The combined sample series presented here, totaling 8,774 UADT cancer cases and 11,982 controls, allowed further exploration of these genetic effects among UADT cancer subsites and strata defined by gender, drinking and smoking. The effects of these three variants were generally present for each UADT sub-sites but more pronounced in esophageal cancers and males (Figure 3). Strong heterogeneity was found with rs1229984 when stratifying by alcohol consumption. Notably, an association was observed in “Ever drinkers-Never smokers”, but not in “Never drinkers-Ever smokers”, suggesting the effect with the rs1229984 variant is mediated through alcohol drinking rather than tobacco smoking. In contrast, the lack of heterogeneity for rs1573496 when stratifying by alcohol use may imply differences in the mechanism of carcinogenesis among these ADH variants.
