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Folate and Colon Cancer: Data from the Nurses' Health Study

Am Fam Physician. 1999 Feb 15;59(4):994.

Folate is essential for the production of purines and pyrimidines, which are required for DNA synthesis. An inadequate supply of folate may lead to abnormalities in DNA synthesis or repair. Data from prospective studies of men suggest that an inadequate intake of folate may increase the risk of colon cancer. Giovannucci and associates examined the relationship between folate intake, both from supplements and from food, and the risk for colon cancer in women participating in the Nurses' Health Study.

The dietary cohort (88,756 women) in this longitudinal study was established in 1980 by eliciting information on a food-frequency questionnaire that included items on 61 foods and beverages, and the use of vitamin and mineral supplements. Similar but expanded questionnaires were obtained in 1984, 1986 and 1990. Participants also provided information on height and weight, physical activity, aspirin use, colonoscopic or sigmoidoscopic screening for colon cancer and parental history of colon cancer.

A total of 655 new cases of colorectal adenocarcinoma were confirmed in the cohort. Of these, 442 lesions were in the colon, 143 were in the rectum and 70 were at undetermined sites.

Analysis of the total, supplemental and dietary intake of folate in relation to the risk of colon cancer demonstrated that a higher (more than 400 mg per day) total intake of folate in 1980 was related to a lower risk for colon cancer in women as compared with the risk among women with an intake of 200 mg per day or less. When data were analyzed to determine the influence of other nutrients, including vitamins A, E, C and D, and calcium, none of these nutrients was significantly related to the risk of colon cancer. For folate obtained from food only, a nonsignificant inverse association was noted when long-term (15 years or more) supplement users were excluded. However, long-term multivitamin use was associated with a substantially lower risk of colon cancer across all levels of dietary folate.

According to the authors, the results indicate that the long-term use (for 15 years or more) of multivitamin supplements containing folic acid may decrease colon cancer risk by about 75 percent, consistent with the hypothesis that folate intake is the principal nutritional factor associated with risk reduction. The findings indicate that both dietary and supplemental intakes are beneficial. In view of the relationship between folic acid intake and prevention of neural tube defects, along with possible benefits in preventing cardiovascular disease, the observations from this study of folate intake and risk of colon cancer in women raise the question of whether a higher folate intake in the general population may be a worthwhile goal.

Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. October 1, 1998;129:517–24.


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