Abstract 794: A genetic polymorphism of ALDH2 and breast cancer risk: an analysis of 6,624 cases and 5,750 controls from the Breast Cancer Association Consortium

Abstract

Abstract Background. Numerous epidemiological studies consistently indicate that consumption of alcoholic beverages is an independent risk factor for female breast cancer. Although the mechanism underlying this effect remains unknown, it has been hypothesized that ethanol is mutagenic via its first metabolite, acetaldehyde. An impact of acetaldehyde on the carcinogenesis of several types of cancer has been shown in experimental models and in epidemiological studies in East Asian countries where a functional aldehyde dehydrogenase 2 (ALDH2) polymorphism Glu504Lys (rs671) is prevalent. However, its association with breast cancer risk has not been fully elucidated. We conducted an association analysis of original data from Asian studies participating in the Breast Cancer Association Consortium (BCAC). Patients and Methods. Nine studies were used for this analysis, including 6,624 cases and 5,750 controls. The pooled odds ratio (OR) with 95% confidence interval (CI) for breast cancer risk associated with the ALDH2 polymorphism was estimated using logistic regression models. We estimated unadjusted ORs and adjusted ORs for potential confounders. Results. In the unadjusted (crude) analysis, no significant association between ALDH2 polymorphism and breast cancer was observed, with ORs relative to Glu/Glu, of 1.02 (95% CI = 0.95-1.11; P = 0.51) for Glu/Lys, 1.13 (0.96-1.32; 0.14) for Lys/Lys and 1.04 (0.97-1.12; 0.29) for carriers of any Lys allele. In addition, after adjustment for all potential confounding factors, this lack of significant association was consistently observed, with ORs relative to Glu/Glu, of 0.95 (95% CI = 0.86-1.04; P = 0.25) for Glu/Lys, 0.99 (0.82-1.20; 0.93) for Lys/Lys and 0.95 (0.87-1.04; 0.29) for carriers of any Lys allele. These findings were consistent across ER, PR and HER2 status. Conclusions. No significant association between ALDH2 polymorphism and breast cancer was observed in this study. Considering the established impact of ALDH2 504Lys on the carcinogenesis of several types of alcohol-induced cancer, our findings suggest that acetaldehyde is less influential to the breast carcinogenesis induced by alcohol, as is the case for upper-aerodigestive tract cancers. Citation Format: Tomotaka Ugai, Roger L. Milne, Hidemi Ito, Keitaro Matsuo. A genetic polymorphism of ALDH2 and breast cancer risk: an analysis of 6,624 cases and 5,750 controls from the Breast Cancer Association Consortium. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 794.