Abstract
Folate and cobalamin (Vitamin B12) are two essential micronutrients involved in one-carbon metabolism, which affects heart disease, neural tube defects and cancer. Methylenetetrahydrofolate reductase, the key enzyme involved in one carbon metabolism produces methyl tetrahydrofolate from methylene tetrahydrofolate, which in turn donates methyl group to homocysteine to generate methionine. There exist two common low function polymorphic variants of the methylenetetrahydrofolate reductase gene involving nucleotides 677 C→T and 1298 A→C, which are associated with hyperhomocysteinemia. These polymorphisms are also linked with increased risk for certain cancers such as breast cancer and at the same time providing a protective effect on colorectal cancer. In this case control study, we have evaluated levels of folic acid, vitamin B12 and homocysteine in patients with colorectal cancer. Folate and homocysteine levels did not differ significantly between the two groups; however an increasing trend was noticed with increase in homocysteine levels. Vitamin B12 levels were increased in cases compared to control group.
Key words: Colorectal cancer, Folate, Vitamin B12, Homocysteine
Full Text
The Full Text of this article is available as a PDF (122.2 KB).
References
- 1.Das P.M., Singal R. DNA methylation and cancer. J Clin Oncol. 2004;22:4632–4642. doi: 10.1200/JCO.2004.07.151. [DOI] [PubMed] [Google Scholar]
- 2.Allen R.H., Stabler S.P., Savage D.G. Diagnosis of cobalamin deficiency I. Usefulness of serum methylamlonic acid and total homocysteine concentrations. Am J Hematol. 1990;34:90–98. doi: 10.1002/ajh.2830340204. [DOI] [PubMed] [Google Scholar]
- 3.Gershoni-Baruch R., Dagan E., Israeli D. Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. Eur J Cancer. 2000;36:2313–2316. doi: 10.1016/S0959-8049(00)00306-3. [DOI] [PubMed] [Google Scholar]
- 4.Miao X., Xing D., Tan W., Qi J., Lu W., Lin D. Susceptibility to gastric cardia adenocarcinoma and genetic polymorphisms in methylenetetrahydrofolate reductase in an at-risk chinese population. Cancer Epidemiol Biomarkers Prev. 2002;11:1454–1458. [PubMed] [Google Scholar]
- 5.Wiemels J.L., Smith R.N., Taylor G.M., Eden O.B., Alexander F.E., Greves M.F. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci. U S A. 2001;98:4004–4009. doi: 10.1073/pnas.061408298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chen J., Giovannucci E., Kelsey K., Rimm E.B., Stampfer M.J., Colditz G.A. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 1996;56:4862–4864. [PubMed] [Google Scholar]
- 7.Frantzen F., Faaren A.L., Aifheim I., Nordhei A.K. Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clin Chem. 1998;44(2):311–316. [PubMed] [Google Scholar]
- 8.Gutcho S., Mansbach L. Simultaneous radioassay of serum Vitamin B12 and Folic acid. Clin Chem. 1977;23(9):1609–1614. [PubMed] [Google Scholar]
- 9.Kim Y. I. Folate and carcinomgenesis: evidence, mechanisms and implications. J Nutr. 1999;10:62–88. doi: 10.1016/s0955-2863(98)00074-6. [DOI] [PubMed] [Google Scholar]
- 10.Jacob R.A., Gretz D.M., Taylor P.C., James S.J., Pogribny I.P., Miller B.J., et al. Moderate folate depletion increases plasma homocysteine and decreases lymphocytic DNA methylation in postmenopausal women. J Nutr. 1998;128:1204–1212. doi: 10.1093/jn/128.7.1204. [DOI] [PubMed] [Google Scholar]
- 11.Choi S.W., Mason J.B. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000;130:129–132. doi: 10.1093/jn/130.2.129. [DOI] [PubMed] [Google Scholar]
- 12.Blount B.C., Mack M.M., Wehr C.M., Hiatt R.A., Wang G., Wickramasinghe S.N., et al. Foalte deficiency causes uracil misincorporation into human DNA and chromosome brekage: Implication for cancer and neuronal damage. Proc Natl Acad Sci USA. 1997;94:3290–3295. doi: 10.1073/pnas.94.7.3290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Fenech M., Dreosti J.E., Rinaldi J. Folate, vitamin B12, homocysteine status and chrosome damage rate in lymphocytes of older men. Carcinogenesis. 1997;18:1329–1336. doi: 10.1093/carcin/18.7.1329. [DOI] [PubMed] [Google Scholar]
