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Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study

Edward Giovannucci, MD, ScD; Meir J. Stampfer, MD, DrPH; Graham A. Colditz, MD, DrPH; David J. Hunter, MBBS, ScD; Charles Fuchs, MD, MPH; Bernard A. Rosner, PhD; Frank E. Speizer, MD; and Walter C. Willett, MD, DrPH

1 October 1998 | Volume 129 Issue 7 | Pages 517-524

Background: High intake of folate may reduce risk for colon cancer, but the dosage and duration relations and the impact of dietary compared with supplementary sources are not well understood.

Objective: To evaluate the relation between folate intake and incidence of colon cancer.

Design: Prospective cohort study.

Setting: 88 756 women from the Nurses' Health Study who were free of cancer in 1980 and provided updated assessments of diet, including multivitamin supplement use, from 1980 to 1994.

Patients: 442 women with new cases of colon cancer.

Measurements: Multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake.

Results: Higher energy-adjusted folate intake in 1980 was related to a lower risk for colon cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake >400 µg/d compared with intake 200 µg/d) after controlling for age; family history of colorectal cancer; aspirin use; smoking; body mass; physical activity; and intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A, C, D, and E and intake of calcium were also controlled for, results were similar. Women who used multivitamins containing folic acid had no benefit with respect to colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15 years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]), representing 15 instead of 68 new cases of colon cancer per 10 000 women 55 to 69 years of age. Folate from dietary sources alone was related to a modest reduction in risk for colon cancer, and the benefit of long-term multivitamin use was present across all levels of dietary intakes.

Conclusions: Long-term use of multivitamins may substantially reduce risk for colon cancer. This effect may be related to the folic acid contained in multivitamins.

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				D. Feskanich, V. Singh, W. C. Willett, and G. A. Colditz Vitamin A Intake and Hip Fractures Among Postmenopausal Women JAMA, January 2, 2002; 287(1): 47 - 54. [Abstract] [Full Text] [PDF]

				S. Sibani, S. Melnyk, I. P. Pogribny, W. Wang, F. Hiou-Tim, L. Deng, J. Trasler, S.J. James, and R. Rozen Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice Carcinogenesis, January 1, 2002; 23(1): 61 - 65. [Abstract] [Full Text] [PDF]

				M Bardou, S Montembault, V Giraud, A Balian, E Borotto, C Houdayer, F Capron, J-C Chaput, and S Naveau Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study Gut, January 1, 2002; 50(1): 38 - 42. [Abstract] [Full Text] [PDF]

				W. C. Willett and M. J. Stampfer What Vitamins Should I Be Taking, Doctor? N. Engl. J. Med., December 20, 2001; 345(25): 1819 - 1824. [Full Text] [PDF]

				M. J. Shrubsole, F. Jin, Q. Dai, X.-O. Shu, J. D. Potter, J. R. Hebert, Y.-T. Gao, and W. Zheng Dietary Folate Intake and Breast Cancer Risk: Results from the Shanghai Breast Cancer Study Cancer Res., October 1, 2001; 61(19): 7136 - 7141. [Abstract] [Full Text] [PDF]

				R A Sharma, A J Gescher, K J O'Byrne, and W P Steward Familiar drugs may prevent cancer Postgrad. Med. J., August 1, 2001; 77(910): 492 - 497. [Abstract] [Full Text] [PDF]

				K. B. Michels, E. Giovannucci, D. Feskanich, and W. C. Willett Response J Natl Cancer Inst, May 16, 2001; 93(10): 791 - 791. [Full Text] [PDF]

				E. J. Konings, H. H. Roomans, E. Dorant, R A. Goldbohm, W. H. Saris, and P. A van den Brandt Folate intake of the Dutch population according to newly established liquid chromatography data for foods Am. J. Clinical Nutrition, April 1, 2001; 73(4): 765 - 776. [Abstract] [Full Text] [PDF]

				R. Z. Stolzenberg-Solomon, P. Pietinen, M. J. Barrett, P. R. Taylor, J. Virtamo, and D. Albanes Dietary and Other Methyl-Group Availability Factors and Pancreatic Cancer Risk in a Cohort of Male Smokers Am. J. Epidemiol., April 1, 2001; 153(7): 680 - 687. [Abstract] [Full Text] [PDF]

				M. L. Slattery Does an Apple a Day Keep Breast Cancer Away? JAMA, February 14, 2001; 285(6): 799 - 801. [Full Text] [PDF]

				W. C. Willett Diet and Cancer: One View at the Start of the Millennium Cancer Epidemiol. Biomarkers Prev., January 1, 2001; 10(1): 3 - 8. [Abstract] [Full Text]

				J LITTLE Multivitamins, folate, and colon cancer Gut, January 1, 2001; 48(1): 12 - 13. [Full Text] [PDF]

				K. B. Michels, Edward Giovannucci, K. J. Joshipura, B. A. Rosner, M. J. Stampfer, C. S. Fuchs, G. A. Colditz, F. E. Speizer, and W. C. Willett Prospective Study of Fruit and Vegetable Consumption and Incidence of Colon and Rectal Cancers J Natl Cancer Inst, November 1, 2000; 92(21): 1740 - 1752. [Abstract] [Full Text] [PDF]

				E. A. Platz, S. E. Hankinson, B. W. Hollis, G. A. Colditz, D. J. Hunter, F. E. Speizer, and E. Giovannucci Plasma 1,25-Dihydroxy- and 25-Hydroxyvitamin D and Adenomatous Polyps of the Distal Colorectum Cancer Epidemiol. Biomarkers Prev., October 1, 2000; 9(10): 1059 - 1065. [Abstract] [Full Text]

				J. Song, A. Medline, J. B. Mason, S. Gallinger, and Y.-I. Kim Effects of Dietary Folate on Intestinal Tumorigenesis in the ApcMin Mouse Cancer Res., October 1, 2000; 60(19): 5434 - 5440. [Abstract] [Full Text]