Annals
Established in 1927 by the American College of Physicians
:
Advanced search
box Article
 arrow  Table of Contents                
space
 arrow  Full Text of this article Free
space
 arrow  Figures/Tables List
space
box Services
 arrow  Send comment/rapid response letter
space
 arrow  Notify a friend about this article
space
 arrow  Alert me when this article is cited
space
 arrow  Add to Personal Archive
space
 arrow  Download to Citation Manager
space
 arrow  ACP Search                        
space
 arrow  Get Permissions
space
box Google Scholar
 arrow  Search for Related Content
space
box PubMed
Articles in PubMed by Author:
  arrow  Giovannucci, E.
space
  arrow  Willett, W. C.
space
 arrow  Related Articles in PubMed
space
 arrow  PubMed Citation
space
 arrow  PubMed
space

ARTICLE

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

right arrow 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.




This article has been cited by other articles:


Home page
J. Nutr.Home page
S. de Vogel, V. Dindore, M. van Engeland, R. A. Goldbohm, P. A. van den Brandt, and M. P. Weijenberg
Dietary Folate, Methionine, Riboflavin, and Vitamin B-6 and Risk of Sporadic Colorectal Cancer
J. Nutr., December 1, 2008; 138(12): 2372 - 2378.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
E. S. Schernhammer, E. Giovannuccci, C. S. Fuchs, and S. Ogino
A Prospective Study of Dietary Folate and Vitamin B and Colon Cancer According to Microsatellite Instability and KRAS Mutational Status
Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2895 - 2898.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
Y.-I. Kim
Folic Acid Supplementation and Cancer Risk: Point
Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2220 - 2225.
[Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
J. C. Figueiredo, A. J. Levine, M. V. Grau, O. Midttun, P. M. Ueland, D. J. Ahnen, E. L. Barry, S. Tsang, D. Munroe, I. Ali, et al.
Vitamins B2, B6, and B12 and Risk of New Colorectal Adenomas in a Randomized Trial of Aspirin Use and Folic Acid Supplementation
Cancer Epidemiol. Biomarkers Prev., August 1, 2008; 17(8): 2136 - 2145.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
G. A. Colditz and D. M. Winn
Criteria for the Evaluation of Large Cohort Studies: An Application to the Nurses' Health Study
J Natl Cancer Inst, July 2, 2008; 100(13): 918 - 925.
[Abstract] [Full Text] [PDF]


Home page
Therapeutic Advances in GastroenterologyHome page
J. A. Abrams
Review: Chemoprevention of esophageal adenocarcinoma
Therapeutic Advances in Gastroenterology, July 1, 2008; 1(1): 7 - 18.
[Abstract] [PDF]


Home page
J. Nutr.Home page
A. Pompei, L. Cordisco, A. Amaretti, S. Zanoni, S. Raimondi, D. Matteuzzi, and M. Rossi
Administration of Folate-Producing Bifidobacteria Enhances Folate Status in Wistar Rats
J. Nutr., December 1, 2007; 137(12): 2742 - 2746.
[Abstract] [Full Text] [PDF]


Home page
cfpHome page
M. Ryan-Harshman and W. Aldoori
Diet and colorectal cancer: Review of the evidence
Can Fam Physician, November 1, 2007; 53(11): 1913 - 1920.
[Abstract] [Full Text] [PDF]


Home page
JAMAHome page
J. A. Meyerhardt, D. Niedzwiecki, D. Hollis, L. B. Saltz, F. B. Hu, R. J. Mayer, H. Nelson, R. Whittom, A. Hantel, J. Thomas, et al.
Association of Dietary Patterns With Cancer Recurrence and Survival in Patients With Stage III Colon Cancer
JAMA, August 15, 2007; 298(7): 754 - 764.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
A. Hazra, K. Wu, P. Kraft, C. S. Fuchs, E. L. Giovannucci, and D. J. Hunter
Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nurses' Health Study
Carcinogenesis, July 1, 2007; 28(7): 1510 - 1519.
[Abstract] [Full Text] [PDF]


Home page
BMJHome page
N. J Wald and G. P Oakley
Should folic acid fortification be mandatory? Yes
BMJ, June 16, 2007; 334(7606): 1252 - 1252.
[Full Text] [PDF]


