Background: As a mismatch repair (MMR) gene, hMLH1 plays an important role in the maintenance of chromosomal integrity. Several studies have investigated the associations of hMLH1 -93G>A (rs1800734) and Ile219Val (rs1799977) in diverse tumor types with discordant results, but their roles in ovarian cancer in the Chinese population remains to be elucidated.
Methods: In a case-control analysis, we assessed the association between these two polymorphisms and ovarian cancer risk in 421 ovarian cancer patients and 689 control subjects in the Chinese population using logistic regression.
Results: We found that the variant hMLH1 genotypes (-93AA and AG) are associated with risk of ovarian cancer (adjusted odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.42-2.89) compared with the -93GG genotype. The A allele increases the risk of ovarian cancer in a dose-dependent manner (P<10-4). Functional test showed that -93A allele increased hMLH1 promoter transcriptional activity and the luciferase activity. However, no significant difference was found in the genotype frequencies at the Ile219Val site between the cases and controls.
Conclusions: These findings indicate that the -93G>A polymorphism in hMLH1 may affect ovarian cancer susceptibility in the Chinese population.