The association between the ADH variants, rs1573496, rs1229984 and rs698 at 4q23 and UADT cancer was described previously [14] in the CE, ARCAGE (excluding Bremen) and SA studies. When excluding these studies, the association with these variants was independently replicated in the additional 5,092 UADT cancer cases and 6,794 controls presented here (p = 5×10−8, 7×10−9 and 0.02 for rs1573496, rs1229984 and rs698, respectively) (Table 1). We combined all studies totaling 8,744 UADT cancer cases and 11,982 study specific controls to investigate effects of the ADH variants among different strata (Figure 3). For both the ADH1B and ADH7 variants heterogeneity was noted by UADT cancer subsite (p heterogeneity = 0.002, and 0.06 respectively). The rs1229984 ADH1B variant showed strong heterogeneity when stratifying by alcohol, with little evidence for association in never drinkers. By contrast, there was little evidence for heterogeneity noted with rs1573496 and rs698, but a statistically significant association with the ADH7 variant rs1573496 was observed never drinkers (p = 0.03).
