Tobacco consumption has interaction effect with protein coding genes to increase esophageal squamous cell Carcinoma risk: A case-control study in Chinese high-incidence region

Background: Esophageal squamous cell carcinoma (ESCC) has reported that smoking was a major risk factor. Genetic predisposition can partially explain the pathogenesis of esophageal cancer in alcohol drinkers. It would also be interesting to investigate the genetic basis underlying the significant disparities in ESCC risk in populations exposed to the same level of smoking. Methods: We recruited 1030 ESCC patients and 1783 healthy individuals in Taixing, China, and selected 101 ESCC-related SNPs for analysis. Logistic regression model was employed with an interaction term for smoking and individual SNPs. The level of smoking was categorized based on pack-years as never smokers, moderate smokers (≤30), and heavy smokers (>30). The relative excess risk of interaction (RERI) and the synergy index (S) were used to evaluate interaction on an additive scale. Genetic risk score was established to quantify gene risk. Results: The SNP HECTD4 rs11066280, CASP8 rs3769823 and ADH1B rs1042026 had an interaction effect with smoking on ESCC risk. Specifically, for rs11066280 T/A, the adjusted OR for moderate and heavy smokers was 1.43 (95% CI = 1.01-2.02) and 1.80 (95% CI = 1.28–2.53), ADH1B rs1042026 showed strong effect in both smoker and alcohol drinkers. GRS indicated that these three SNPs had unsignificant effect in non-smokers and a 2.92-fold risk (95%CI = 1.69-5.11) in smokers.Discussion and Conclusion: In this study, we provide new insights for disease prevention and control of ESCC based on smoking behavior and genetic predisposition.