Allelic Variations in 5, 10-Methylenetetrahydrofolate Reductase Gene and Susceptibility to Cervical Cancer in Indian Women

Samar   Husain   Naqvi; Naveen   Kumar   Nandan; Saima      Wajid; Shilpie      Biswas; Sominder   Singh   Juneja; Moshahid      Rizvi; Raminder      Prakash

doi:10.2174/187231208783478498

Abstract

Methylenetetrahydrofolate reductase (MTHFR) gene located on chromosome 1p36.3 catalyses the conversion of 5,10-methylenetetrahydrofolate to 5,methyltetrahydrofolate, the major methyl donor for the conversion of homocysteine to methionine. Two common polymorphisms in the MTHFR gene have been identified, 677C > T in exon 4, leading to substitution of alanine by valine and 1298A > C in exon 7 which leads to the replacement of glutamic acid by alanine resulting into reduced enzyme activity. The potential influence of MTHFR activity on DNA methylation and on the availiblity of uridylates and thymidylates for DNA synthesis and repair makes MTHFR an attractive candidate for cancer predisposing gene. In order to elucidate the role of MTHFR polymorphism in cervical cancer, both the exons for 677C > T and 1298A > C mutations were analyzed among 219 females, including 77 females with normal cervical cytology, 80 with cervical dysplasia and 62 with squamous cell carcinoma of uterine cervix. Females with mutant allele at 677 position (CT/TT genotypes) were found to be almost three times the risk of cervical dysplasia than females with CC genotype [OR, 2.9; (CI, 1.5-5.7)], but were less likely to develop squamous cell carcinoma [OR, 1.5 (CI, 0.7-3.2)]. Similar findings were observed for mutation at 1298 position, females with AC/CC genotypes were almost four times the risk of cervical dysplasia [OR, 4.3 (CI, 2.1-9.0)], as compared to AA genotype. Our study lends further support to the hypothesis that the MTHFR polymorphism (677C > T or 1298A > C) is involved in susceptibility to cervical dysplasia.

Keywords: DNA methylation, MTHFR loci, polymorphism, cervical intraepithelial, Mutation

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