Skip to main content

Advertisement

SpringerLink
Log in

A literature review of MTHFR (C677T and A1298C polymorphisms) and cancer risk

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

5,10-Methlenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism. This enzyme is mapped on chromosome 1, which is located at the end of the short arm (1p36.3). The C677T and A1298C are MTHFR polymorphisms that decrease in vitro MTHFR enzyme activity. Folate metabolism plays a key role in cell metabolism. These reactions are associated with purine–pyrimidine synthesis: DNA, RNA, and protein methylation. Polymorphism is also a factor in biodiversity, and be affected by ethnic heritage and geographic locale. In the case of unknown outcomes, not only should all geographical regions be investigated to ascertain biodiversity, but all populations as well to fully understand the variations in the effect. PUBMED was searched from January 2006 to December 2011 to develop an investigatory pursuit strategy. MTHFR, cancer, C677T, A1298C, and polymorphisms were key words used to focus the search. The literature review included all published relevant cancer types and MTHFR polymorphisms for that 5 years period. All selected polymorphisms data for cancer types was listed in tables for easy access and retrieval.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schwann B, Rozen R (2001) Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics 1(3):189–201

    Article  Google Scholar 

  2. Goyette P, Pai A, Milos R et al (1998) Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 9(8):571–582

    Article  Google Scholar 

  3. Goyette P, Rozen R (2000) The thermolabile variant 677C→T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. Hum Mutat 16(2):132–138

    Article  PubMed  CAS  Google Scholar 

  4. Robien K, Ulrich CM (2003) 5,10-Methylenetetrahydrofolate reductase polymorphisms and leukemia risk: a HuGE minireview. Am J Epidemiol 157(7):571–582

    Article  PubMed  Google Scholar 

  5. Yang QH, Botto LD, Gallagher M et al (2008) Prevalence and effects of gene–gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank. Am J Clin Nutr 88(1):232–246

    PubMed  CAS  Google Scholar 

  6. Boushey CJ, Beresford SA, Omenn GS et al (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 274(13):1049–1057

    Article  PubMed  CAS  Google Scholar 

  7. Ueland PM, Refsum H, Stabler SP et al (1993) Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 39(9):1764–1779

    PubMed  CAS  Google Scholar 

  8. Sazci A, Ergül E, Güzelhan Y et al (2003) Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Brain Res Mol Brain Res 117(1):104–107

    Article  PubMed  CAS  Google Scholar 

  9. Kupferminc MJ, Eldor A, Steinman N et al (1999) Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 340(1):9–13

    Article  PubMed  CAS  Google Scholar 

  10. Mills JL, Kirke PN, Molloy AM et al (1999) Methylenetetrahydrofolate reductase thermolabile variant and oral clefts. Am J Med Genet 86(1):71–74

    Article  PubMed  CAS  Google Scholar 

  11. Wenstrom KD, Johanning GL, Johnston KE et al (2001) Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations. Am J Obstet Gynecol 184(5):806–812

    Article  PubMed  CAS  Google Scholar 

  12. Qiu LX, Zhang J, Li WH et al (2011) Lack of association between methlenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility. Mol Biol Rep 38(4):2295–2299

    Article  PubMed  CAS  Google Scholar 

  13. Mohammad NS, Yedluri R, Addepalli P et al (2011) Aberrations in one-carbon metabolism induce oxidative DNA damage in sporadic breast cancer. Mol Cell Biochem 349(1–2):159–167

    Article  PubMed  CAS  Google Scholar 

  14. Huang MY, Wang YH, Chen FM et al (2008) Multiple genetic polymorphisms of GSTP1 313AG, MDR1 3435CC, and MTHFR 677CC highly correlated with early relapse of breast cancer patients in Taiwan. Ann Surg Oncol 15(3):872–880

    Article  PubMed  Google Scholar 

  15. Alshatwi AA (2010) Breast cancer risk, dietary intake and methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms. Food Chem Toxicol 48(7):1881–1885

    Article  PubMed  CAS  Google Scholar 

  16. Perel’muter VM, Zav’ialova MV, Vtorushin SV et al (2008) Genetic and clinical and pathological characteristics of breast cancer in premenopausal and postmenopausal women. Adv Gerontol 21(4):643–653

