Plasma homocysteine as a metabolic risk factor for breast cancer: findings from a case-control study in Taiwan.

Homocysteine (Hcy) is an intermediary product in methionine metabolism and an elevation in plasma Hcy is a sensitive biomarker for an imbalance in the integrated pathways of one-carbon metabolism. More recently, there has been interest in the potential links between total Hcy, folate and cancer. In this study, the association of plasma Hcy levels with the breast cancer risk was investigated. Questionnaire information and blood samples were taken before treatment from 146 women with newly diagnosed, histologically confirmed breast cancer and 285 age-matched control women who were admitted for health examination. Plasma levels of Hcy and folate were measured by enzyme conversion immunoassay and radioassay, respectively. Dietary intake of B-group vitamins was estimated using a semi-quantitative dietary questionnaire. Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR = 2.89, 95% CI = 1.70-4.92 for the highest tertile as compared with the lowest tertile). Moreover, a similar pattern of enhanced breast cancer risk at higher plasma Hcy levels was observed in both pre-menopausal and post-menopausal women. And this consistent pattern did not differ substantially by level of dietary intake of B-group vitamins. The current study results seem to suggest a possibility that the plasma Hcy levels could be a metabolic risk factor for breast cancer. Future studies are needed to prove causality and provide insight on the mechanism of action of Hcy in breast tumorigenesis.

Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan.

Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both are implicated in carcinogenesis. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate cancer-predisposing factor. To evaluate the C677T and A1298C functional polymorphisms in the MTHFR gene and their associations with breast cancer risk, as well as the potential modifying effect by plasma folate status on the MTHFR-associated risk, a hospital-based case-control study was conducted on a Taiwanese population consisting of 146 histologically confirmed incident breast cancer cases and their 285 age-matched controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping and RIA was used to measure the plasma folate. Statistical evaluations were performed using logistic regression analysis. The plasma folate level was inversely associated with breast cancer risk with an adjusted odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.26-1.05] observed among women who were in the highest plasma folate tertile. The MTHFR 677T and 1298C variant alleles were associated with decreased risk for breast cancer [adjusted ORs were 0.81 (95% CI: 0.54-1.21) and 0.57 (95% CI: 0.36-0.89) for 677CT + TT genotypes and 1298AC + CC genotypes, respectively]. Furthermore, compound heterozygote and homozygote variants (677CT + TT and 1298AC + CC) had greater reduced risk (adjusted OR: 0.11, 95% CI: 0.03-0.43) among women with lower plasma folate levels. These results provide support for the important role of folate metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how MTHFR combined genotypes exert their effect on cancer susceptibility.