Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study
Publication: Annals of Internal Medicine
Volume 129, Number 7
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Abstract
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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References
1.
Glynn SA, Albanes D, Pletinen P, Brown CC, Rautalahti M, Tangrea JA, et al. Colorectal cancer and folate status: a nested case–control study among male smokers. Cancer Epidemiol Biomarkers Prev. 1996; 5:487-94.
2.
Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Willett WC. Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst. 1995; 87:265-73.
3.
Glynn S, Albanes D. Folate and cancer: a review of the literature. Nutr Cancer. 1994; 22:101-19.
4.
White E, Shannon JS, Patterson RE. Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epidemiol Biomarkers Prev. 1997; 6:769-74.
5.
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Hennekens CH, Speizer FE. Dietary fat and the risk of breast cancer. N Engl J Med. 1987; 316:22-8.
6.
Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985; 122:51-65.
7.
Colditz GA, Willett WC, Stampfer MJ, Sampson L, Rosner B, Hennekens CH, et al. The influence of age, relative weight, smoking, and alcohol intake on the reproducibility of a dietary questionnaire. Int J Epidemiol. 1987; 16:392-8.
8.
U.S. Department of Agriculture. Composition of foods-raw, processed, and prepared, 1963-1988. Agricultural Handbook No. 8 Series. Washington, DC: Department of Agriculture, US Gov Pr Office; 1989.
9.
Stampfer MJ, Willett WC, Speizer FE, Dysert DC, Lipnick R, Rosner B, et al. Test of the National Death Index. Am J Epidemiol. 1984; 119:837-9.
10.
U.S. Food and Drug Administration. Statement of general policy or interpretation. Subchapter B-food and food products, part 121-food additives. Federal Register. 1973; 38:20725-6.
11.
Willett WC, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol. 1986; 124:17-27.
12.
Cupples LA, D'Agostino RB, Anderson K, Kannel WB. Comparison of baseline and repeated measure covariate techniques in the Framingham Heart Study. Stat Med. 1988; 7:205-22.
13.
D'Agostino RB, Lee ML, Belanger AJ, Cupples LA, Anderson K, Kannel WB. Relation of pooled logistic regression to time dependent Cox regression analysis: the Framingham Heart Study. Stat Med. 1990; 9:1501-15.
14.
Benito E, Stiggelbout A, Bosch FX, Obrador A, Kaldor J, Mulet M, et al. Nutritional factors in colorectal cancer risk: a case–control study in Majorca. Int J Cancer. 1991; 49:161-7.
15.
Meyer F, White E. Alcohol and nutrients in relation to colon cancer in middle-aged adults. Am J Epidemiol. 1993; 138:225-36.
16.
Ferraroni M, La Vecchia C, D'Avanzo B, Negri E, Franceschi S, Decarli A. Selected micronutrient intake and the risk of colorectal cancer. Br J Cancer. 1994; 70:1150-5.
17.
Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G. Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol. 1991; 20:368-74.
18.
Ma J, Stampfer M, Giovannucci E, Artigas C, Hunter DJ, Fuchs C, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res. 1997; 57:1098-102.
19.
Bird CL, Swendseid ME, Witte JS, Shikany JM, Hunt IF, Frankl HD, et al. Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev. 1995; 4:709-14.
20.
Tseng M, Murray SC, Kupper LL, Sandler RS. Micronutrients and the risk of colorectal adenomas. Am J Epidemiol. 1996; 144:1005-14.
21.
Giovannucci E, Stampfer MJ, Colditz GA, Rimm EB, Trichopolous D, Rosner BA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst. 1993; 85:875-84.
22.
Benito E, Cabeza E, Moreno V, Obrador A, Bosch FX. Diet and colorectal adenomas: a case–control study in Majorca. Int J Cancer. 1993; 55:213-9.
23.
Paspatis GA, Kalafatis E, Oros L, Xourgias V, Koutsioumpa P, Karamanolis D. Folate status and adenomatous colonic polyps. A colonoscopically controlled study. Dis Colon Rectum. 1995; 38:64-7.
24.
Baron JA, Sandler RS, Haile RW, Mandel JS, Mott LA, Greenberg ER. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst. 1998; 90:57-62.
25.
Chu KC, Tarone RE, Chow WH, Hankey BF, Ries LA. Temporal patterns in colorectal cancer incidence, survival, and mortality from 1950 through 1990. J Natl Cancer Inst. 1994; 86:997-1006.
26.
Sturmer T, Glynn RJ, Lee IM, Manson JE, Buring JE, Hennekens CH. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study. Ann Intern Med. 1998; 128:713-20.
27.
