Impact of hMLH1 -93G>A (rs1800734) and hMSH2 1032G>A (rs4987188) Polymorphisms on Colorectal Cancer Susceptibility

Background: This study is the first to investigate the association between colorectal cancer (CRC) risk and the hMLH1 -93G>A and hMSH2 1032G>A polymorphisms of mismatch repair (MMR) genes in the Azerbaijani population. Methods: Peripheral blood samples containing EDTA were collected from the study subjects (134 patients and 137 controls), and genomic DNA was extracted using the non-enzymatic salting-out method. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the results were visualized through agarose gel electrophoresis. Results: Overall, no statistically significant correlation was observed between CRC risk and the hMLH1 -93G>A polymorphism in the heterozygous GA (OR=0.76; 95% CI=0.37–1.54; P=0.446), mutant AA (OR=1.47; 95% CI=0.74–2.95; P=0.270), or the A allele (OR=1.062; 95% CI=0.735–1.534; P=0.748). However, in contrast to the dominant model, a statistically significant association was found between the recessive model and a reduced CRC risk, with an odds ratio of 0.56 (95% CI=0.35–0.91; P=0.018). The hMLH1 -93G>A polymorphism was identified at a significantly higher frequency across the TNM stages, with the distribution showing statistical significance (P0.05). Additionally, no statistically significant association was observed between the hMSH2 1032G>A polymorphism and CRC risk. Conclusions: Our results indicate that the hMLH1 -93G>A polymorphism, particularly under the recessive model, may play a protective role against CRC risk in the Azerbajani population. Further studies are required to validate these results and investigate the underlying biological mechanisms. Keywords: Colorectal Cancer; DNA Repair; PCR-RFLP; hMLH1 -93G>A; hMSH2 1032G>A