    PubMed  Google Scholar 

  17. Suzuki T, Matsuo K, Hirose K et al (2008) One-carbon metabolism-related gene polymorphisms and risk of breast cancer. Carcinogenesis 29(2):356–362

    Article  PubMed  CAS  Google Scholar 

  18. Maruti SS, Ulrich CM, Jupe ER et al (2009) MTHFR C677T and postmenopausal breast cancer risk by intakes of one-carbon metabolism nutrients: a nested case-control study. Breast Cancer Res 11(6):R91

    Article  PubMed  CAS  Google Scholar 

  19. Ericson UC, Ivarsson MI, Sonestedt E et al (2009) Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele. Am J Clin Nutr 90(5):1380–1389

    Article  PubMed  CAS  Google Scholar 

  20. Batschauer AP, Cruz NG, Oliveira VC et al (2011) HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women. Mol Cell Biochem 357(1–2):247–253

    Article  PubMed  CAS  Google Scholar 

  21. Prasad VV, Wilkhoo H (2011) Association of the functional polymorphism C677T in the methylenetetrahydrofolate reductase gene with colorectal, thyroid, breast, ovarian and cervical cancers. Onkologie 34(8–9):422–426

    Article  PubMed  CAS  Google Scholar 

  22. Eroglu A, Karabıyık A, Akar N (2012) The association of protease activated receptor 1 gene -506 I/D polymorphism with disease-free survival in breast cancer patients. Ann Surg Oncol 19(4):1365–1369

    Article  PubMed  Google Scholar 

  23. Ziva Cerne J, Stegel V, Gersak K et al (2011) Lack of association between methylenetetrahydrofolate reductase genetic polymorphisms and postmenopausal breast cancer risk. Mol Med Report 4(1):175–179

    PubMed  Google Scholar 

  24. Knechtel G, Hofmann G, Gerger A et al (2010) Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer. J Cancer Res Clin Oncol 136(12):1813–1819

    Article  PubMed  CAS  Google Scholar 

  25. Xu X, Gammon MD, Wetmur JG et al (2008) B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer. Cancer Epidemiol Biomarkers Prev 17(8):2109–2116

    Article  PubMed  CAS  Google Scholar 

  26. Lewis SJ, Harbord RM, Harris R et al (2006) Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst 98(22):1607–1622

    Article  PubMed  CAS  Google Scholar 

  27. Hekim N, Ergen A, Yaylim I et al (2007) No association between methylenetetrahydrofolate reductase C677T polymorphism and breast cancer. Cell Biochem Funct 25(1):115–117

    Article  PubMed  CAS  Google Scholar 

  28. Yu CP, Wu MH, Chou YC et al (2007) Breast cancer risk associated with multigenotypic polymorphisms in folate-metabolizing genes: a nested case-control study in Taiwan. Anticancer Res 27(3B):1727–1732

    PubMed  CAS  Google Scholar 

  29. Sangrajrang S, Sato Y, Sakamoto H et al (2010) Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case-control study in Thai women. Breast Cancer Res Treat 123(3):885–893

    Article  PubMed  CAS  Google Scholar 

  30. Tao MH, Shields PG, Nie J et al (2009) DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR. Cancer Epidemiol Biomarkers Prev 18(3):998–1002

    Article  PubMed  CAS  Google Scholar 

  31. Martin YN, Olson JE, Ingle JN et al (2006) Methylenetetrahydrofolate reductase haplotype tag single-nucleotide polymorphisms and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15(11):2322–2324

    Article  PubMed  CAS  Google Scholar 

  32. Vaĭner AS, Boiarskikh UA, Voronina EN et al (2010) Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR, C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer in West Siberian Region of Russia. Mol Biol 44(5):816–823

    Google Scholar 

  33. Ma E, Iwasaki M, Kobayashi M et al (2009) Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan. Nutr Cancer 61(4):447–456

    Article  PubMed  CAS  Google Scholar 

  34. Ferroni P, Palmirotta R, Martini F et al (2009) Determinants of homocysteine levels in colorectal and breast cancer patients. Anticancer Res 29(10):4131–4138

    PubMed  CAS  Google Scholar 

  35. Beetstra S, Suthers G, Dhillon V et al (2008) Methionine-dependence phenotype in the de novo pathway in BRCA1 and BRCA2 mutation carriers with and without breast cancer. Cancer Epidemiol Biomarkers Prev 17(10):2565–2571

    Article  PubMed  CAS  Google Scholar 

  36. Kotsopoulos J, Zhang WW, Zhang S et al (2008) Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer. Breast Cancer Res Treat 112(3):585–593

    Article  PubMed  CAS  Google Scholar 

  37. Mir MM, Dar JA, Dar NA et al (2008) Combined impact of polymorphism of folate metabolism genes; glutamate carboxypeptidase, methylene tetrahydrofolate reductase and methionine synthase reductase on breast cancer susceptibility in Kashmiri women. Int J Health Sci 2(1):3–14

    Google Scholar 

  38. Guillem VM, Collado M, Terol MJ et al (2007) Role of MTHFR (677, 1298) haplotype in the risk of devoloping secondary leukemia after treatment of breast cancer and hematological malignancies. Leukemia 21(7):1413–1422

    Article  PubMed  CAS  Google Scholar 

  39. Martin DN, Boersma BJ, Howe TM et al (2006) Association of MTHFR gene polymorphisms with breast cancer survival. BMC Cancer 6:257

    Article  PubMed  CAS  Google Scholar 

  40. Jakubowska A, Gronwald J, Menkiszak J et al (2007) Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks. Breast Cancer Res Treat 104(3):299–308

    Article  PubMed  CAS  Google Scholar 

  41. Chou YC, Wu MH, Yu JC et al (2006) Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan. Carcinogenesis 27(11):2295–2300

    Article  PubMed  CAS  Google Scholar 

  42. Stevens VL, McCullough ML, Pavluck AL et al (2007) Association of polymorphisms in one-carbon metabolism genes and postmenopausal breast cancer incidence. Cancer Epidemiol Biomarkers Prev 16(6):1140–1147

    Article  PubMed  CAS  Google Scholar 

  43. Pepe C, Guidugli L, Sensi E et al (2007) Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers. Breast Cancer Res Treat 103(1):29–36

    Article  PubMed  CAS  Google Scholar 

  44. Ericson U, Sonestedt E, Ivarsson MI et al (2009) Folate intake, methylenetetrahydrofolate reductase polymorphisms, and breast cancer risk in women from the Malmö Diet and Cancer cohort. Cancer Epidemiol Biomarkers Prev 18(4):1101–1110

    Article  PubMed  CAS  Google Scholar 

  45. Gao CM, Tang JH, Cao HX et al (2009) MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women. J Hum Genet 54(7):414–418

    Article  PubMed  CAS  Google Scholar 

  46. Papandreou CN, Doxani C, Zdoukopoulos N et al (2012) Evidence of association between methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a candidate gene-association study in a South-eastern European population. DNA Cell Biol 31(2):193–198

    Article  PubMed  CAS  Google Scholar 

  47. Kwak SY, Kim UK, Cho HJ et al (2008) Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms as risk factors for hepatocellular carcinoma in a Korean population. Anticancer Res 28(5A):2807–2811

    PubMed  CAS  Google Scholar 

  48. Cui LH, Song Y, Si H et al (2011) Folate metabolism-related gene polymorphisms and susceptibility to primary liver cancer in North China. Med Oncol. doi:10.1007/s12032-011-0066-y

    Google Scholar 

  49. Mu LN, Cao W, Zhang ZF et al (2007) Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary hepatocellular carcinoma (HCC) in a Chinese population. Cancer Causes Control 18(6):665–675

    Article  PubMed  Google Scholar 

  50. Zhu ZZ, Cong WM, Liu SF et al (2006) A study on the association of MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 14(3):196–198

    PubMed  Google Scholar 

  51. Suzuki T, Matsuo K, Sawaki A et al (2008) Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev 17(10):2742–2747

    Article  PubMed  CAS  Google Scholar 

  52. Nisevic I, Dinic J, Nikolic A et al (2008) MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma. Cell Biochem Funct 26(6):659–663

