Colorectal adenomas are well-established precursors of cancer; by preventing the occurrence or growth of adenomas, we hope ultimately to prevent cancer. Thus, we propose to continue the prospective study of dietary determinants of colorectal adenomas in participants of the Nurses' Health Study and the Health Professionals Follow-Up Study. Specifically, we plan to conduct nested case-control analyses among cohort members who have completed one or more food frequency questionnaires and have provided a blood specimen. Cases will be 3,100 projected men and women with a first diagnosis of colorectal adenoma between 1,980 and 2000, and non-cases will be those who have undergone a sigmoidoscopy or a colonoscopy negative for adenomas during the same time interval. We will obtain pathology reports to confirm the diagnosis of adenomatous polyp for all cases, and record anatomic site and polyp size. Using estimated nutrient intake and biochemical measures based on archived blood, we will address the hypothesis that intake or biomarkers of folic acid interact with methionine and alcohol consumption, and with a genetic polymorphism associated with low activity of methylene tetrahydrofolate reductase, to modulate risk of colorectal adenoma. We will examine whether higher intake and higher plasma levels of vitamin D reduce colorectal adenoma risk, particularly in the presence of known polymorphisms of the vitamin D receptor gene which correspond to lower transactivation of the vitamin D stimulus. We will also examine the hypothesis that the adenoma. growth-promoting influence of high body mass, abdominal distribution of obesity, and physical inactivity is mediated through insulin and insulin- like growth factor levels, and will examine specific components of a high red meat-low fiber or vegetable dietary pattern to assess why this diet increases the risk of adenoma. These hypotheses will also be examined for recurrent adenomas. stratified analyses and multiple logistic regression will be used to control for potential confounding and to examine effect modification by obesity, smoking, exercise, specific genetic factors, and family history-of colorectal cancer, as well as by other nutrients.
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