Skip to main content

Folate and colo-rectal cancer risk

  • Peter Sanderson (a1), Elaine Stone (a1), Young-In Kim (a2), John C. Mathers (a3), Ellen Kampman (a4), C. Stephen Downes (a5), Kenneth R. Muir (a6) and John A. Baron (a7)...

The UK Food Standards Agency convened a group of expert scientists to review current research investigating folate and colo-rectal cancer risk. The workshop aimed to examine current research and establish research priorities. The timing of folate exposure with respect to carcinogenesis, as well as the dose and form of folate, were considered key issues for future research. Also, the need to study further the influence of genetically defined subgroups was highlighted for future research.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Folate and colo-rectal cancer risk
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Folate and colo-rectal cancer risk
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Folate and colo-rectal cancer risk
      Available formats
Corresponding author
*Corresponding author: Dr Elaine Stone, fax 020 7276 8996, email
Hide All
1Sanjoaquin MA, Allen N, Couto E, Roddam AW & Key TJ (2005) Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer 113, 825828.
2Larsson SC, Giovannucci E & Wolk A (2005) A prospective study of dietary folate intake and risk of colorectal cancer: modification by caffeine intake and cigarette smoking. Cancer Epidemiol Biomarkers Prev 14, 740743.
3Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Stenling R, Riboli E, Winkvist A & Palmqvist R (2006) Low folate levels may protect against colorectal cancer. Gut 55, 14611466.
4Zhang SM, Moore SC, Lin J, Cook NR, Manson JE, Lee IM & Buring JE (2006) Folate, Vitamin B6, Multivitamin Supplements, and Colorectal Cancer Risk in Women. Am J Epidemiol 163, 108115.
5Baron JA, Sandler RS, Haile RW, Mandel JS, Mott LA & Greenberg ER (1998) Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst 90, 5762.
6Giovannucci E, Stampfer MJ, Colditz GA, Rimm EB, Trichopoulos D, Rosner BA, Speizer FE & Willett WC (1993) Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 85, 875884.
7Martinez ME, Henning SM & Alberts DS (2004) Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence. Am J Clin Nutr 79, 691697.
8Sharp L & Little J (2004) Polymorphisms in Genes Involved in Folate Metabolism and Colorectal Neoplasia: A HuGE Review. Am J Epidemiol 159, 423443.
9Bingham SA, Norat T, Moskal A, et al. (2005) Is the association with fiber from foods in colorectal cancer confounded by folate intake? Cancer Epidemiol Biomarkers Prev 14, 15521556.
10Cravo ML, Mason JB, Dayal Y, Hutchinson M, Smith D, Selhub J & Rosenberg IH (1992) Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine-treated rats. Cancer Res 52, 50025006.
11Kim YI, Salomon RN, Graeme-Cook F, Choi SW, Smith DE, Dallal GE & Mason JB (1996) Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats. Gut 39, 732740.
12Wargovich MJ, Chen CD, Jimenez A, Steele VE, Velasco M, Stephens LC, Price R, Gray K & Kelloff GJ (1996) Aberrant crypts as a biomarker for colon cancer: evaluation of potential chemopreventive agents in the rat. Cancer Epidemiol Biomarkers Prev 5, 355360.
13Le Leu RK, Young GP & McIntosh GH (2000) Folate deficiency reduces the development of colorectal cancer in rats. Carcinogenesis 21, 22612265.
14Le Leu RK, Young GP & McIntosh GH (2000) Folate deficiency diminishes the occurrence of aberrant crypt foci in the rat colon but does not alter global DNA methylation status. J Gastroenterol Hepatol 15, 11581164.
15Wargovich MJ, Jimenez A, McKee K, Steele VE, Velasco M, Woods J, Price R, Gray K & Kelloff GJ (2000) Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis 21, 11491155.
16Bashir O, FitzGerald AJ & Goodlad RA (2004) Both suboptimal and elevated vitamin intake increase intestinal neoplasia and alter crypt fission in the ApcMin/+ mouse. Carcinogenesis 25, 15071515.
