© 1993 by Oxford University Press
Journal of the National Cancer Institute, Vol. 85, No. 11, 875-883,
June 2, 1993
© 1993 Oxford University Press
Folate, Methionine, and Alcohol Intake and Risk of Colorectal Adenoma
Channing Laboratory, Department of Medicine, Harvard Medical School Boston, Mass Brigham Women's Hospital Boston, Mass
Channing Laboratory, Department of Medicine, Harvard Medical School; Brigham and Women's Hospital; and Department of Epidemiology, Harvard School of Public Health Boston, Mass
Department of Epidemiology, Harvard School of Public Health
Channing Laboratory, Department of Medicine, Harvard Medical School; Brigham and Women's Hospital; and Departments of Epidemiology and Nutrition, Harvard School of Public Health
Correspondence to: Edward Giovannucci, M.D., Channing Laboratory, 180 Longwood Ave., Boston, MA 02115.
Background: Reduced methylation of DNA may contribute to loss of the normal controls on proto-oncogene expression. In humans, hypomethylation of DNA has been observed in colorectal cancers and in their adenomatous polyp precursors. Accumulation of DNA methylation abnormalities, observed during progression of human colorectal neoplasia, may be influenced by certain dietary factors. The apparent protective effect of fresh fruits and vegetables, the major folate sources, on colorectal cancer incidence suggests that a methyldeficient diet contributes to occurrence of this malignancy. Low dietary folate and methionine and high intake of alcohol may reduce levels of S-adeno-sylmethionine, which is required for DNA methylation. Purpose: To determine if dietary factors that may influence methyl availability are related to colorectal adenomas, we prospectively examined the association of folate, methionine, and alcohol intakes and risk of colorectal adenoma. Methods: We assessed dietary intake for a 1-year period for women of the Nurses' Health Study, started in 1976, and for men of the Health Professionals Follow-up Study, started in 1986—using a semiquantitative food frequency questionnaire. Adenomatous polyps of the left colon or rectum were diagnosed in 564 of 15984 women who had had an endoscopy between 1980 and 1990 and in 331 of 9490 men who had undergone an endoscopy between 1986 and 1990. Results: High dietary folate was inversely associated with risk of colorectal adenoma in women (multivariate relative risk [RR] = 0.66; 95% confidence interval [CI] = 0.46–0.95 between high and low quintiles of intake) and in men (RR = 0.63; 95% CI = 0.41–0.98) after adjusting for age, family history, indications for endoscopy, history of previous endoscopy, total energy intake, saturated fat intake, dietary fiber, and body mass index. Relative to nondrinkers, drinkers of more than 30 g of alcohol daily (about two drinks) had an elevated risk of adenoma (in women, RR = 1.84, 95% CI = 1.19–2.86; in men, RR = 1.64, 95% CI = 0.92–2.93). Methionine intake was inversely associated with risk of adenomas 1 cm or larger (RR = 0.62; 95% CI = 0.46–0.85, combining men and women). Conclusions: Folate, alcohol, and methionine could influence methyl group availability, and a methyl-deficient diet may be linked to early stages of colorectal neoplasia. A dietary pattern that increases methyl availability could reduce incidence of colorectal cancer. Implications: These data support efforts to increase dietary folate in segments of the population having diets with low intakes of this nutrient. [J Natl Cancer Inst 85:875–884, 1993]
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S. M. Zhang, W. C. Willett, J. Selhub, D. J. Hunter, E. L. Giovannucci, M. D. Holmes, G. A. Colditz, and S. E. Hankinson Plasma Folate, Vitamin B6, Vitamin B12, Homocysteine, and Risk of Breast Cancer J Natl Cancer Inst, March 5, 2003; 95(5): 373 - 380. [Abstract] [Full Text] [PDF]
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J. B. Mason Biomarkers of Nutrient Exposure and Status in One-Carbon (Methyl) Metabolism J. Nutr., March 1, 2003; 133(3): 941S - 947. [Abstract] [Full Text] [PDF]
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 G. C. Rampersaud, G. P.A. Kauwell, and L. B. Bailey Folate: A Key to Optimizing Health and Reducing Disease Risk in the Elderly J. Am. Coll. Nutr., February 1, 2003; 22(1): 1 - 8. [Abstract] [Full Text] [PDF]
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M. L. Jones, T. Treloar, and P. F. Nixon Dietary Interactions Influence the Effects of Bovine Folate-Binding Protein on the Bioavailability of Tetrahydrofolates in Rats J. Nutr., February 1, 2003; 133(2): 489 - 495. [Abstract] [Full Text] [PDF]
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J. Trasler, L. Deng, S. Melnyk, I. Pogribny, F. Hiou-Tim, S. Sibani, C. Oakes, E. Li, S. J. James, and R. Rozen Impact of Dnmt1 deficiency, with and without low folate diets, on tumor numbers and DNA methylation in Min mice Carcinogenesis, January 1, 2003; 24(1): 39 - 45. [Abstract] [Full Text] [PDF]
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M. L McCullough, D. Feskanich, M. J Stampfer, E. L Giovannucci, E. B Rimm, F. B Hu, D. Spiegelman, D. J Hunter, G. A Colditz, and W. C Willett Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance Am. J. Clinical Nutrition, December 1, 2002; 76(6): 1261 - 1271. [Abstract] [Full Text] [PDF]
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T. Keku, R. Millikan, K. Worley, S. Winkel, A. Eaton, L. Biscocho, C. Martin, and R. Sandler 5,10-Methylenetetrahydrofolate Reductase Codon 677 and 1298 Polymorphisms and Colon Cancer in African Americans and Whites Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1611 - 1621. [Abstract] [Full Text] [PDF]
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C. Sachse, G. Smith, M. J.V. Wilkie, J. H. Barrett, R. Waxman, F. Sullivan, D. Forman, D. T. Bishop, and C.R. Wolf A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer Carcinogenesis, November 1, 2002; 23(11): 1839 - 1850. [Abstract] [Full Text] [PDF]
