| Summary: | 碩士 === 國防醫學院 === 公共衛生學研究所 === 93 === Objectives : It has been known that folate metabolism is associated with DNA synthesis, repair, and methylation. A common 677C→T polymorphism in the gene of methylenetetrahydrofolate reductase(MTHFR)and 2756A→C polymorphism in the gene of methionine synthase(MS), which are the key enzymes in the metabolism of folate, have been associated with changed homocysteine levels and resultant DNA methylation, and then, in turn, could be associated with breast cancer risk. A hospital-based case-control study, including 164 breast cancer cases and 322 cancer-free matched controls, were conducted to evaluate the relationships of concentrations of folate and homocysteine as well as polymorphisms in MTHFR and MS genes with breast cancer risk.
Methods : All subjects completed an in-person interview that used a structured questionnaire. Erythrocyte levels of folate was determined by immunoassay and plasma levels of homocysteine was determined by enzymatic assay. Polymorphisms in MTHFR(C677T) and MS(A2756G) genes were determined by real-time quantitative PCR. Logistic regression models were used to compute odds ratios(ORs) and their 95% confidence intervals (CIs).
Results : There was decreased risk of breast cancer risk associated with MTHFR C677T polymorphism in premenopausal women(OR=0.54, 95% CI=0.31-0.95), whereas, an increased risk of breast cancer in relation to MTHFR C677T polymorphism was found in postmenopausal women (OR=2.23, 95% CI=1.03-4.83). However, there were no significant associations between MS A2756G polymorphism and erythrocyte folate levels with breast cancer risk. More interestingly, a significant association of plasma homocysteine levels and increased breast cancer risk was observed in this study population.
Conclusions : The association of MTHFR C677T polymorphism with breast cancer risk appeared to be modified by menopausal status. Plasma level of homocysteine was a significant independent risk factor for breast cancer in Taiwanese women.
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