One-Carbon Metabolism and Breast Cancer Survival in a Population-Based Study

摘要

The 5-year survival rate for BC among US women has increased from 75% during 1974-76 to 85% during 1989-95. Despite such marked improvement BC is still the leading cause of cancer mortality among women 20 - 59 years of age and the second leading cause of cancer mortality among all women. Disease-free survival after BC treatment is likely predicted by both tumor characteristics and host factors. The clinical and pathologic parameters that have been shown to influence disease prognosis include tumor size nodal involvement tumor state grade and hormone receptor status and mitotic index expression of multi-drug resistance proteins p53 status and HER's-2/neu status. Meanwhile only a few host factors have been identified that impact disease-free or overall survival particularly those that a patient may engage in to modify or help clinicians to tailor effective and efficient treatment strategy. This proposed study focuses on one-carbon metabolism a key process for DNA methylation and DNA synthesis. One-carbon metabolism is crucial of BC prognosis because it not only provides methyl group for regulating expression of genes that have prognostic values (e.g. ER PR BRCA1 etc.) but also is a primary target for treatment of the disease (e.g. 5-FU methotrexate etc.). We propose to utilize the resources of the Long Island Breast Cancer Study Project a large population-based study consisting of approximately 1500 BC cases and approximately 1500 controls. We will examine the dietary intake of one-carbon-related micronutrients/compounds (e.g. folate methionine chioline B vitamins alcohol etc.) in relation to disease-free and overall survival of BC via the mechanism of promoter hypermethylation (presumably silencing) of the ER, PR and BRCA1 genes. We will also examine whether functional polymorphisms in one-carbon metabolism may influence survival of BC either through modifying the efficacy of chemotherapeutic drugs or influencing methylation of prognosis-related genes.