Cancer Causes & Control

, Volume 19, Issue 9, pp 1005–1007 | Cite as

Systemic folate status and risk of colorectal cancer

  • N. T. Brockton
Letter to the editor

In their recent study of plasma folate concentration and risk of colorectal cancer (CRC), Otani et al. [1] concluded that a folate-rich status did not reduce the risk of CRC. The authors discussed several limitations of their study, including the low response rate for donation of a blood sample (23% for male cohort participants), the relative merits of measuring plasma folate concentration (a rather transient measure compared to erythrocyte folate), the relevance of current rather than past folate status and the low number of folate-deficient subjects in their study population; these are all valid caveats in the interpretation of this study. However, the description of the impact of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms was inaccurate. The authors state that the homozygous variant genotype is associated with an increased risk of CRC and a reduced enzymatic activity; they cite the work of Ma et al. [2] to support these statements. Firstly, the direction of the...


Colorectal Cancer Folate Ulcerative Colitis Folate Intake Methylene Tetrahydrofolate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

10552_2008_9161_MOESM1_ESM.doc (66 kb)
(DOC 66 kb)


  1. 1.
    Otani T, Iwasaki M, Sasazuki S, Inoue M, Tsugane S (2008) Plasma folate and risk of colorectal cancer in a nested case-control study: the Japan Public Health Center-based prospective study. Cancer Cause Control 19:67–74 CrossRefGoogle Scholar
  2. 2.
    Ma J, Stampfer MJ, Giovannucci E et al (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 57:1098–1102PubMedGoogle Scholar
  3. 3.
    Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159:423–443PubMedCrossRefGoogle Scholar
  4. 4.
    Frosst P, Blom HJ, Milos R et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113PubMedCrossRefGoogle Scholar
  5. 5.
    Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML (1999) The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol 6:359–365PubMedCrossRefGoogle Scholar
  6. 6.
    Yamada K, Chen Z, Rozen R, Matthews RG (2001) Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci USA 98:14853–14858PubMedCrossRefGoogle Scholar
  7. 7.
    AICR/WCRF (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective. AICR 2007 Washington, DCGoogle Scholar
  8. 8.
    Lashner BA, Heidenreich PA, Su GL, Kane SV, Hanauer SB (1989) Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative-colitis —a case-control study. Gastroenterology 97:255–259PubMedGoogle Scholar
  9. 9.
    Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G (1991) Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 20:368–374PubMedCrossRefGoogle Scholar
  10. 10.
    Bollheimer LC, Buettner R, Kullmann A, Kullmann F (2005) Folate and its preventive potential in colorectal carcinogenesis. How strong is the biological and epidemiological evidence? Crit Rev Oncol Hematol 55:13–36PubMedCrossRefGoogle Scholar
  11. 11.
    Brockton NT (2006) Localized depletion: the key to colorectal cancer risk mediated by MTHFR genotype and folate? Cancer Causes Control 17:1005–1016PubMedCrossRefGoogle Scholar
  12. 12.
    Johanning GL, Heimburger DC, Piyathilake CJ (2002) DNA methylation and diet in cancer. J Nutr 132:3814S–3818SPubMedGoogle Scholar
  13. 13.
    Meenan J, O’Hallinan E, Lynch S et al (1996) Folate status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects. Gut 38:410–413PubMedCrossRefGoogle Scholar
  14. 14.
    Meenan J, O’Hallinan E, Scott J, Weir DG (1997) Epithelial cell folate depletion occurs in neoplastic but not adjacent normal colon mucosa. Gastroenterology 112:1168CrossRefGoogle Scholar
  15. 15.
    Weir DG, Scott JM (1998) Colonic mucosal folate concentrations and their association with colorectal cancer. Am J Clin Nutr 68:763–764PubMedGoogle Scholar
  16. 16.
    Alonso-Aperte E, Gonzalez MP, Poo-Prieto R, Varela-Moreiras G (2007) Folate status and S-adenosylmethionine//S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans. Eur J Clin Nutr 62:295–298PubMedCrossRefGoogle Scholar
  17. 17.
    Piyathilake CJ, Johanning GL, Macaluso M et al (2000) Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is associated with global DNA hypomethylation. Nutr Cancer 37:99–107PubMedCrossRefGoogle Scholar
  18. 18.
    Kim YI, Fawaz K, Knox T et al (1998) Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps. Am J Clin Nutr 68:866–872PubMedGoogle Scholar
  19. 19.
    Cravo ML, Albuquerque CM, Salazar de Sousa L et al (1998) Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Am J Gastroenterol 93:2060–2064PubMedCrossRefGoogle Scholar
  20. 20.
    Tomkins A (2003) Assessing micronutrient status in the presence of inflammation. J Nutr 133:1649S–1655SPubMedGoogle Scholar
  21. 21.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedCrossRefGoogle Scholar
  22. 22.
    Suh JR, Herbig AK, Stover PJ (2001) New perspectives on folate catabolism. Annu Rev Nutr 21:255–282PubMedCrossRefGoogle Scholar
  23. 23.
    Gloria L, Cravo M, Pinto A et al (1996) DNA hypomethylation and proliferative activity are increased in the rectal mucosa of patients with long-standing ulcerative colitis. Cancer 78:2300–2306PubMedCrossRefGoogle Scholar
  24. 24.
    Kim YI (2004) Folate, colorectal carcinogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen 44:10–25PubMedCrossRefGoogle Scholar
  25. 25.
    Botto LD, Yang Q (2000) 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 151:862–877PubMedGoogle Scholar
  26. 26.
    Kim YI (2004) Will mandatory folic acid fortification prevent or promote cancer? Am J Clin Nutr 80:1123–1128PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Division of Population Health & InformationAlberta Cancer BoardCalgaryCanada

Personalised recommendations