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 al cohol 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, freque ncy-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 P CR followed by restriction enzyme digestion. Computation of odds ratios (OR ) and 95% confidence intervals (CI) was by unconditional logistic regressio n. Results: We found increased risk among pre- (OR 2.3, 95%, CI 1.2-4.3) but n ot 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 premenopau sal women in other drinking and genotype groups and for postmenopausal wome n 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.