We found that rs2274223 was associated with a significantly increased risk of HNC in our population [GG vs. AA: adjusted odds ratio (OR)=1.86, 95% confidence interval (CI)=1.09-3.16; GG vs. (AG/AA): adjusted OR=1.85, 95% CI=1.09-3.12], and the effect appeared to be more prominent among drinkers (P=0.024) and patients with oral cavity cancer (P=0.019).