Association of alcohol dehydrogenase polymorphisms and life-style factors with excessive alcohol intake within the Spanish population (EPIC-Spain)

To analyse associations between alcohol dehydrogenase (ADH) polymorphisms and alcohol intake in Spanish men and women.We analysed the relationship between 21 genetic variants in ADH genes and excessive alcohol intake in both men and women. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array and a sex-stratified analysis was performed.Ethanol intake was calculated using a validated dietary history questionnaire.Heavy consumers of alcohol (≥70 g/day in men, ≥42 g/day in women) (653 cases) and very low or non-consumers (2 g/day) (880 controls) from the Spanish cohort of the European Prospective Investigation into Cancer (EPIC).We found statistically significant associations between alcohol intake and known life-style factors; namely, smoking and food energy intake (meat and fruit/seeds) in both men and women, as well as with physical activity in women and educational level in men. Additionally, we found that a non-synonymous coding SNP in ADH1B (rs1229984) is associated inversely with excessive alcohol intake in men [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.11-0.33; P = 4.77E(-10) ) and women (OR = 0.48, 95% CI = 0.27-0.83; P = 0.0067). Furthermore, ADH6 rs3857224 was found associated with heavy alcohol intake in women (OR = 1.61, 95% CI = 1.21-2.14; P = 1.01E(-3) ), but not in men.In the Spanish population, the single nucleotide polymorphism of alcohol dehydrogenase ADH1B, rs1229984, is associated inversely with alcohol intake in both men and women. Another polymorphism of ADH6, rs3857224, is associated with heavy alcohol intake in women.