| Summary: | 博士 === 國防醫學院 === 醫學科學研究所 === 95 === The main purpose of the study is to evaluate relationships of hormonal and anthropometric factors and polymorphisms in genes involved in DNA methylation-associated one-carbon metabolism with breast cancer risk in Taiwanese women. The following study projects were conducted to evaluate the study aim: 1. A prospective study to examine the associations between hormonal and body-size factors in relation to breast cancer risk. 2. A nested case-control study to assess the relationships between polymorphisms in the catechol-O-methyltransferase (COMT) gene, estrogen exposure and breast cancer risk. 3. A nested case-control study to evaluate the associations of the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene, estrogen exposure with breast cancer risk. 4. A hospital-based case-control study to examine the relationships between the MTHFR polymorphisms, plasma folate levels and breast cancer risk, and 5. A hospital-based case-control study to test the association between plasma homocysteine levels and breast cancer risk.
The results showed that there was a significant elevation in breast cancer risk associated with hormonal exposures, as indicated by prolonged duration between age at menarche and age at first birth, and body-size factors of hip circumference. In addition, the polymorphic COMT, a gene that plays a central role in estrogen metabolism, was a susceptible factor for breast cancer, only in the presence of prolonged hormonal exposure. Furthermore, polymorphisms in MTHFR (C677T and A1298C), a key gene residing at a critical metabolic branch point in one-carbon metabolism, were associated with a significant reduction in breast cancer risk. This reduction in risk associated with MTHFR polymorphisms was more pronounced among women with low plasma folate levels. However, an elevated risk of breast cancer predisposed by the MTHFR 677T variant genotype (CT and TT) was observed in women with prolonged exposure to estrogens prior to first full-term pregnancy. More interestingly, the current study results also suggest a possibility that the plasma homocysteine levels could be a metabolic risk factor for breast cancer.
In conclusion, the present study findings provide support for an important role of hormonal exposure and one-carbon metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how genes involved in one-carbon metabolism exert their effect on breast cancer susceptibility.
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