Hines L M, Hankinson S E, Smith-Warner S A, Spiegelman D, Kelsey K T, Colditz G A, Willett W C, Hunter D J
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1099-105.
One suggested mechanism underlying the positive association between alcohol consumption and breast cancer risk is an influence of alcohol on steroid hormone levels. A polymorphism in alcohol dehydrogenase type 3 (ADH3) affects the kinetics of alcohol oxidation and thereby could influence the effect of alcohol consumption on hormone levels. We investigated the ADH3 polymorphism, alcohol intake, and risk of breast cancer in a nested case-control study. Among women in the Nurses' Health Study who gave a blood sample in 1989-1990, 465 incident breast cancer cases were diagnosed before June 1994 and were matched to 621 controls. Using conditional logistic regression, we calculated relative risks and confidence intervals to assess breast cancer risk for ADH3 genotype. Among postmenopausal controls not using hormones at time of blood collection, partial Pearson correlation coefficients were calculated to assess the association between alcohol intake and plasma hormone levels according to ADH3 genotype. No association was observed between ADH3 genotype and overall breast cancer risk (relative risk = 0.9 for slow oxidizers compared with fast; 95% confidence interval = 0.6-1.3). Among postmenopausal women, ADH3 genotype did not modify the weak association observed between alcohol intake and breast cancer risk (P for interaction = 0.45). Statistically significant trends in the relationship between alcohol consumption and hormone level dependent on oxidative capacity (ADH3 genotype) were observed for dehydroepiandrosterone sulfate and sex hormone-binding globulin (P < 0.05). These data suggest that the ADH3 polymorphism modestly influences the response of some plasma hormones to alcohol consumption but is not independently associated with breast cancer risk and does not modify the association between alcohol and breast cancer risk.
饮酒与乳腺癌风险之间正相关的一种潜在机制是酒精对类固醇激素水平的影响。3型乙醇脱氢酶（ADH3）的多态性会影响酒精氧化动力学，从而可能影响饮酒对激素水平的作用。我们在一项巢式病例对照研究中调查了ADH3多态性、酒精摄入量与乳腺癌风险。在1989 - 1990年提供血样的护士健康研究中的女性中，465例新发乳腺癌病例在1994年6月前被诊断出来，并与621名对照进行匹配。使用条件逻辑回归，我们计算了相对风险和置信区间，以评估ADH3基因型的乳腺癌风险。在采血时未使用激素的绝经后对照中，计算了偏皮尔逊相关系数，以根据ADH3基因型评估酒精摄入量与血浆激素水平之间的关联。未观察到ADH3基因型与总体乳腺癌风险之间存在关联（与快速氧化者相比，缓慢氧化者的相对风险 = 0.9；95%置信区间 = 0.6 - 1.3）。在绝经后女性中，ADH3基因型并未改变观察到的酒精摄入量与乳腺癌风险之间的弱关联（交互作用P值 = 0.45）。对于硫酸脱氢表雄酮和性激素结合球蛋白，观察到饮酒与依赖氧化能力（ADH3基因型）的激素水平之间存在统计学显著趋势（P < 0.05）。这些数据表明，ADH3多态性适度影响某些血浆激素对饮酒摄入的反应，但与乳腺癌风险无独立关联，也不改变酒精与乳腺癌风险之间的关联。
