Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India

Abstract

Background: Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population.

Materials and methods: Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups.

Results: The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P = 0.007 and P = 0.005, respectively) between the control and the case subjects.

Conclusion: This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women.

Keywords: MTHFR; PCR-RFLP; breast cancer; genotype; polymorphism.

Figure 1

Frequency of C667T genotype in breast cancer cases and control individuals.

Figure 2

Polymorphism determination of C667T gene by PCR-RFLP. Notes: Homozygous wild, heterozygous, and homozygous mutant genotypes were identified by the presence and absence of 198 bp, 175 bp, and 23 bp bands, respectively. (A) 100 bp ladder marker (L1), CC (L 2, 3), and TT (L 4 and 5); (B) 100 bp ladder marker (L 1), CC (L 2, 3, 6), and CT (L 4 and 5). Abbreviations: L, lane; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism.