Alcohol consumption is a recognized modifiable risk factor for breast cancer, and thus of particular interest from a public health perspective. Plausible biological mechanisms for the association between alcohol and breast cancer include altered hormone levels and exposure to acetaldehyde, a pathogenic metabolite of ethanol. However, drinking behaviour as well as susceptibility to alcohol-induced carcinogenesis varies between individuals. A genetic polymorphism in the alcohol dehydrogenase 1B (ADH1B) gene, which has shown a strongly increased oxidation capability for ethanol in vitro, was therefore investigated as a potential modifier of breast cancer risk associated with alcohol consumption. In a population-based case-control study of breast cancer by age 50 in Germany, we investigated the G47A single nucleotide polymorphism in exon 3 of the ADH1B gene among 613 cases and 1128 controls, using a Taqman PCR method. To quantify the risk of individuals who had at least one variant allele compared to subjects who were homozygous for the wild-type allele, we computed odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression. No overall association between ADH1B genotype and breast cancer risk was apparent (OR 1.0, 95% CI 0.7-1.4). However, alcohol consumption was found to differ significantly by ADH1B genotype (p=0.01 among controls). The stratified analysis revealed a significant decreasing trend in breast cancer risk with increasing alcohol consumption for carriers of the ADH1B variant allele, whereas among homozygous carriers of the wild-type allele breast cancer risk increased with increasing amounts of alcohol (OR for ≥ 12g alcohol/day being 0.3, 95% CI 0.1-1.0 and 1.1, 95% CI 0.8-1.6, respectively). However, the gene-environment interaction was not statistically significant (p=0.2). Due to the low allele frequency of the ADH1B variant allele in Caucasians, we were not able to further investigate the group of heavy drinkers from which this difference appeared primarily to arise. Our data therefore suggest that ADH1B genotype is not independently associated with breast cancer risk but may be a weak modifier of breast cancer risk associated with high levels of alcohol consumption.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]