When we considered the host genetic effects alone, gene–gene interactions consistently contributed to reduced risks of gastric cancer and/or atrophic gastritis, including two-way interactions: PGC rs6912200-PTPN11 rs12229892, PGC rs4711690-IL1B rs1143623 and PTPN11 rs12229892-IL1B rs1143623 and a three-way interaction: PGC rs4711690- PGC rs6912200-PTPN11 rs12229892. The gene discussed is PTPN11; the disease is gastric cancer.