Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer risk

Objectives: Because alcohol dehydrogenase 3 (ADH(3)) is rate-limiting in alcohol oxidation and is polymorphic, we examined ADH(3) genotype in relation to alcohol intake and breast cancer risk. Methods: We conducted a case-control study among Caucasian women aged 40-85 with incident, pathologically confirmed breast cancer and controls, frequency-matched on age and county. Queries included alcohol intake in the past 20 years. Genomic DNA was genotyped for the exon VIII ADH polymorphism by PCR followed by restriction enzyme digestion. Computation of odds ratios (OR) and 95% confidence intervals (CI) was by unconditional logistic regression. Results: We found increased risk among pre- (OR 2.3, 95%, CI 1.2-4.3) but not postmenopausal women (OR 1.1, 95% CI 0.7-1.7) associated with ADH(3)(1-1) compared to ADH(3)(1-2) and ADH(3)(2-2) genotypes. Risk was increased for premenopausal women with the ADH(3)(1-1) genotype and alcohol intake above the median (OR 3.6, 95% CI 1.5-8.8) compared to lighter drinkers with the ADH(3)(2-2) or ADH(3)(1-2) genotypes. ORs were close to null for premenopausal women in other drinking and genotype groups and for postmenopausal women categorized by genotype and alcohol consumption. Conclusion: Among premenopausal women there may be a group more genetically susceptible to an alcohol consumption effect on breast cancer risk.