    Article  PubMed  CAS  Google Scholar 

  53. Wang L, Lin DX, Lu XH et al (2006) Study on the relations between genetic polymorphisms in methylenetetrahydrofolate reductase, methionine synthase and the risk of pancreatic cancer. Zhonghua Liu Xing Bing Xue Za Zhi 27(1):50–54

    PubMed  Google Scholar 

  54. Qin JM, Wang XM, Chen B et al (2008) Study on the ingestion of folate and polymorphism of MTHFR C677T with esophageal cancer in Xinjiang Kazakh. Zhonghua Liu Xing Bing Xue Za Zhi 29(1):30–33

    PubMed  CAS  Google Scholar 

  55. Liu YX, Wang B, Wan MH et al (2011) Meta-analysis of the relationship between the methylenetetrahydrofolate reductase C677T genetic polymorphism, folate intake and esophageal cancer. Asian Pac J Cancer Prev 12(1):247–252

    PubMed  Google Scholar 

  56. Qin JM, Yang L, Chen B et al (2008) Interaction of methylenetetrahydrofolate reductase C677T, cytochrome P450E1 polymorphism and environment factors in esophageal cancer in Kazakh population. World J Gastroenterol 14(45):6986–6992

    Article  PubMed  CAS  Google Scholar 

  57. Li D, Diao Y, Li H et al (2008) Association of the polymorphisms of MTHFR C677T, VDR C352T, and MPO G463A with risk for esophageal squamous cell dysplasia and carcinoma. Arch Med Res 39(6):594–600

    Article  PubMed  CAS  Google Scholar 

  58. Umar M, Upadhyay R, Khurana R et al (2010) Evaluation of MTHFR 677C > T polymorphism in prediction and prognosis of esophageal squamous cell carcinoma: a case-control study in a northern Indian population. Nutr Cancer 62(6):743–749

    Article  PubMed  CAS  Google Scholar 

  59. Lu C, Xie H, Wang F et al (2011) Diet folate, DNA methylation and genetic polymorphisms of MTHFR C677T in association with the prognosis of esophageal squamous cell carcinoma. BMC Cancer 11:91

    Article  PubMed  CAS  Google Scholar 

  60. Zeybek U, Yaylim I, Yilmaz H et al (2007) Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer. Cell Biochem Funct 25(4):419–422

    Article  PubMed  CAS  Google Scholar 

  61. Boccia S, Gianfagna F, Persiani R et al (2007) Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population. Biomarkers 12(6):635–644

    Article  PubMed  CAS  Google Scholar 

  62. Li S, Ji M, He N et al (2007) Application of microarray-based method for methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the risk of gastric carcinoma in east China population. J Nanosci Nanotechnol 7(9):3245–3249

    Article  PubMed  CAS  Google Scholar 

  63. Mu LN, Cao W, Zhang ZF et al (2007) Polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer. Biomarkers 12(1):61–75

    Article  PubMed  CAS  Google Scholar 

  64. Zhang FF, Terry MB, Hou L et al (2007) Genetic polymorphisms in folate metabolism and the risk of stomach cancer. Cancer Epidemiol Biomarkers Prev 16(1):115–121

    Article  PubMed  CAS  Google Scholar 

  65. Neves Filho EH, Alves MK, Lima VP et al (2010) MTHFR C677T polymorphism and differential methylation status in gastric cancer: an association with Helicobacter pylori infection. Virchows Arch 457(6):627–633

    Article  PubMed  CAS  Google Scholar 

  66. Götze T, Röcken C, Röhl FW et al (2007) Gene polymorphisms of folate metabolizing enzymes and the risk of gastric cancer. Cancer Lett 251(2):228–236

    Article  PubMed  CAS  Google Scholar 

  67. Zúñiga-Noriega JR, Velazco-Campos Mdel R, Aguirre-Rodríguez A et al (2007) C677T polymorphism of the MTHFR gene and the risk of developing distal gastric cancer in a Mexican population. Rev Gastroenterol Mex 72(4):355–358

    PubMed  Google Scholar 

  68. DeRe V, Cannizzaro R, Canzonieri V et al (2010) MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer. Tumour Biol 31(1):23–32

