![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital and Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115
2To whom correspondence should be addressed. E-mail: edward.giovannucci{at}channing.harvard.edu.
Dietary folate influences DNA methylation, synthesis and repair. Aberrations in these DNA processes may enhance carcinogenesis, particularly in rapidly proliferative tissues such as the colorectal mucosa. DNA methylation abnormalities may influence the expression of cancer-related genes, and inadequate levels of folate may lead to uracil misincorporation into DNA and to chromosomal breaks. Folate deficiency enhances intestinal carcinogenesis in several animal models. An increasing number of epidemiologic studies indicate that higher intakes of folate either from dietary sources or from supplements may lower the risk of colorectal adenoma and cancer. More limited data also suggest that dietary methionine, which might also influence methylation, may have a similar protective role. High alcohol consumption, which has a strong antifolate effect, also has been related to higher risk of colorectal neoplasia. The deleterious effects of alcohol are accentuated when folate or methionine intake is low. Some evidence also suggests that the risk of colorectal neoplasia may vary according to genetic polymorphisms in methylenetetrahydrofolate reductase, an enzyme that is involved in folate metabolism. The cumulative data indicate that maintaining adequate folate levels may be important in lowering risk of colorectal cancer.
KEY WORDS: • epidemiology • folate • colorectal neoplasia • diet
This article has been cited by other articles:
|
|
 |
|
  K. Wu, E. A Platz, W. C Willett, C. S Fuchs, J. Selhub, B. A Rosner, D. J Hunter, and E. Giovannucci A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma Am. J. Clinical Nutrition, December 1, 2009; 90(6): 1623 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. F. Drake and G. A. Colditz Assessing Cancer Prevention Studies--A Matter of Time JAMA, November 18, 2009; 302(19): 2152 - 2153. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Keinan-Boker, N. Vin-Raviv, I. Liphshitz, S. Linn, and M. Barchana Cancer Incidence in Israeli Jewish Survivors of World War II J Natl Cancer Inst, November 4, 2009; 101(21): 1489 - 1500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chanson, L. D Parnell, E. D Ciappio, Z. Liu, J. W Crott, K. L Tucker, and J. B Mason Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are associated with altered DNA uracil concentrations in an urban Puerto Rican population Am. J. Clinical Nutrition, June 1, 2009; 89(6): 1927 - 1936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A K Lawrance, L Deng, and R Rozen Methylenetetrahydrofolate reductase deficiency and low dietary folate reduce tumorigenesis in Apcmin/+ mice Gut, June 1, 2009; 58(6): 805 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Garcia-Crespo, E. Knock, N. Jabado, and R. Rozen Intestinal Neoplasia Induced by Low Dietary Folate Is Associated with Altered Tumor Expression Profiles and Decreased Apoptosis in Mouse Normal Intestine J. Nutr., March 1, 2009; 139(3): 488 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Zhang, N. R. Cook, C. M. Albert, J. M. Gaziano, J. E. Buring, and J. E. Manson Effect of Combined Folic Acid, Vitamin B6, and Vitamin B12 on Cancer Risk in Women: A Randomized Trial JAMA, November 5, 2008; 300(17): 2012 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Wolpin, E. K. Wei, K. Ng, J. A. Meyerhardt, J. A. Chan, J. Selhub, E. L. Giovannucci, and C. S. Fuchs Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer J. Clin. Oncol., July 1, 2008; 26(19): 3222 - 3228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A D. Smith, Y.-I. Kim, and H. Refsum Is folic acid good for everyone? Am. J. Clinical Nutrition, March 1, 2008; 87(3): 517 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Koutros, Y. Zhang, Y. Zhu, S. T. Mayne, S. H. Zahm, T. R. Holford, B. P. Leaderer, P. Boyle, and T. Zheng Nutrients Contributing to One-Carbon Metabolism and Risk of Non-Hodgkin Lymphoma Subtypes Am. J. Epidemiol., February 1, 2008; 167(3): 287 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Liu, S.-W. Choi, J. W. Crott, M. K. Keyes, H. Jang, D. E. Smith, M. Kim, P. W. Laird, R. Bronson, and J. B. Mason Mild Depletion of Dietary Folate Combined with Other B Vitamins Alters Multiple Components of the Wnt Pathway in Mouse Colon J. Nutr., December 1, 2007; 137(12): 2701 - 2708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E Chiuve, E. L Giovannucci, S. E Hankinson, S. H Zeisel, L. W Dougherty, W. C Willett, and E. B Rimm The association between betaine and choline intakes and the plasma concentrations of homocysteine in women Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1073 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Ziegler and U. Lim One-Carbon Metabolism, Colorectal Carcinogenesis, Chemoprevention with Caution J Natl Cancer Inst, August 15, 2007; 99(16): 1214 - 1215. [Full Text] [PDF]
|
|
|
|
|
|
