Association of two ERCC4 tagSNPs with susceptibility to atrophic gastritis and gastric cancer in Chinese

Abstract

Genetic polymorphisms in excision repair cross-complementing group 4 (ERCC4) may contribute to the risk of cancer development. However, there are few reports regarding to susceptibility to gastric cancer (GC) or its precursor, atrophic gastritis (AG). Thereby, we investigated the association between two tag single nucleotide polymorphisms (tagSNPs) rs6498486 and rs254942, which represents the majority of common SNPs of ERCC4 gene, and the risks of GC and AG development in a sex- and age-matched case-control designed study. We found that rs6498486 polymorphism was associated with a reduced AG risk in total population (for AC vs. AA: OR=0.69, 95%CI=0.52-0.94, P=0.016; for AC/CC vs. AA: OR=0.68, 95%CI=0.51-0.92, P=0.010) as well as in the subpopulation of youngers (age<60years) (for AC/CC vs. AA: OR=0.67, 95%CI=0.45-0.99, P=0.048). For the rs254942 polymorphism, compared with the common TT genotype, the genotypes of CT and CT/CC were only observed to reduce AG risk in the subgroups of males (for CT vs. TT: OR=0.64, 95%CI=0.45-0.90, P=0.012; for CT/CC vs. TT: OR=0.66, 95%CI=0.47-0.92, P=0.016) and youngers (for CT vs. TT: OR=0.72, 95%CI=0.53-0.97, P=0.035; for CT/CC vs. TT: OR=0.74, 95%CI=0.55-0.99, P=0.045). However, no significant statistical association of the two SNPs with GC susceptibility was observed in the total population. Only rs6498486 AC and AC/CC genotypes were found to be marginally associated with a reduced GC risk in the subgroup of males (for AC vs. AA: OR=0.69, 95%CI=0.49-0.99, P=0.043; for AC/CC vs. AA: OR=0.71, 95%CI=0.50-0.99, P=0.046). Our findings suggested that the ERCC4 rs6498486 and rs254942 may be associated with AG risk. Further validation of our results in larger populations and additional studies evaluating their molecular function are required.