Home page
JAMAHome page
B. F. Cole, J. A. Baron, R. S. Sandler, R. W. Haile, D. J. Ahnen, R. S. Bresalier, G. McKeown-Eyssen, R. W. Summers, R. I. Rothstein, C. A. Burke, et al.
Folic Acid for the Prevention of Colorectal Adenomas: A Randomized Clinical Trial
JAMA, June 6, 2007; 297(21): 2351 - 2359.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
K. Fairfield and M. Stampfer
Vitamin and mineral supplements for cancer prevention: issues and evidence
Am. J. Clinical Nutrition, January 1, 2007; 85(1): 289S - 292S.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
A. Koushik, P. Kraft, C. S. Fuchs, S. E. Hankinson, W. C. Willett, E. L. Giovannucci, and D. J. Hunter
Nonsynonymous Polymorphisms in Genes in the One-Carbon Metabolism Pathway and Associations with Colorectal Cancer
Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2408 - 2417.
[Abstract] [Full Text] [PDF]


Home page
Hum Mol GenetHome page
S. Ernest, M. Carter, H. Shao, A. Hosack, N. Lerner, C. Colmenares, D. S. Rosenblatt, Y.-H. Pao, M. E. Ross, and J. H. Nadeau
Parallel changes in metabolite and expression profiles in crooked-tail mutant and folate-reduced wild-type mice
Hum. Mol. Genet., December 1, 2006; 15(23): 3387 - 3393.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
B. N. Ames
Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage
PNAS, November 21, 2006; 103(47): 17589 - 17594.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
D. Schottenfeld and J. Beebe-Dimmer
Alleviating the Burden of Cancer: A Perspective on Advances, Challenges, and Future Directions.
Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2049 - 2055.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Public HealthHome page
T. G.K. Bentley, W. C. Willett, M. C. Weinstein, and K. M. Kuntz
Population-Level Changes in Folate Intake by Age, Gender, and Race/Ethnicity after Folic Acid Fortification
Am J Public Health, November 1, 2006; 96(11): 2040 - 2047.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
G. R. Wasson, A. P. McGlynn, H. McNulty, S. L. O'Reilly, V. J. McKelvey-Martin, G. McKerr, J. J. Strain, J. Scott, and C. S. Downes
Global DNA and p53 Region-Specific Hypomethylation in Human Colonic Cells Is Induced by Folate Depletion and Reversed by Folate Supplementation
J. Nutr., November 1, 2006; 136(11): 2748 - 2753.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
Y-I Kim
Folate: a magic bullet or a double edged sword for colorectal cancer prevention?
Gut, October 1, 2006; 55(10): 1387 - 1389.
[Full Text] [PDF]


Home page
GutHome page
B Van Guelpen, J Hultdin, I Johansson, G Hallmans, R Stenling, E Riboli, A Winkvist, and R Palmqvist
Low folate levels may protect against colorectal cancer
Gut, October 1, 2006; 55(10): 1461 - 1466.
[Abstract] [Full Text] [PDF]


Home page
Postgrad. Med. J.Home page
A Shenkin
Micronutrients in health and disease.
Postgrad. Med. J., September 1, 2006; 82(971): 559 - 567.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Niclot, Q. Pruvot, C. Besson, D. Savoy, E. Macintyre, G. Salles, N. Brousse, B. Varet, P. Landais, P. Taupin, et al.
Implication of the folate-methionine metabolism pathways in susceptibility to follicular lymphomas
Blood, July 1, 2006; 108(1): 278 - 285.
[Abstract] [Full Text] [PDF]


Home page
Am J EpidemiolHome page
S. S. Tworoger, J. L. Hecht, E. Giovannucci, and S. E. Hankinson
Intake of Folate and Related Nutrients in Relation to Risk of Epithelial Ovarian Cancer
Am. J. Epidemiol., June 15, 2006; 163(12): 1101 - 1111.
[Abstract] [Full Text] [PDF]


Home page
Endocr Relat CancerHome page
Z Attias, H Werner, and N Vaisman
Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent manner.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 571 - 581.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
F. Kamangar, G. M. Dores, and W. F. Anderson
Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the World
J. Clin. Oncol., May 10, 2006; 24(14): 2137 - 2150.
[Abstract] [Full Text] [PDF]


Home page
Am J EpidemiolHome page
S. M. Zhang, S. C. Moore, J. Lin, N. R. Cook, J. E. Manson, I-M. Lee, and J. E. Buring
Folate, Vitamin B6, Multivitamin Supplements, and Colorectal Cancer Risk in Women
Am. J. Epidemiol., January 15, 2006; 163(2): 108 - 115.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
Y.-I. Kim
Nutritional Epigenetics: Impact of Folate Deficiency on DNA Methylation and Colon Cancer Susceptibility
J. Nutr., November 1, 2005; 135(11): 2703 - 2709.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
E. Giovannucci and S. Ogino
DNA Methylation, Field Effects, and Colorectal Cancer
J Natl Cancer Inst, September 21, 2005; 97(18): 1317 - 1319.
[Full Text] [PDF]


