Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population

Abstract

Background: Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have been associated with risks of many cancers, little is known about their etiology role in gastric cancer (GC) and the potential interacting role with lifestyle factors known to damage DNA.

Methods: A population-based study was conducted in 3 counties (Jintan, Taixing and Huaian) of Jiangsu Province, the high-risk areas of GC in China. We investigated the association of polymorphisms IVS12-6T>C and IVS10+12G>A in MSH2 gene with the risk of GC and the potential gene-lifestyle interaction.

Results: The risk of GC was found to be associated with the IVS12-6C allele (CC vs TT, OR=2.34, 95% CI: 1.17-4.71) and IVS10+12A allele (GA or AA vs GG, OR=1.55, 95% CI: 1.14-2.21; and GA vs GG, OR=1.51, 95% CI: 1.04-2.17). Stratified analysis indicated that an increased risk of GC also was observed in: suspected familial subjects carrying the IVS12-6T>C (OR=1.68, 95% CI: 1.27-2.66) or IVS10+12G>A (OR=2.57, 95% CI: 1.53-4.10); or younger subjects carrying the IVS12-6T>C (OR=2.15, 95% CI: 1.24-3.91) or IVS10+12G>A (OR=2.23, 95% CI: 1.20-4.33); or male subjects carrying the IVS10+12G>A (OR=1.64; 95% CI: 1.10-2.54). Furthermore, the combined IVS12-6CC and IVS10+12AA genotypes also significantly increased the risk of GC (OR=2.12, 95% CI: 1.22-3.66). Statistically significant interactions were observed between: IVS10+12G>A and drinking, high pickled food or fried food intake (OR=2.32; 95% CI: 1.43-3.78, OR=2.55; 95% CI: 1.48-4.21 and OR=2.88; 95% CI: 1.70-4.94, respectively); and IVS12-6T>C and high pickled food intake or fried food intake (OR=2.65; 95% CI: 1.62-4.47 and OR=2.48; 95% CI: 1.42-4.13, respectively).

Conclusion: The IVS10+12G>A and IVS12-6T>C polymorphisms in MSH2 gene appear to be associated with risk of GC in this Chinese population. Risk for GC, stratified by related genotypes, was further modified by drinking, high pickled food or fried food intake. Larger prospective studies are needed to confirm these findings.