Interplay among the Variants of One Carbon Metabolism, Methylenetetrahydrofolate Reductase Polymorphisms and Lung Cancer

Abstract

Introduction: Folates perform an integral task in DNA synthesis, methylationand repair. Methylenetetrahydrofolate Reductase (MTHFR) potrays a key part in the metabolism of folate and regulates the equilibrium between the various forms of folate for DNA synthesis and DNA methylation. MTHFR irrevocably transforms 5,10 methylenetetrahydrofolate to 5-methyltetrahydrofolate, the principal circulating folate and the carbon donor for remethylation processes. MTHFR is vastly polymorphic in the general population. Materials and Methods: It was a case-control study conducted during March 2010 to September 2011 in the Department of Pulmonary Medicine in collaboration with the Department of Biochemistry at Government Medical College and Hospital, Chandigarh, to see whether any association exists between the variants of one carbon metabolism, MTHFR polymorphisms (C677T and A1298C), and lung cancer. Twenty biopsy proven lung cancer patients and 20 age and sex matched cancer-free controls were selected. Results: The mean serum folate in cases was higher (12.84 ng/mL±7.527 ng/mL) as compared to controls (4.46 ng/mL±1.346 ng/mL), suggesting that high levels of serum folate are associated with lung cancer. There was no significant variance in the levels of vitamin B12 and plasma homocysteine between cases and controls. No MTHFR polymorphism C677T was seen in the blood and the bronchial biopsy samples of all cases as well as blood samples of all the controls. The MTHFR polymorphism A1298C was present in the blood as well as bronchial biopsy samples of cases as well as blood of controls. Thus, in the present study, there was no relation of this polymorphism with lung cancer. Conclusion: Polymorphisms in MTHFR may contribute to lung cancer. More research on the basis of cellular and molecular mechanisms of lung cancer is urgently needed to aid in understanding of pathogenesis of the disease.