Genetic variants at 1q22 and 10q23 were identified as genetic markers of both gastric cancer and esophageal squamous cell carcinoma susceptibility by two genome-wide association studies. The aim of this study was to determine whether rs4072037A > G in MUC1 at 1q22 and rs2274223A > G in PLCE1 at 10q23 are associated with a risk of gastric cancer in a Korean population. We conducted a large-scale case-control study of 3,245 patients with gastric cancer and 1,700 controls. The allele frequencies of rs4072037G and rs2274223G were 11.2 and 25.5% among patients with gastric cancer, compared with 12.8 and 26.4%, respectively, among controls. We found that the rs4072037 AG genotype was significantly associated with a reduced risk of gastric cancer [odds ratios (OR) = 0.78; 95% confidence interval (CI) = 0.67-0.91 for AG vs AA]. Compared with the rs2274223 AA genotype, we found a significant association between the rs2274223 AG genotype and a weakly reduced risk of gastric cancer (OR = 0.87; 95% CI = 0.76-0.99 for AG vs AA). Our data suggest that genetic variants at 1q22 and 10q23 play a role in gastric carcinogenesis.