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. © 2010 American Cancer Society.