Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population

Cervical cancer continues to be the most common cause of death among women in developing countries. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are critical enzymes of folate metabolic pathways. In this work, we have conducted a case-control study to assess the role of these two polymorphisms in cervical cancer development. We obtained blood samples from 200 women with cervical cancer and from equal matched controls and analysed using PCR-RFLP method. We found that the methylenetetrahydrofolate reductase variant CT and CT + TT genotypes decreased cervix cancer risk, statistically significant (OR:0.30, 95% CI: 0.18-0.51, P < 0.001 for CT and OR:0.29, 95% CI: 0.18-0.49, P = 0.0000006 for CT + TT). Similarly in those patients who used oral contraceptive with variant CT genotype, there was statistically highly significant reduced risk of cervix cancer (OR:0.25, 95% CI: -0.12-0.49, P < 0.001) of methylenetetrahydrofolate reductase gene. For the methionine synthase, 2756 variant AG and AG + GG genotypes were similarly associated with highly significant reduced risk of cervix cancer (OR: 0.13, 95% CI: 0.07-0.26, P < 0.001 for AG, and OR: 0.15, 95% CI: 0.08-0.27, P < 0.001 for AG + GG) genotypes. In conclusion, our study suggested that methylenetetrahydrofolate reductase and methionine synthase polymorphisms might have protective effect on the risk of cervical cancer in the North Indian women.