Background: The effect of increased alcohol consumption on the risk for gastric cancer (GC) has not been fully elucidated, due to the presence of confounders and gender differences. In this study, aldehyde dehydrogenase 2 (ALDH2) rs671, the genetic polymorphism related to the elimination of acetaldehyde, was used as an instrumental variable (IV) for Mendelian randomization analysis to dissect the role of alcohol in GC risk.

Methods: The study included Korean 450 GC cases and 1,050 controls recruited at the National Cancer Center. Data of 795 GC patients and 4,893 controls from the Korean Centers for Disease Control were used for further validation. The odds ratios (OR) for the ALDH2 genotype and its interaction with alcohol consumption were estimated using multivariate logistic regression. The two-stage control function method was performed using rs671 as the IV for alcohol consumption.

Results: All AG carriers had an OR of 1.26 (95% confidence interval, 1.11-1.42) compared with GG carriers. In a quantitative analysis of alcohol intake, the conventional OR was 1.21(1.09-1.36) and the IV-OR was 0.90(0.63-1.28). Females had low alcohol consumption and did not show a significant risk for GC while males had a high risk for GC.

Conclusions: Alcohol consumption is not associated with a risk for GC by itself, and ALDH2 polymorphism should be considered simultaneously when assessing the risk. Females did not display an evident risk for GC regarding alcohol, partly due to their lower level of alcohol consumption. However, further dissection of gender difference is necessary.

Citation Format: Jeongseon Kim, Sarah Yang, Jeonghee Lee, Il Ju Choi, Young Woo Kim, Keun Won Ryu, Joohon Sung. ALDH2 rs671 polymorphism and alcohol consumption in the risk of gastric cancer: A Mendelian randomization study. [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 800.