The investigators propose to examine prospectively the relation between iron status (intake, body stores, and genetic susceptibility for hemochromatosis) and risk of myocardial infarction (MI) and colorectal cancer in three large cohorts. Iron intake was assessed by semiquantitative food frequency questionnaire (SFFQ) in 1980 in the Nurses' Health Study (NHS, n=121,700 women) and in 1986 in the NHS and in the Health Professionals Follow-up Study (HPFS, n=51,529 men). Blood samples were collected in both of these cohorts: from the NHS in 1989-90 (n=32,825 women), and the HPFS in 1993-94 (n=18,000 men). In addition, samples also were collected from participants in the Physicians' Health Study in 1982 (PHS, n=14,916 men). These men and women initially free of cardiovascular disease and cancer and have been followed prospectively for the occurrence of cardiovascular disease and cancer. The investigators plan to assay the samples, in a nested case-control design, for biomarkers of body iron stores (iron, total iron binding capacity, ferritin) and genetic marker of hemochromatosis, an inherited disease of iron overload (C282Y, a missense mutation in HLA-H gene). The iron-CHD/cancer hypotheses have been supported by laboratory and animal studies, but findings from small, less comprehensive epidemiologic studies are inconsistent. They propose to evaluate the individual associations of intake, biomarker levels, and genotype with risk of MI and colorectal cancer, as well as the combined effects. Further, they will evaluate other dietary and lifestyle factors that may account for or modify the association between iron and MI/colorectal cancer. The ongoing three cohorts will provide high yield follow-up participation and high quality end-point verification in addition to information on important variables (e.g., smoking, vitamin supplement use, dietary factors) for the proposed study. These analyses will take advantage of existing blood banks of these well-characterized cohorts, and part of the plasma ferritin measurements (the NHS and PHS) are funded through other sources. The investigators state that hence, this application provides a well-focused, efficient cost-effective, and comprehensive approach to evaluate the hypothesized but unproven role of iron as a risk factor for future cardiovascular disease and cancer.
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