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Radiology and Oncology

The Journal of Association of Radiology and Oncology

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Volume 44, Issue 2 (Jun 2010)

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Hyperhomocysteinemia and the role of B vitamins in cancer

Nadja Plazar
  • College of Health Care Izola, University of Primorska, Izola, Slovenia
/ Mihaela Jurdana
  • College of Health Care Izola, University of Primorska, Izola, Slovenia
Published Online: 2010-05-03 | DOI: https://doi.org/10.2478/v10019-010-0022-z

Hyperhomocysteinemia and the role of B vitamins in cancer

Background. Patients suffering from malignancies have increased complications due to corresponding cardiovascular diseases and risk factor for the development of venous thromboembolism. Epidemiological studies have shown that increased homocysteine plasma concentration (hyperhomocysteinemia) is related to a higher risk of coronary heart disease, stroke, peripheral vascular disease and malignancies. Homocysteine (tHcy) is an intermediate sulfurcontaining amino acid produced from methionine during processing of dietary proteins. The plasma homocysteine levels are strongly influenced by diet, as well as by genetic factors. Folic acid, vitamins B6 and B12 are dietary components which influence the plasma homocysteine levels the most. Several studies have found that high blood levels of B vitamins are related to the integrity and function of DNA, and, are at least related to lower concentration of homocysteine. Folate depletion has been found to change DNA methylation and DNA synthesis in both animal and human studies. Because of this critical role of folate, most studies including homocysteine have focused on these two actions.

Conclusions. Hyperhomocysteinemia proves to be the most common condition highly associated with both venous and arterial thrombosis in many cancer patients, while the associated pathophysiology has not been precisely established yet. Therefore, of current interest is the possible role of folate metabolism developing into a cancer initiating hyperhomocysteinemia. This review will discuss this possibility.

Keywords: homocysteine; hyperhomocysteinemia; B vitamins; cancer

  • Fassbender K, Orell M, Hennerici M. Plasma Homocyst(e)ine Concentrations in Cerebrovascular Disease. Stroke 1999; 30: 2224-38.

  • Sun CF, Haven TR, Wu TL, Tsao KC, Wu JT. Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. Clin Chim Acta 2002; 321: 55-62.

  • Trosseau A. Phlegmasia alba dolens. Clin de l'Hotel-Dieu de Paris 1865; 3: 654-712.

  • Debevec L, Jerič T, Kovač V, Sok M, Bitenc M. The progress in routine management of lung cancer patients. A comparative analysis of an institution in 1996 and 2006. Radiol Oncol 2009; 43: 47-53.

  • Rickles FR, Levine M, Edwards RL. Hemostatic alteration in cancer patients. Cancer Metastasis Rev 1992; 11: 237-48. [Crossref]

  • Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nut 2008; 87: 517-33.

  • Kim YI. Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut 2006; 55: 1387-89. [Crossref] [PubMed]

  • Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007; 297: 2351-59.

  • Hirsch S, Sanchez H, Albala C, de la Maza MP, Barrera G, Leiva L et al. Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroeneterol Hepatol 2009; 21: 436-39. [Crossref]

  • Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be iluminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 2007; 16: 1325-29. [Crossref]

  • Weisberg IS, Park E, Ballman KV, Berger P, Nunn M, Suh DS, et al. Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease. Atherosclerosis 2003; 167: 205-14.

  • Voet D, Voet JG. Biochemistry (2nd ed.). New York: John Wiley and Sons, Inc; 1995.

  • Ridker PM, Manson JE, Buring JE, Shih J, Matias M, Hennekens CH. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999; 281: 1817-21.

  • Stanger O, Herrmann W, Pietrzik K, Flower B, Geisel J, Dierkes J, et al. DACHLIGA Homocystein (German, Austrian and Swiss Homocysteine Society): Consensus paper on the regional clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 2003; 41: 1392-403.

