Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

摘要

The purpose is training in nutritional and molecular epidemiology to establish an independent investigator. The major hypothesis is that high folate intake is associated with a decreased breast cancer risk particularly among those with MTHFR, MTR, and MTRR polymorphisms. The specific aims are (1) methodological training in the analysis of gene-gene and gene-environment interactions by studying folate intake and metabolic gene polymorphisms in a population-based breast cancer case-control study, (2) training in cohort study methodology through designing and implementing a newly proposed nested case- control study of breast cancer to examine dietary and plasma folate, and metabolic gene polymorphisms, (3) nutrition and cancer biology coursework (4) field work of a breast cancer case-control study and (5) development of a grant proposal examining folate, global DNA methylation and uracil misincorporation in breast cancer risk. To date, the major results are the MTHFR 677TT genotype and low folate intake is associated with an increased risk of breast compared to high intake and the 677CC genotype. We also found 677CC was associated with poorer survival from breast cancer among women with late-stage disease who had survived at least one year post-diagnosis. MTR and MTRR genotypes were not significantly associated with breast cancer risk. The investigator has also completed coursework, training inmethodology,and field work experience.