In summary, we observed novel SNP interactions among PGC, PTPN11, and IL1B which modified the risks of gastric cancer and atrophic gastritis and we provided important hints of effect modification by H. pylori infection on the cumulative effect of PGC rs6912200, PGC rs4711690, and PTPN11 rs12229892. Here, PTPN11 is linked to gastric cancer.