Title of article :
Combined Impact of Polymorphism of Folate Metabolism Genes; Glutamate Carboxypeptidase, Methylene Tetrahydrofolate Reductase and Methionine Synthase Reductase on Breast Cancer Susceptibility in Kashmiri Women
Author/Authors :
Muzaffar Mir, M. Sher-i-Kashmir Institute of Medical Sciences - Department of Clinical Biochemistry, India , Dar, Javid A. Sher-i-Kashmir Institute of Medical Sciences - Department of Clinical Biochemistry, India , Dar, Nazir A. Sher-i-Kashmir Institute of Medical Sciences - Department of Clinical Biochemistry, India , Dar, Nazir A. University of Kashmir - Department of Biochemistry, India , Dar, M. Shafi Sher-i-Kashmir Institute of Medical Sciences - Department of Clinical Biochemistry, India , Salam, Irfana Sher-i-Kashmir Institute of Medical Sciences - Department of Clinical Biochemistry, India , Lone, M. Maqbool Sher-i-Kashmir Institute of Medical Sciences - Department of Radiation Oncology, India , Chowdary, Nissar A. Sher-i-Kashmir Institute of Medical Sciences - Department of General Surgery, India
Abstract :
Background: Folate and methionine play a crucial role in DNA synthesis, repair and the epigenetic profile of cell. Hence, the alterations in the folate metabolism can lead to aberrant proliferation leading to neoplasia. Most of the studies have associated polymorphisms in methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes with reduced risk of cervical and colorectal cancer. However, the association with breast cancer is still controversial. Further, theinvolvement of Glutamate carboxypeptidase II (GCPII) polymorphism in cancer is not known. In the present study, we analyzed if the individual and combined effects of polymorphisms in folate pathway genes viz., MTHFR 677C T, MTHFR 1298A C, MTRR 66A G and GCP II 1561 C T, have any role in altering the susceptibility to breast cancer. Methods: The DNA of 35 female breast cancer patients and 33 healthy individuals, in the Kashmiri population from India, were analyzed using a PCR-RFLP approach for the above mentioned polymorphisms. Results: Individuals carrying the MTHFR 677CT/TT and GCPII 1561 CT genotype showed a 3.5 (95% CI: 3.1-3.7, P 0.02) and 7.7 (95% CI: 6.7-9.1, P 0.001) fold decreased risk for breast cancer than the wild types (MTHFR 677CC and GCPII 1561 CC). Subjects with MTRR 66 G-allele showed a 4.5 fold decreased risk (OR: 0.22, 95% CI: 0.20, 0.24, P 0.0005) compared to the wild type (MTRR 66A). Further, subjects with combined polymorphisms in MTHFR, GCPII and MTRR loci revealed a significant reduction of breast cancer risk. Conclusion: This study indicates (i) a protective role of polymorphisms in MTHFR, GCPII, MTRR against breast cancer inthe study subjects, and (ii) combined effect of polymorphisms is more pronounced than single genetic polymorphism, thereby emphasizing the role of gene-gene interaction in the susceptibility to breast cancer.
Journal title :
International Journal of Health Sciences
Journal title :
International Journal of Health Sciences