Home page
ANN INTERN MEDHome page
G. M. Eisen and D. S. Weinberg
Narrative Review: Screening for Colorectal Cancer in Patients with a First-Degree Relative with Colonic Neoplasia
Ann Intern Med, August 2, 2005; 143(3): 190 - 198.
[Abstract] [Full Text] [PDF]


Home page
Nutr Clin PractHome page
M. T. Williams and N. G. Hord
The Role of Dietary Factors in Cancer Prevention: Beyond Fruits and Vegetables
Nutr Clin Pract, August 1, 2005; 20(4): 451 - 459.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Public HealthHome page
G. Sorensen, E. Barbeau, A. M. Stoddard, M. K. Hunt, K. Kaphingst, and L. Wallace
Promoting Behavior Change Among Working-Class, Multiethnic Workers: Results of the Healthy Directions--Small Business Study
Am J Public Health, August 1, 2005; 95(8): 1389 - 1395.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Public HealthHome page
K. M. Emmons, A. M. Stoddard, R. Fletcher, C. Gutheil, E. G. Suarez, R. Lobb, J. Weeks, and J. A. Bigby
Cancer Prevention Among Working Class, Multiethnic Adults: Results of the Healthy Directions-Health Centers Study
Am J Public Health, July 1, 2005; 95(7): 1200 - 1205.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
A. T. Chan, J. Ma, G. J. Tranah, E. L. Giovannucci, N. Rifai, D. J. Hunter, and C. S. Fuchs
Hemochromatosis Gene Mutations, Body Iron Stores, Dietary Iron, and Risk of Colorectal Adenoma in Women
J Natl Cancer Inst, June 15, 2005; 97(12): 917 - 926.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
F. L. Meyskens Jr. and E. Szabo
Diet and Cancer: The Disconnect Between Epidemiology and Randomized Clinical Trials
Cancer Epidemiol. Biomarkers Prev., June 1, 2005; 14(6): 1366 - 1369.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
K. M. Emmons, C. M. McBride, E. Puleo, K. I. Pollak, E. Clipp, K. Kuntz, B. H. Marcus, M. Napolitano, J. Onken, F. Farraye, et al.
Project PREVENT: A Randomized Trial to Reduce Multiple Behavioral Risk Factors for Colon Cancer
Cancer Epidemiol. Biomarkers Prev., June 1, 2005; 14(6): 1453 - 1459.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
L. Le Marchand, L. R. Wilkens, L. N. Kolonel, and B. E. Henderson
The MTHFR C677T Polymorphism and Colorectal Cancer: The Multiethnic Cohort Study
Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1198 - 1203.
[Abstract] [Full Text] [PDF]


Home page
GutHome page
M Pufulete, R Al-Ghnaniem, A Khushal, P Appleby, N Harris, S Gout, P W Emery, and T A B Sanders
Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma
Gut, May 1, 2005; 54(5): 648 - 653.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
Y.-I. Kim
Will mandatory folic acid fortification prevent or promote cancer?
Am. J. Clinical Nutrition, November 1, 2004; 80(5): 1123 - 1128.
[Abstract] [Full Text] [PDF]


Home page
CA Cancer J ClinHome page
R. Sifri, S. Gangadharappa, and L. S. Acheson
Identifying and Testing for Hereditary Susceptibility to Common Cancers
CA Cancer J Clin, November 1, 2004; 54(6): 309 - 326.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
B. N. Ames
Supplements and Tuning Up Metabolism
J. Nutr., November 1, 2004; 134(11): 3164S - 3168S.
[Full Text] [PDF]


Home page
BloodHome page
C. F. Skibola, M. S. Forrest, F. Coppede, L. Agana, A. Hubbard, M. T. Smith, P. M. Bracci, and E. A. Holly
Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma
Blood, October 1, 2004; 104(7): 2155 - 2162.
[Abstract] [Full Text] [PDF]


