Abstract 4618: The risk prediction for esophageal cancer by drinking, smoking, and the polymorphisms of ALDH2 and ADH1B

Background: The impact of drinking and smoking on the risk of esophageal cancer has been established worldwide (IACR, 2012 updated). In our previous study, we found that the polymorphisms ofalcohol dehydrogenases 1B (ADH1B - rs1229984) and aldehyde dehydrogenases 2 (ALDH2 - rs671) were associated with esophageal cancer risk in a Japanese population (Matsuo K, 2001 & Oze I, 2009). However, the extent to which these environmental and genetic risk factors contribute as predictors of esophageal cancer among Japanese is unknown. The objective of our study was to evaluate the performance of a risk assessment model that incorporates both environmental and genetic risk factors in a Japanese population. Methods: We conducted a case-control study with 265 cases and age- and sex- matched 530 controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center (HERPACC). We fit regression models with the risk factors. For discrimination assessment, we compared the area under the curves (AUC) in the receiver - operating curve (ROC) analysis of Environmental model (E-model), Genetic model (G-model), and Inclusive model. In addition, we evaluated contribution to risk prediction for each risk factor by calculating the integrated discrimination improvement (IDI) index. Results: We created a risk prediction model for esophageal cancer by polymorphisms of ADH1B and ALDH2, drinking and smoking. The AUCs were 0.873 (0.847-0.898) for E-model and 0.747 (0.711-0.782) for G-model. The Inclusive model including all risk factors, with an AUC of 0.931 (0.912-0.949), showed promise for stratifying people into different risk groups. We found that each risk factor statistically significantly contributed to risk prediction for esophageal cancer (p< 0.001, the IDI indexes of 0.064 for rs1229984, 0.066 for rs671, 0.220 for drinking and 0.101 for smoking). Conclusion: The risk prediction model that includes these environmental and genetic factors could be useful to classify Japanese into relevant risk groups of esophageal cancer for personalized prevention programs. Citation Format: Hidemi Ito, Isao Oze, Satoyo Hosono, Miki Watanabe, Hideo Tanaka, Keitaro Matsuo. The risk prediction for esophageal cancer by drinking, smoking, and the polymorphisms of ALDH2 and ADH1B. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4618. doi:10.1158/1538-7445.AM2015-4618