- 14.Fenech M., Aitken C., Rinaldi J. Folate, Vitamin B12 homocysteine status and DNA damage in young Australian adults. Carcinogenesis. 1998;19:1163–1171. doi: 10.1093/carcin/19.7.1163. [DOI] [PubMed] [Google Scholar]
- 15.Ma J., Stampfer M.J., Giovanucci E., Artigas C., Hunter D.J., Fuchs C., et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions and of colorectal cancer. Cancer Res. 1997;57:1098–1102. [PubMed] [Google Scholar]
- 16.Slattery M.L., Potter J.D., Samowitz W., Schaffer D., Leppert M. Methylenetetrahydrofolate reductase, diet and risk of colon cancer. Cancer Epidemiol Biomarkers Prev. 1999;8:513–518. [PubMed] [Google Scholar]
- 17.Skibola C.F., Smith M.T., Kane E., Roman E., Rollinson S., Cartwright R.A., et al. Polymorphisms in the methylene tetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA. 1999;96:12810–12815. doi: 10.1073/pnas.96.22.12810. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Wiemels J.L., Smith R.N., Tylor G.M., Eden O.B., Alexander F.E., Greaves M.F. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA. 2001;98:4004–4009. doi: 10.1073/pnas.061408298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Isotalo P.A., Wells G.A., Donnelly J.G. Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298 C mutations. Am J Human Genet. 2000;67:986–990. doi: 10.1086/303082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Kumar J., Das S.K., Sharma P., Karthikeyan G., Ramakrishnan L., Sengupta S. Homocysteine levels are associated with MTHFRA1298C polymorphism in Indian population. J Hum Genet. 2005;50:655–663. doi: 10.1007/s10038-005-0313-1. [DOI] [PubMed] [Google Scholar]
- 21.Powers H.J. Interaction among folate, riboflavin, genotype and cancer with reference to colorectal and cervical cancer. J Nutr. 2005;135(Suppl):2960–2966. doi: 10.1093/jn/135.12.2960S. [DOI] [PubMed] [Google Scholar]
- 22.Guelpen B., Hultdin J., Johansson I., Hallmans G., Stenling R., Riboli J., et al. Low folate levels may protect against colorectal cancer. Gut. 2006;55:1461–1466. doi: 10.1136/gut.2005.085480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Chou Y.C., Wu M.H., Yu J.C., Lee M.S., Yang T., Shih H.L. Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case — control study in Taiwan. Carcinogenesis. 2006;27:2295–2300. doi: 10.1093/carcin/bgl108. [DOI] [PubMed] [Google Scholar]
- 24.Marugame T., Tsuji E., Kiyohara C. Relation of plasma folate and Methylenetetrahydrofolate reductase C677T polymorphism to colorectal adenomas. Int J Epidemiol. 2003;32:64–66. doi: 10.1093/ije/dyg004. [DOI] [PubMed] [Google Scholar]
- 25.Vlajinac H.D., Marinkovic J.M., Ilic M.D., Koeev N.I. Diet and prostate cancer: a case —control study. Eur J Cancer. 1997;33:101–107. doi: 10.1016/S0959-8049(96)00373-5. [DOI] [PubMed] [Google Scholar]
- 26.Stevens V.L., McCullaigh M.L., Diver W.R. Use of multivitamins and prostate cancer mortality in a large cohort of US men. Cancer Causes Control. 2005;16:643–650. doi: 10.1007/s10552-005-0384-5. [DOI] [PubMed] [Google Scholar]
- 27.Gurdal-Yuksel E., Karadag M., Ozyardimci N., Kunt-Uzaslan A.E., Yarkin T. Cigarette smoking serum lipids, folate, and vitamin B12 in Lung cancer. J Environ Pathol Toxicol Oncol. 1996;15:161–167. [PubMed] [Google Scholar]
- 28.Hartman T.J., Woodco K., Stolzenberg-Solomen R., Virtamo J., Selhub J., Barrtt M.J., et al. Association of the B-vitamins, pyridoxal 5′-phosphate (B6), B12 and folate with lung cancer risk in older men. Am J Epidemiol. 2001;153:688–694. doi: 10.1093/aje/153.7.688. [DOI] [PubMed] [Google Scholar]
