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A Prospective Study of the Effect of Alcohol Consumption and ADH3 Genotype on Plasma Steroid Hormone Levels and Breast Cancer Risk¹

Departments of Epidemiology [L. M. H., S. E. H., D. S., G. A. C., W. C. W., D. J. H.], Nutrition [S. A. S-W., W. C. W.], Biostatistics [D. S.], and Cancer Cell Biology, [K. T. K.], Harvard School of Public Health, Boston, Massachusetts; Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts 02115 [S. E. H., K. T. K., G. A. C., W. C. W., D. J. H.]; and Harvard Center for Cancer Prevention, Boston, Massachusetts [G. A. C., D. J. H.]

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.

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