U. Ericson, E. Sonestedt, B. Gullberg, H. Olsson, and E. Wirfalt High folate intake is associated with lower breast cancer incidence in postmenopausal women in the Malmo Diet and Cancer cohort Am. J. Clinical Nutrition, August 1, 2007; 86(2): 434 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
C. M. Ulrich and J. D. Potter Folate and Cancer--Timing Is Everything JAMA, June 6, 2007; 297(21): 2408 - 2409. [Full Text] [PDF]
|
|
|
|
|
|
M. C. Reed, H. F. Nijhout, M. L. Neuhouser, J. F. Gregory III, B. Shane, S. J. James, A. Boynton, and C. M. Ulrich A Mathematical Model Gives Insights into Nutritional and Genetic Aspects of Folate-Mediated One-Carbon Metabolism J. Nutr., October 1, 2006; 136(10): 2653 - 2661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Kushi, T. Byers, C. Doyle, E. V. Bandera, M. McCullough, T. Gansler, K. S. Andrews, M. J. Thun, and The American Cancer Society 2006 Nutrition and Phy American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity CA Cancer J Clin, September 1, 2006; 56(5): 254 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Leopardi, F. Marcon, S. Caiola, A. Cafolla, E. Siniscalchi, A. Zijno, and R. Crebelli Effects of folic acid deficiency and MTHFR C677T polymorphism on spontaneous and radiation-induced micronuclei in human lymphocytes Mutagenesis, September 1, 2006; 21(5): 327 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. C. Larsson, N. Hakansson, E. Giovannucci, and A. Wolk Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst, March 15, 2006; 98(6): 407 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matsuo, H. Ito, K. Wakai, K. Hirose, T. Saito, T. Suzuki, T. Kato, T. Hirai, Y. Kanemitsu, H. Hamajima, et al. One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan Carcinogenesis, December 1, 2005; 26(12): 2164 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Davis and N. G. Hord Nutritional "Omics" Technologies for Elucidating the Role(s) of Bioactive Food Components in Colon Cancer Prevention J. Nutr., November 1, 2005; 135(11): 2694 - 2697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ulrich Nutrigenetics in Cancer Research--Folate Metabolism and Colorectal Cancer J. Nutr., November 1, 2005; 135(11): 2698 - 2702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
C. M. Ulrich, K. Curtin, W. Samowitz, J. Bigler, J. D. Potter, B. Caan, and M. L. Slattery MTHFR Variants Reduce the Risk of G:C->A:T Transition Mutations within the p53 Tumor Suppressor Gene in Colon Tumors J. Nutr., October 1, 2005; 135(10): 2462 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Senesse, M. Touvier, E. Kesse, J. Faivre, and M.-C. Boutron-Ruault Tobacco Use and Associations of {beta}-Carotene and Vitamin Intakes with Colorectal Adenoma Risk J. Nutr., October 1, 2005; 135(10): 2468 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. E Chiuve, E. L Giovannucci, S. E Hankinson, D. J Hunter, M. J Stampfer, W. C Willett, and E. B Rimm Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine Am. J. Clinical Nutrition, July 1, 2005; 82(1): 155 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fenech The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis Mutagenesis, July 1, 2005; 20(4): 255 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Wei, E. Giovannucci, J. Selhub, C. S. Fuchs, S. E. Hankinson, and J. Ma Plasma Vitamin B6 and the Risk of Colorectal Cancer and Adenoma in Women J Natl Cancer Inst, May 4, 2005; 97(9): 684 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 D. D. Potter, J. A. Murray, J. H. Donohue, L. J. Burgart, D. M. Nagorney, J. A. van Heerden, M. F. Plevak, A. R. Zinsmeister, and S. N. Thibodeau The Role of Defective Mismatch Repair in Small Bowel Adenocarcinoma in Celiac Disease Cancer Res., October 1, 2004; 64(19): 7073 - 7077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 G. P. Basten, M. H. Hill, S. J. Duthie, and H. J. Powers Effect of Folic Acid Supplementation on the Folate Status of Buccal Mucosa and Lymphocytes Cancer Epidemiol. Biomarkers Prev., July 1, 2004; 13(7): 1244 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Huycke and H. R. Gaskins Commensal Bacteria, Redox Stress, and Colorectal Cancer: Mechanisms and Models Experimental Biology and Medicine, July 1, 2004; 229(7): 586 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. H. Townsend, S. R. Davis, A. D. Mackey, and J. F. Gregory III Folate deprivation reduces homocysteine remethylation in a human intestinal epithelial cell culture model: role of serine in one-carbon donation Am J Physiol Gastrointest Liver Physiol, April 1, 2004; 286(4): G588 - G595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Kimura, K. Umegaki, M. Higuchi, P. Thomas, and M. Fenech Methylenetetrahydrofolate Reductase C677T Polymorphism, Folic Acid and Riboflavin Are Important Determinants of Genome Stability in Cultured Human Lymphocytes J. Nutr., January 1, 2004; 134(1): 48 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-I. Kim Role of Folate in Colon Cancer Development and Progression J. Nutr., November 1, 2003; 133(11): 3731S - 3739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. Lokk News and Views on Folate and Elderly Persons J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2003; 58(4): M354 - 361. [Abstract] [Full Text] [PDF]
|
|