  • de Bree A, van Dusseldorp M, Brouwer IA, Van het Hof KH, Steegers-Theunissen RPM. Folate intake in Europe: recommended, actual and desired intake. Eur J Clin Nutr 1997; 51: 643-60. [Crossref]

  • Herrmann W. The Importance of Hyperhomocysteinemia as a Risk Factor for Diseases: An Overview. Clin Chem Lab Med 2001; 39: 666-74. [PubMed]

  • Kachanov DY, Dobrenkov KV, Shamanskaya TV, Abdullaev RT, Inushkina EV, Savkova RF, et al. Solid tumors in young children in moscow Region of Russian Federation. Radiol Oncol 2008; 42: 39-44.

  • Fodinger M, Horl WH, Sunder-Plassmann G. Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol 2000; 13: 20-33. [PubMed]

  • Silaste ML, Rantala M, Sämpi M, Alfthan G, Ato A, Kasänieiemi A. Polimorphisms of key enzymes in homocysteine metabolism affect diet responsiveness of plasma homocysteine in healthy women. J Nutr 2001; 131: 2643-47.

  • Schriver RC, Beaudet AL, Sly WS, Valle D eds. The metabolic and molecular basis of inherited disease. New York: Mc-Graw-Hill; 1995. p: 1276-1319.

  • Heijer den M, Rosendaal FR, Blom HJ, Gerrits WBJ, Bös GMJ. Hyperhomocysteinemia and Venous Thrombosis: A Meta - analysis. Thromb Haemost 1998; 80: 874-7.

  • Biasioli S, Schiavon R. Homocysteine as a cardiovascular risk factor. Blood Purif 2000; 18: 177-82. [Crossref] [PubMed]

  • Ridker PM, Hennekens CH, Selhub J, Mletich JP, MalinoW MR, Tampfer J. Interrelation of hyperhomocysteinemia, factor V Leiden, and risk of venous thromboembolism. Circulation 1997; 95: 177-82.

  • Clarke R, Levington S, Donald A, Johnston C, Refsum H, Stratton I, et al. Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies. J Cardiovasc Risc 2001; 8: 396-9.

  • Hultberg B, Andersson A, Sterner G. Plasma homocysteine in renal failure. Clin Nephrol 1993; 40: 223-35.

  • Pettersson T, Friman C, Abrahamsson L, Nilsson B, Norberg B. Serum homocysteine and methylmalonic acid in patients with rheumatoid arthritis and cobalaminopenia. J Rheumatol 1998; 25: 859-63. [PubMed]

  • Bolander-Gouaille C. Focus on Homocysteine. Clinical conditions associated with hyperhomocysteinemia. New York: Springer-Verlag France, Heidelberg; 2001. p. 47-68.

  • Fiskerstrand T, Ueland PM, Refsum H. Response of the methionine synthase system to short-term culture with homocysteine and nitrous oxide and its relation to methionine dependence. Int J Cancer 1997; 72: 301-6. [Crossref] [PubMed]

  • Corona G, Toffoli G, Fabris M, Viel A, Zarrelli A, Donada C, et al. Homocysteine accumulation in human ovarian carcinoma ascitic/cystic fluids possibly caused by metabolic alteration of the methionine cycle in ovarian carcinoma cells. Eur J Cancer 1997; 33: 1284-90. [Crossref] [PubMed]

  • Poirier LA. Methyl group deficiency in hepatocarcinogenesis. Drug Metab Rev 1994; 26: 185-99. [Crossref] [PubMed]

  • Fenech MF, Dreosti IE, Rinaldi JR. Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis 1997; 18: 1329-36. [Crossref]

  • Falanga A, Barbui T, Rickles FR, Levine MN. Guidelines for clotting studies in cancer patients. For the Scientific and Standardization Committee of the Subcommittee on Haemostasis and Malignancy International Society of Thrombosis and Haemostasis. Thromb Haemost 1993; 70: 540-42. [PubMed]

  • Prandoni P. Venous thromboembolism risk and management in women with cancer and thrombophilia. Gen Med 2005; 2: S28-S34. [Crossref]

  • Kessler CM. The Link Between Cancer and Venous Thromboembolism: Review. Am J Clin Oncol 2009; 32(4 Suppl): S3-S7. [Crossref] [PubMed]

  • Dovsak T, Ihan A, Didanovic V, Kansky A, Hren Ihan NI. Influence of surgical treatment and radiotherapy of the advanced intraoral cancers on complete blood count, body mass index, liver enzymes and leukocyte CD64 expression. Radiol Oncol 2009; 43: 282-92.

