Dietary intake and metabolism of folate in relation to breast cancer risk

Folate intake may have important health consequences including a potential role in carcinogenesis through its involvement in DNA synthesis, repair, and methylation. The primary purpose of this dissertation was to evaluate the role of dietary folate intake and its interaction with MTHFR C677T polymorphism in breast cancer risk using data from a case-control study among Chinese women in Shanghai (Projects 2 & 3). A secondary purpose was to assess within-person variability of blood folate in the same population (Project 1). Blood samples from 29 women who donated quarterly blood samples over a 12 month period were assayed for plasma and RBC folate concentrations using a microbiological method. The within-person variability of these two biomarkers were moderate with CV of 12.1% and 2.9%, respectively suggesting that one spot measurement may reasonably characterize long-term folate status among women in Shanghai.; We evaluated the relationship between folate intake and breast cancer risk in the population-based Shanghai Breast Cancer Study (SBCS). Included in the analyses were the 1321 cases and 1382 controls who did not regularly use a B-vitamin supplement or drink alcohol. An inverse association between folate intake and breast cancer risk was observed. This relationship was especially apparent among subjects who consumed higher amounts of methionine, vitamin B12, or vitamin B6, all obligate cofactors for enzymes involved in folate metabolism.; Genomic DNA from 426 cases and 419 controls were assayed for the MTHFR C677T polymorphism. A reduced risk of breast cancer was associated with the MTHFR 677T polymorphism, particularly among those whose intake levels of folate were high.; This dissertation supports a role for folate in breast carcinogenesis and suggests that the effect of folate may be modified by MTHFR genotypes. Data for this dissertation also indicate that blood folate measured at one time point can be used in future epidemiological studies as an indicator of longer-term level of this nutrient in blood.