Home page
JAMAHome page
E. B. Rimm and M. J. Stampfer
Diet, Lifestyle, and Longevity--The Next Steps?
JAMA, September 22, 2004; 292(12): 1490 - 1492.
[Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. K. Nagothu, A. K. Rishi, R. Jaszewski, O. Kucuk, and A. P. N. Majumdar
Folic acid-mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells
Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G541 - G546.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
E. Giovannucci
Alcohol, One-Carbon Metabolism, and Colorectal Cancer: Recent Insights from Molecular Studies
J. Nutr., September 1, 2004; 134(9): 2475S - 2481S.
[Abstract] [Full Text] [PDF]


Home page
Am J EpidemiolHome page
H. Chen, S. M. Zhang, M. A. Schwarzschild, M. A. Hernan, G. Logroscino, W. C. Willett, and A. Ascherio
Folate Intake and Risk of Parkinson's Disease
Am. J. Epidemiol., August 15, 2004; 160(4): 368 - 375.
[Abstract] [Full Text] [PDF]


Home page
Am J EpidemiolHome page
H. G. Skinner, D. S. Michaud, E. L. Giovannucci, E. B. Rimm, M. J. Stampfer, W. C. Willett, G. A. Colditz, and C. S. Fuchs
A Prospective Study of Folate Intake and the Risk of Pancreatic Cancer in Men and Women
Am. J. Epidemiol., August 1, 2004; 160(3): 248 - 258.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
M. Roncales, M. Achon, F. Manzarbeitia, C. Maestro de las Casas, C. Ramirez, G. Varela-Moreiras, and J. Perez-Miguelsanz
Folic Acid Supplementation for 4 Weeks Affects Liver Morphology in Aged Rats
J. Nutr., May 1, 2004; 134(5): 1130 - 1133.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
T. Hossain, I. Rosenberg, J. Selhub, G. Kishore, R. Beachy, and K. Schubert
Enhancement of folates in plants through metabolic engineering
PNAS, April 6, 2004; 101(14): 5158 - 5163.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
M. E. Martinez, S. M Henning, and D. S Alberts
Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence
Am. J. Clinical Nutrition, April 1, 2004; 79(4): 691 - 697.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
Y.-I. Kim
Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer?
Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 511 - 519.
[Abstract] [Full Text] [PDF]


Home page
Arch OphthalmolHome page
J. A. Mares, T. L. La Rowe, and B. A. Blodi
Doctor, What Vitamins Should I Take for My Eyes?
Arch Ophthalmol, April 1, 2004; 122(4): 628 - 635.
[Full Text] [PDF]


Home page
Am J EpidemiolHome page
L. Sharp and J. Little
Polymorphisms in Genes Involved in Folate Metabolism and Colorectal Neoplasia: A HuGE Review
Am. J. Epidemiol., March 1, 2004; 159(5): 423 - 443.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
A. T. Chan, E. L. Giovannucci, E. S. Schernhammer, G. A. Colditz, D. J. Hunter, W. C. Willett, and C. S. Fuchs
A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma
Ann Intern Med, February 3, 2004; 140(3): 157 - 166.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
E. L. Goode, J. D. Potter, J. Bigler, and C. M. Ulrich
Methionine Synthase D919G Polymorphism, Folate Metabolism, and Colorectal Adenoma Risk
Cancer Epidemiol. Biomarkers Prev., January 1, 2004; 13(1): 157 - 162.
[Abstract] [Full Text] [PDF]


Home page
Am J EpidemiolHome page
E. White, R. E. Patterson, A. R. Kristal, M. Thornquist, I. King, A. L. Shattuck, I. Evans, J. Satia-Abouta, A. J. Littman, and J. D. Potter
VITamins And Lifestyle Cohort Study: Study Design and Characteristics of Supplement Users
Am. J. Epidemiol., January 1, 2004; 159(1): 83 - 93.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
M. Verwei, K. Arkbage, H. Mocking, R. Havenaar, and J. Groten
The Binding of Folic Acid and 5-Methyltetrahydrofolate to Folate-Binding Proteins during Gastric Passage Differs in a Dynamic In Vitro Gastrointestinal Model
J. Nutr., January 1, 2004; 134(1): 31 - 37.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
R. P Heaney
Long-latency deficiency disease: insights from calcium and vitamin D
Am. J. Clinical Nutrition, November 1, 2003; 78(5): 912 - 919.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
L. B. Bailey
Folate, Methyl-Related Nutrients, Alcohol, and the MTHFR 677C->T Polymorphism Affect Cancer Risk: Intake Recommendations
J. Nutr., November 1, 2003; 133(11): 3748S - 3753.
[Abstract] [Full Text] [PDF]