A prospective study of the effect of alcohol consumption and ADH3 genotypeon plasma steroid hormone levels and breast cancer risk

One suggested mechanism underlying the positive association between alcohol consumption and breast cancer risk is an influence of alcohol on steroid h ormone levels, A polymorphism in alcohol dehydrogenase type 3 (ADH3) affect s the kinetics of alcohol oxidation and thereby could influence the effect of alcohol consumption on hormone levels. We investigated the ADH3 polymorp hism, alcohol intake, and risk of breast cancer in a nested case-control st udy. Among women in the Nurses' Health Study who gave a blood sample in 198 9-1990, 465 incident breast cancer cases were diagnosed before June 1994 an d were matched to 621 controls. Using conditional logistic regression, we c alculated relative risks and confidence intervals to assess breast cancer r isk for ADH3 genotype, Among postmenopausal controls not using hormones at time of blood collection, partial Pearson correlation coefficients were cal culated to assess the association between alcohol intake and plasma hormone levels according to ADH3 genotype, No association was observed between ADH 3 genotype and overall breast cancer risk (relative risk = 0.9 for slow oxi dizers compared with fast; 95% confidence interval = 0.6-1.3), Among postme nopausal women, ADH3 genotype did not modify the weak association observed between alcohol intake and breast cancer risk (P for interaction = 0.45), S tatistically significant trends in the relationship between alcohol consump tion and hormone level dependent on oxidative capacity (ADH3 genotype) were observed for dehydroepiandrosterone sulfate and sex hormone-binding globul in (P < 0.05), These data suggest that the ADH3 polymorphism modestly influ ences the response of some plasma hormones to alcohol consumption but is no t independently associated with breast cancer risk and does not modify the association between alcohol and breast cancer risk.