Promoter polymorphisms in DNA repair gene ERCC5 and susceptibility to gastric cancer in Chinese.

Genetic variations in excision repair cross-complementing group 5 (ERCC5) might influence individual vulnerability to gastric cancer (GC). We investigated effects of two putatively functional polymorphisms in ERCC5 promoter region, rs751402 (+25A>G) and rs2296147 (+202C>T), and their potential interaction with environment factors on the risk of developing GC. We performed a sex- and age-matched case-control design with 400 GC cases and 400 healthy controls for rs751402 and 403 GC cases and 403 healthy controls for rs2296147. Our results showed that rs751402 were associated with increased GC risk (AA vs. GG: OR=1.99, 95%CI: 1.20-3.31, P=0.008; AG+AA vs. GG: OR=1.41, 95%CI: 1.07-1.86, P=0.016), and rs2296147 was also associated with increased cancer risk (CC vs. TT: OR=2.17, 95%CI: 1.04-4.54, P=0.039; CC vs. CT+TT: OR=2.26, 95%CI: 1.09-4.69, P=0.028). In a stratified analysis, rs751402 (AG+AA vs. GG: OR=1.44, 95%CI: 1.02-2.02, P=0.037) and rs2296147 (CC vs. CT+TT: OR=2.33, 95%CI: 1.00-5.44, P=0.050) were also found to be associated with diffuse-type GC risk. The most common GT haplotype (rs751402-rs2296147) showed protective effect for GC development (OR=0.73, 95%CI: 0.58-0.91, P=0.005), and especially for diffuse-type GC (OR=0.68, 95%CI: 0.52-0.90, P=0.006). Genetic effects on increased GC risk seemed to be enhanced by Helicobacter pylori infection, smoking and alcohol drinking, with corresponding adjusted ORs of 4.57, 2.42 and 2.50 for the rs751402 AG/AA variants, and of 5.32, 3.20 and 6.87 for the rs2296147 CC variant, but their interaction effects on GC risk didn't reach statistically significance. ERCC5 rs751402 and rs2296147 polymorphisms might alter the risk of developing GC and especially the diffuse subtype. Further validation of our results in larger populations and additional studies evaluating their function impact are required.