| Summary: | BACKGROUND: Folate, a B-vitamin found primarily in fruits and vegetables, especially leafy greens, and other B-vitamins involved in folate metabolism are believed to protect against cancer and cardiovascular disease. Maintaining an adequate folate status ensures availability of methyl groups for DNA synthesis and for all methylation reactions in the body, and prevents the accumulation of homocysteine, a sulphur-containing amino acid that has been linked to cardiovascular disease. The aim of this thesis was to relate factors involved in folate metabolism to the risk of developing colorectal cancer (CRC), prostate cancer (PCa), stroke (ischemic and hemorrhagic), and acute myocardial infarction (AMI). SUBJECTS AND METHODS: These were nested case-referent studies, with 226 CRC, 254 PCa, 396 stroke (334 ischemic and 62 hemorrhagic), and 571 AMI cases, and double, matched referents from the population-based Northern Sweden Health and Disease Study. CRC RESULTS: A bell-shaped association was observed between plasma folate concentrations and the risk of CRC [multivariate odds ratio (OR) for the middle versus lowest quintile, 2.00 (95% CI 1.13-3.56)]. Homocysteine was not associated with CRC risk. A reduced risk was observed for the MTHFR 677C>T polymorphism [OR for TT versus CC, 0.41 (95% CI 0.19-0.85), Ptrend=0.062] that was independent of plasma folate status. Prediagnostic plasma folate concentrations were higher in cases with promoter hypermethylation in the p16 and/or hMLH1 tumor suppressor genes in CRC tissue compared to cases without promoter hypermethylation in these genes (P=0.025). PCa RESULTS: Increasing plasma levels of folate and vitamin B12 were associated with increased risk of PCa [OR for the highest versus lowest quartile, 1.60 (95% CI 1.03-2.49), Ptrend=0.02 for folate, and 2.63 (95% CI 1.61-4.29), Ptrend<0.001 for vitamin B12]. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance. In multivariate analyses, the risk estimate remained statistically ...
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