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  • Title: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cancer risk: the Croatian case-control study.
    Author: Reljic A, Simundic AM, Topic E, Nikolac N, Justinic D, Stefanovic M.
    Journal: Clin Biochem; 2007 Sep; 40(13-14):981-5. PubMed ID: 17573062.
    Abstract:
    OBJECTIVES: Methylation abnormalities appear to be important for the pathogenesis of many cancer types. Since methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the methylation process catalyzing reduction of 5,10-methylenetetrahydrofolate to 5-methyl-tetrahydrofolate, C677T polymorphism, which decreases enzyme activity, may be associated with cancer susceptibility. The aim of this work was to investigate the distribution of MTHFR C677T polymorphism between various types of cancer and cancer-free controls and to assess if there is a difference in frequency. MATERIALS AND METHODS: 269 Cancer cases (95 prostate cancer, PC; 81 head and neck, HN; and 93 breast cancers, BC) and 102 healthy controls, free of cancer, were genotyped for C677T MTHFR polymorphism using the PCR-RFLP method. RESULTS: There was no overall difference in C677T genotype distribution between total cancer cohort and controls (p=0.064). However, a significant difference and protective OR was found for the C/T genotype (OR=0.574, 95% CI=0.352-0.935). In a comparison of different cancer types and respective controls, genotype frequencies were significantly different between head and neck carcinoma and controls (p=0.004), again with protective role of C/T genotype (OR=0.356, 95% CI=0.189-0.671). Moderate overrepresentation of C/T was found in respective male controls when compared with prostate cancer patients (p value was 0.074 for C/T vs. C/C comparison). The OR for heterozygous C/T genotype in prostate cancer group was 0.404, pointing to its putative protective role. Genotype and allelic frequencies did not differ significantly between 93 breast cancer patients and their 65 age-matched female controls. CONCLUSION: Our data indicate that the C677T MTHFR polymorphism does not significantly contribute to the inherited genetic susceptibility to breast and prostate cancer, while we show some evidence for possible genetic contribution of this polymorphism to the development of head and neck carcinoma.
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