  • Gatt A, Makris A, Cladd H, Burcombe RJ, Smith JM, Cooper P, et al. Hyperhomocysteinemia in women with advanced breast cancer. Int J Lab Hem 2007; 29: 421-5. [Crossref]

  • Hekim N, Ergen A, Yaylim I, Yilmaz H, Zeybek U, Oztürk O, et al. No association between methylenetetrahydrofolate reductase C677T polymorphism and breast cancer. Cell Biochem Funct 2007; 25: 115-7.

  • Jennings E. Folic acid as a cancer- preventing agent. Medical Hypotheses 1995; 45: 297-303. [Crossref] [PubMed]

  • Al-Awadi F, Yang M, Tan Y, Han Q, Li S, Hoffman RM. Human tumor growth in nude mice is associated with decreased plasma cysteine and homocysteine. Anticancer Res 2008; 28: 2541-4.

  • Kishi S, Griener J, Cheng C, Das S, Cook EH, Pei D, et al. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. J Clin Oncol 2003; 21: 3084-91. [PubMed] [Crossref]

  • Wu LL, Wu JT. Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta 2002; 322: 21-8. [PubMed] [Crossref]

  • Wirleitner B, Reider D, Ebner S, Böck G, Widner B, Jaeger M, et al. Monocyte-derived dendritic cells release neopterin. J Leukoc Biol 2002; 72: 1148-53. [PubMed]

  • Murr C, Bergant A, Widschwendter M, Heim K, Schröcksnadel H, Fuchs D. Neopterin is an independent prognostic variable in females with breast cancer. Clin Chem 1999; 45: 1998-2004. [PubMed]

  • Murr C, Fuith LC, Widner B, Wirleitner B, Baier-Bitterlich G, Fuchs D. Increased neopterin concentrations in patients with cancer: indicator of oxidative stress? Anticancer Res 1999; 19(3A): 1721-8. [PubMed]

  • Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci USA 1997; 94: 3290-5. [Crossref]

  • Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993; 270: 2693-8.

  • Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G. Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 1991; 20: 368-74. [PubMed] [Crossref]

  • Benito E, Stiggelbout A, Bosch FX, Obrador A, Kaldor J, Mulet M, et al. Nutritional factors in colorectal cancer risk: a case-control study in Majorca. Int J Cancer 1991; 49: 161-67. [Crossref]

  • Martinez MA. Diet and cancer prevention: the roles of observation and experimentation. Nat Rev Cancer 2008; 8: 694-703. [PubMed] [Crossref]

  • Perše M, Cerar A. [Physical activity and colorectal cancer]. [Slovenian]. Zdrav Vestn 2009; 78: 399-405.

  • Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 1975; 15: 617-31. [Crossref] [PubMed]

  • Jennings E. Apricots and oncogenes: on vegetables and cancer prevention. Cleveland, Ohio: McGuire & Beckley; 1993.

  • Akoglu B, Milovic V, Caspary WF and Faust D. Hyperproliferation of homocysteine-tretaed colon cancer cells is reversed by folate and 5-methyltetrahydrofolate. Eur J Nutr 2004; 43: 93-9. [Crossref]

  • James SJ, Cross DR, Miller BJ. Alterations in nucleotide pools in rats fed diets deficient in choline, methionine and/or folic acid. Carcinogenesis 1992; 13: 2471-74. [PubMed] [Crossref]

  • Kunz BA. Mutagenesis and deoxyribonucleotide pool imbalance. Mutat Res 1988; 200: 133-47.