Subar AF, Block G, James LD. Folate intake and food sources in the US population. Am J Clin Nutr. 1989; 50:508-16.
28.
Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med. 1993; 86:703-8.
29.
Bailey L, Wagner P, Christakis G, Davis C. Folacin and iron status of adolescents from low-income rural households. Nutr Res. 1982; 2:397-407.
30.
Senti FR, Pilsch SM. Analysis of folate data from the second National Health and Nutrition Examination Survey (NHANES II). J Nutr. 1985; 115:1398-402.
31.
Sauberlich H. Evaluation of folate nutrition in population groups. In: Picciano MF, Stokstad EL, Gregory JF 3d, eds. Folic Acid Metabolism in Health and Disease. New York: Wiley-Liss; 1990:211-35.
32.
Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991; 338:131-7.
33.
Gregory JF 3d. Bioavailability of folate. Eur J Clin Nutr. 1997; 51(Suppl 1):S54-9.
34.
Cuskelly GJ, McNulty H, Scott JM. Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects. Lancet. 1996; 347:657-9.
35.
Wickramasinghe S, Fida S. Bone marrow cells from vitamin B12- and folate-deficient patients misincorporate uracil into DNA. Blood. 1994; 83:1656-61.
36.
Weinberg G, Ullman B, Martin DW Jr. Mutator phenotypes in mammalian cell mutants with distinct biochemical defects and abnormal deoxyribonucleoside triphosphate pools. Proc Natl Acad Sci U S A. 1981; 78:2447-51.
37.
Meuth M. Role of deoxynucleoside triphosphate pools in the cytotoxic and mutagenic effects of DNA alkylating agents. Somatic Cell Genet. 1981; 7:89-102.
38.
Sutherland GR. The role of nucleotides in human fragile site expression. Mutat Res. 1988; 200:207-13.
39.
Fenech M, Rinaldi J. The relationship between micronuclei in human lymphocytes and plasma levels of vitamin C, vitamin E, vitamin B12, and folic acid. Carcinogenesis. 1994; 15:1405-11.
40.
Hunting DJ, Dresler SL. Dependence of u.v.-induced DNA excision repair on deoxyribonucleoside triphosphate concentrations in permeable human fibroblasts: a model for the inhibition of repair by hydroxyurea. Carcinogenesis. 1985; 6:1525-8.
41.
James SJ, Basnakian AG, Miller BJ. In vitro folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells. Cancer Res. 1994; 54:5075-80.
42.
Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997; 94:3290-5.
43.
Cravo M, Fidalgo P, Pereira A, Gouveia-Oliveira A, Chaves P, Selhub J, et al. DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev. 1994; 3:473-9.
44.
Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983; 301:89-92.
45.
Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science. 1985; 228:187-90.
46.
Feinberg AP, Gehrke CW, Kuo KC, Ehrlich M. Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 1988; 48:1159-61.
47.
Issa JP, Vertino PM, Wu J, Sazawal S, Celano P, Nelkin BD, et al. Increased cytosine DNA-methyltransferase activity during colon cancer progression. J Natl Cancer Inst. 1993; 85:1235-40.
48.
Makos M, Nelkin BD, Lerman MI, Latif F, Zbar B, Baylin SB. Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer. Proc Natl Acad Sci U S A. 1992; 89:1929-33.
49.
Chen J, Giovannucci E, Kelsey K, Rimm EB, Stampfer MJ, Colditz GA, et al. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 1996; 56:4862-4.
50.
Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase [Letter]. Nat Genet. 1995; 10:111-3.
51.
Goyette P, Sumner J, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet. 1994; 7:195-200.
52.
Rosner B, Spiegelman D, Willett WC. Correction of logistic regression relative risk estimates and confidence intervals for measurement error: the case of multiple covariates measured with error. Am J Epidemiol. 1990; 132:734-45.
53.
Oakley GP Jr. Let's increase folic acid fortification and include vitamin B-12 [Editorial]. Am J Clin Nutr. 1997; 65:1889-90.
54.
Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998; 279:359-64.
Information & Authors
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Published In
Annals of Internal Medicine
Volume 129 • Number 7 • 1 October 1998
Pages: 517 - 524
History
Published in issue: 1 October 1998
Published online: 15 August 2000
Keywords
Copyright
© 1998 American College of Physicians.
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Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study. Ann Intern Med.1998;129:517-524. doi:10.7326/0003-4819-129-7-199810010-00002
Multivitamin Use, Folate, and Colon Cancer in Women in the Nurses' Health Study. Ann Intern Med.1998;129:517-524. doi:10.7326/0003-4819-129-7-199810010-00002
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