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M. L. Jones and P. F. Nixon Tetrahydrofolates Are Greatly Stabilized by Binding to Bovine Milk Folate-Binding Protein J. Nutr., September 1, 2002; 132(9): 2690 - 2694. [Abstract] [Full Text] [PDF]
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K Khosraviani, H P Weir, P Hamilton, J Moorehead, and K Williamson Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer Gut, August 1, 2002; 51(2): 195 - 199. [Abstract] [Full Text] [PDF]
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E. Giovannucci Epidemiologic Studies of Folate and Colorectal Neoplasia: a Review J. Nutr., August 1, 2002; 132(8): 2350S - 2355. [Abstract] [Full Text] [PDF]
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C. A. Cooney, A. A. Dave, and G. L. Wolff Maternal Methyl Supplements in Mice Affect Epigenetic Variation and DNA Methylation of Offspring J. Nutr., August 1, 2002; 132(8): 2393S - 2400. [Abstract] [Full Text] [PDF]
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P. S. Yan, C.-M. Chen, H. Shi, F. Rahmatpanah, S. H. Wei, and T. H.-M. Huang Applications of CpG Island Microarrays for High-Throughput Analysis of DNA Methylation J. Nutr., August 1, 2002; 132(8): 2430S - 2434. [Abstract] [Full Text] [PDF]
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M. B. Terry, A. I. Neugut, R. M. Bostick, R. S. Sandler, R. W. Haile, J. S. Jacobson, C. M. Fenoglio-Preiser, and J. D. Potter Risk Factors for Advanced Colorectal Adenomas: A Pooled Analysis Cancer Epidemiol. Biomarkers Prev., July 1, 2002; 11(7): 622 - 629. [Abstract] [Full Text] [PDF]
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C. S. Fuchs, W. C. Willett, G. A. Colditz, D. J. Hunter, M. J. Stampfer, F. E. Speizer, and E. L. Giovannucci The Influence of Folate and Multivitamin Use on the Familial Risk of Colon Cancer in Women Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 227 - 234. [Abstract] [Full Text] [PDF]
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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]
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S D Xiao, X J Meng, Y Shi, Y B Hu, S S Zhu, and C W Wang Interventional study of high dose folic acid in gastric carcinogenesis in beagles Gut, January 1, 2002; 50(1): 61 - 64. [Abstract] [Full Text] [PDF]
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K. W. Singletary and S. M. Gapstur Alcohol and Breast Cancer: Review of Epidemiologic and Experimental Evidence and Potential Mechanisms JAMA, November 7, 2001; 286(17): 2143 - 2151. [Abstract] [Full Text] [PDF]
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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]
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L. A. Poirier, C. K. Wise, R. R. Delongchamp, and R. Sinha Blood Determinations of S-Adenosylmethionine, S-Adenosylhomocysteine, and Homocysteine: Correlations with Diet Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 649 - 655. [Abstract] [Full Text] [PDF]
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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]
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K. M Koehler, R. N Baumgartner, P. J Garry, R. H Allen, S. P Stabler, and E. B Rimm Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use Am. J. Clinical Nutrition, March 1, 2001; 73(3): 628 - 637. [Abstract] [Full Text] [PDF]
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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]
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D. S. Michaud, D. Spiegelman, S. K. Clinton, E. B. Rimm, W. C. Willett, and E. Giovannucci Prospective Study of Dietary Supplements, Macronutrients, Micronutrients, and Risk of Bladder Cancer in US Men Am. J. Epidemiol., December 15, 2000; 152(12): 1145 - 1153. [Abstract] [Full Text] [PDF]
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C. M. Ulrich, J. Bigler, C. M. Velicer, E. A. Greene, F. M. Farin, and J. D. Potter Searching Expressed Sequence Tag Databases: Discovery and Confirmation of a Common Polymorphism in the Thymidylate Synthase Gene Cancer Epidemiol. Biomarkers Prev., December 1, 2000; 9(12): 1381 - 1385. [Abstract] [Full Text]
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M. L. Slattery, K. Curtin, K. Anderson, K.-N. Ma, S. Edwards, M. Leppert, J. Potter, D. Schaffer, and W. S. Samowitz Associations between Dietary Intake and Ki-ras Mutations in Colon Tumors: A Population-based Study Cancer Res., December 1, 2000; 60(24): 6935 - 6941. [Abstract] [Full Text]
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T. K. Murphy, E. E. Calle, C. Rodriguez, H. S. Kahn, and M. J. Thun Body Mass Index and Colon Cancer Mortality in a Large Prospective Study Am. J. Epidemiol., November 1, 2000; 152(9): 847 - 854. [Abstract] [Full Text] [PDF]
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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]
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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]
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 W. C. Willett Diet and Cancer Oncologist, October 1, 2000; 5(5): 393 - 404. [Abstract] [Full Text]
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A. J. Levine, K. D. Siegmund, C. M. Ervin, A. Diep, E. R. Lee, H. D. Frankl, and R. W. Haile The Methylenetetrahydrofolate Reductase 677C{->}T Polymorphism and Distal Colorectal Adenoma Risk Cancer Epidemiol. Biomarkers Prev., July 1, 2000; 9(7): 657 - 663. [Abstract] [Full Text]
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 P. A. Janne and R. J. Mayer Chemoprevention of Colorectal Cancer N. Engl. J. Med., June 29, 2000; 342(26): 1960 - 1968. [Full Text] [PDF]
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