17Song J, Sohn KJ, Medline A, Ash C, Gallinger S & Kim YI (2000) Chemopreventive effects of dietary folate on intestinal polyps in Apc+/ − Msh2 − / −  mice. Cancer Res 60, 31913199.
18Song J, Medline A, Mason JB, Gallinger S & Kim YI (2000) Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. Cancer Res 60, 54345440.
19Lindzon GM, Medline A, Sohn KJ, Gallinger S, Croxford R & Kim YI (in press) Effect of folic acid supplementation on the progression of colorectal aberrant crypt foci. Proc Am Assoc Cancer Res.
20Jones PA & Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3, 415428.
21Feinberg AP, Ohlsson R & Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7, 2133.
22Duthie SJ, Narayanan S, Sharp L, Little J, Basten G & Powers H (2004) Folate, DNA stability and colo-rectal neoplasia. Proc Nutr Soc 63, 571578.
23van den Donk M, van Engeland M, Pellis L, Witteman BJM, Kok FJ, Keijer J & Kampman E (2007) Dietary folate intake in combination with MTHFR C677T genotype and promoter methylation of tumor suppressor and DNA repair genes in sporadic colorectal adenomas. Cancer Epidemiol Biomarkers Prev 16, 327333.
24Hubner RA, Muir KR, Liu JF, Sellick GS, Logan RFA, Grainge M, Armitage N, Chau I & Houlston RS& The United Kingdom Colorectal Adenoma Prevention Consortium (2006) Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence. Cancer Epidemiol Biomarkers Prev 15, 16071613.
25Quinlivan EP & Gregory JF III (2003) Effect of food fortification on folic acid intake in the United States. Am J Clin Nutr 77, 221225.
26Ulrich CM & Potter JD (2006) Folate supplementation: too much of a good thing? Cancer Epidemiol Biomarkers Prev 15, 189193.
27Mathers JC (2005) Reversal of DNA hypomethylation by folic acid supplements: possible role in colorectal cancer prevention. Gut 54, 579581.
28Kim YI, Baik HW, Fawaz K, Knox T, Lee YM, Norton R, Libby E & Mason JB (2001) Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol 96, 184195.
29Pufulete M, Al Ghnaniem R, Khushal A, Appleby P, Harris N, Gout S, Emery PW & Sanders TAB (2005) Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut 54, 648653.
30Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, Miller BJ, Henning SM & Swendseid ME (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128, 12041212.
31Rampersaud GC, Kauwell GP, Hutson AD, Cerda JJ & Bailey LB (2000) Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 72, 9981003.
32Shelnutt KP, Kauwell GP, Gregory JF III, Maneval DR, Quinlivan EP, Theriaque DW, Henderson GN & Bailey LB (2004) Methylenetetrahydrofolate reductase 677C–>T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 15, 554560.
33Basten GP, Duthie SJ, Pirie L, Vaughan N, Hill MH & Powers HJ (2006) Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. Br J Cancer 94, 19421947.
34Shen L, Kondo Y, Rosner GL, et al. (2005) MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 97, 13301338.
35Giovannucci E & Ogino S (2005) DNA methylation, field effects, and colorectal cancer. J Natl Cancer Inst 97, 13171319.
36Wright AJA, Finglas PM, Dainty JR, Wolfe CA, Hart DJ, Wright DM & Gregory JF (2005) Differential kinetic behavior and distribution for pteroylglutamic acid and reduced folates: a revised hypothesis of the primary site of PteGlu metabolism in humans. J Nutr 135, 619623.
37Kelly P, McPartlin J, Goggins M, Weir DG & Scott JM (1997) Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr 65, 17901795.
38Sweeney MR, McPartlin J, Weir DG, Daly L & Scott JM (2006) Postprandial serum folic acid response to multiple doses of folic acid in fortified bread. Br J Nutr 95, 145151.
39Troen AM, Mitchell B, Sorensen B, et al. (2006) Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 136, 189194.
40Imai K, Matsuyama S, Miyake S, Suga K & Nakachi K (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356, 17951799.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 10
Total number of PDF views: 44 *
Loading metrics...

Abstract views

Total abstract views: 101 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st January 2018. This data will be updated every 24 hours.