  • Duthie SJ, Narayanan S, Brand GM, Pirie L, Grant G. Impact of folate deficiency on DNA stability. J Nutr 2002; 132(8 Suppl): 2444S-9S.

  • Kim YI, Shirwadkar S, Choi SW, Puchyr M, Wang Y, Mason JB. Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in rat colon. Gastroenterol 2000; 119: 151-61.

  • Zhang S, Hunter DJ, Hankinson SE, Giovannucci EL, Rosner BA, Colditz GA, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999; 281: 1632-7.

  • Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 2000; 92: 266-9. [Crossref] [PubMed]

  • Sellers TA, Kushi LH, Cerhan JR, Vierkant RA, Gapstur SM, Vachon CM, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 2001; 12: 420-8. [Crossref]

  • Willett WC. Nutritional epidemiology. New York: Oxford University Press; 1998.

  • Potischman N, Swanson CA, Coates RJ, Gammon MD, Brogan DR, Curtin J, et al. Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer. Int J Cancer 1999; 82: 315-21. [PubMed] [Crossref]

  • Nacci A, Dallan I, Bruschini L, Traino AC, Panicucci E, Bruschini P, et al. Plasma homocysteine, folate, and vitamin B12 levels in patients with laryngeal cancer. Arch Otolaryngol Head Neck Surg 2008; 134: 1328-33. [Crossref]

  • Strojan P. Cysteine cathepsins and stefins in head and neck cancer: an update of clinical studies. Radiol Oncol 2008; 42: 69-81.

  • Dahlin AM, Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Palmqvist R. Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study. Int J Cancer 2008; 122: 2057-61.

  • Friso S, Sang Woon C. The potential cocarcinogenic effect of vitamin B12. Clin Chem Lab Med 2005; 43: 1158-63.

  • Giovannucci E, Stampfer MJ, Colditz GA, Rimm EB, Trichopoulos D, Rosner BA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 1993; 85: 875-84. [Crossref] [PubMed]

  • Sofic A, Sehovic N, Beslic S, Prnjavorac B, Bilalovic N, Caluk J, et al. MR rectum imaging with ultra sound gel as instrumental contrast media in tubulovillous adenoma. Radiol Oncol 2008; 42: 136-42.

  • Baghurst PA, McMichael AJ, Slavotinek AH, Baghurst KI, Boyle P, Walker AM. A case-control study of diet and cancer of the pancreas. Am J Epidemiol 1991; 134: 167-79.

  • Graham S, Hellmann R, Marshall J, Freudenheim J, Vena J, Swanson M, et al. Nutritional epidemiology of postmenopausal breast cancer in western New York. Am J Epidemiol 1991; 134: 552-66. [PubMed]

  • Iscovich JM, Iscovich RB, Howe G, Shiboski S, Kaldor JM. A case-control study of diet and breast cancer in Argentina. Int J Cancer 1989; 44: 770-6. [PubMed] [Crossref]

  • Osterhues A, Holzgreve W, Michels KB. Shall we put the world on folate? Lancet 2009; 19: 959-61. [Crossref]

  • Ulrich CM, Potter JD. Folate and cancer: timing is everything. JAMA 2007; 297: 2408-9.

  • Shane B. Folate fortification: enough already? Am J Clin Nutr 2003; 77: 8-9. [PubMed]

  • Kalmbach RD, Choumenkovitch SF, Troen AM, D'Agostino R, Jacques PF, Selhub J. Circulating folic acid in plasma: relation to folic acid fortification. Am J Clin Nutr 2008; 88: 763-8. [PubMed]

About the article


Published Online: 2010-05-03

Published in Print: 2010-06-01



Citation Information: Radiology and Oncology, ISSN (Online) 1581-3207, ISSN (Print) 1318-2099, DOI: https://doi.org/10.2478/v10019-010-0022-z. Export Citation

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