL, 19-121%). The inclusion of a quadrati c term yielded results that were comparable; however, potency models with o nly quadratic terms resulted in much lower attributable fractions-all < 1%. Thus, benzene is estimated to be responsible for approximately one-tenth t o one-half of smoking-induced total leukemia mortality and up to three-fift hs of smoking-related AML mortality. In contrast to theoretical arguments t hat linear models substantially overestimate low-dose risk, linear extrapol ations from empirical data over a dose range of 10- to 100-fold resulted in plausible predictions.