Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population

AIM: To investigate the interactions of the DNA repair gene excision repair cross complementing group 5 (ERCC5) and the metabolic gene glutathione S-transferase pi 1 (GSTP1) and their effects on atrophic gastritis (AG) and gastric cancer (GC) risk. METHODS: Seven ERCC5 single nucleotide polymorphisms (SNPs) (rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassARRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population. RESULTS: Two pairwise combinations (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk (P(interaction) = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility (P(trend) > 0.05). When the modification effect of Helicobacter pylori (H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions (ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status (P(trend) = 0.043). CONCLUSION: There is a multifarious interaction between the DNA repair gene ERCC5 SNPs (rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.