Polymorphisms in ERCC2, MSH2, and OGG1 DNA Repair Genes and Gallbladder Cancer Risk in a Population of Northern India

BACKGROUND: Genetic variants of DNA repair enzymes may lead to genetic instability and contribute to gallbladder (GB) carcinogenesis. METHODS: A case-control study (230 GB carcinogenesis patients and 230 controls) was undertaken to evaluate whether genetic variations in 3 DNA repair genes ERCC2 (Asp312Asn [rs1799793] and Lys751Gln [rs13181]), MSH2 (-118T>C [rs2303425] and IVS1+9G>C [rs2303426]), and OGG1 (Ser326Cys [rs1052133] and 748-15C>G [rs2072668]) are associated with GB carcinogenesis risk in a North Indian population. RESULTS: The authors found that the ERCC2 Asp312Asn AA, MSH2 IVS1+9G>C CC, OGG1 Ser326Cys GG and CG+GG, and OGG1 748-15C>G GG and CG+GG genotypes were significantly associated with an increased risk of GB carcinogenesis (odds ratio [OR], 2.1, 1.8, 2.5, 1.8, 2.0, and 1.6, respectively). In contrast, ERCC2 Lys751Gln, and MSH2 -118T>C markers showed no significant associations with GB carcinogenesis risk, although because of the small sample size their effects cannot be ruled out. Female GB carcinogenesis patients with the OGG1 748-15C>G GG, OGG1 Ser326Cys GG, and ERCC2 Asp312Asn genotypes had a greater risk for developing the disease (OR, 3.6, 7.7, and 2.7, respectively). There was a significant interaction between MSH2 IVS1+9G>C and OGG1 748-15C>G polymorphisms (P=.001). Furthermore, individuals with >6 variant alleles of the studied polymorphisms were at 4-fold increased risk for developing GB carcinogenesis. Classification and Regression Tree analysis revealed potential higher-order gene-gene interactions and categorized a few higher-risk subgroups for GB carcinogenesis. CONCLUSIONS: These results suggest that genetic variants in the DNA repair pathways may be involved in GB carcinogenesis etiology. Cancer 2010;116:3160-9. (C) 2010 American Cancer Society.