    Article  CAS  Google Scholar 

  69. Lin D, Li H, Tan W et al (2007) Genetic polymorphisms in folate-metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development. Forum Nutr 60:140–145

    Article  PubMed  CAS  Google Scholar 

  70. Wang L, Ke Q, Chen W et al (2007) Polymorphisms of MTHFD, plasma homocysteine levels, and risk of gastric cancer in a high-risk Chinese population. Clin Cancer Res 13(8):2526–2532

    Article  PubMed  CAS  Google Scholar 

  71. Cui LH, Shin MH, Kweon SS et al (2010) Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population. BMC Cancer 10:236

    Article  PubMed  CAS  Google Scholar 

  72. Wang Y, Guo W, He Y et al (2007) Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China. Cancer Causes Control 18(2):143–152

    Article  PubMed  CAS  Google Scholar 

  73. Ko KH, Kim NK, Yim DJ et al (2006) Polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) and thymidylate synthase enhancer region (TSER) as a risk factor of cholangiocarcinoma in a Korean population. Anticancer Res 26(6B):4229–4233

    PubMed  CAS  Google Scholar 

  74. Graziano F, Kawakami K, Ruzzo A et al (2006) Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population. Int J Cancer 118(3):628–632

    Article  PubMed  CAS  Google Scholar 

  75. Lacasaña-Navarro M, Galván-Portillo M, Chen J et al (2006) Methylenetetrahydrofolate reductase 677C > T polymorphism and gastric cancer susceptibility in Mexico. Eur J Cancer 42(4):528–533

    Article  PubMed  CAS  Google Scholar 

  76. Promthet SS, Pientong C, Ekalaksananan T et al (2010) Risk factors for colon cancer in Northeastern Thailand: interaction of MTHFR codon 677 and 1298 genotypes with environmental factors. J Epidemiol 20(4):329–338

    Article  PubMed  Google Scholar 

  77. Haghighi MM, Radpour R, Mahmoudi T et al (2009) Associaiton between MTHFR polymorphism (C677T) with nonfamilial colorectal cancer. Oncol Res 18(2–3):57–63

    Article  PubMed  CAS  Google Scholar 

  78. Levine AJ, Figueiredo JC, Lee W et al (2010) Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry. Cancer Epidemiol Biomarkers Prev 19(1):89–100

    Article  PubMed  CAS  Google Scholar 

  79. El Awady MK, Karim AM, Hanna LS et al (2009) Methylenetetrahydrofolate reductase gene polymorphisms and the risk of colorectal carcinoma in a sample of Egyptian individuals. Cancer Biomark 5(6):233–240

    PubMed  Google Scholar 

  80. Osian G, Procopciuc L, Vlad L (2007) MTHFR polymorphisms as prognostic factors in sporadic colorectal cancer. J Gastrointestin Liver Dis 16(3):251–256

    PubMed  Google Scholar 

  81. Chang SC, Lin PC, Lin JK et al (2007) Role of MTHFR polymorphisms and folate levels in different phenotypes of sporadic colorectal cancers. Int J Colorectal Dis 22(5):483–489

    Article  PubMed  Google Scholar 

  82. Cao HX, Gao CM, Takezaki T et al (2008) Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer. Asian Pac J Cancer Prev 9(2):203–208

    PubMed  Google Scholar 

  83. Wang J, Gajalakshmi V, Jiang J et al (2006) 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population. Int J Cancer 118(4):991–997

    Article  PubMed  CAS  Google Scholar 

  84. Iacopetta B, Heyworth J, Girschik J et al (2009) The MTHFR C677T and DeltaDNMT3B C-149T polymorphisms confer different risks for right- and left-sided colorectal cancer. Int J Cancer 125(1):84–90

    Article  PubMed  CAS  Google Scholar 

  85. Komlosi V, Hitre E, Pap E et al (2010) SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer. BMC Cancer 10:525

    Article  PubMed  CAS  Google Scholar 

  86. Derwinger K, Wettergren Y, Odin E et al (2009) A study of the MTHFR gene polymorphism C677T in colorectal cancer. Clin Colorectal Cancer 8(1):43–48

    Article  PubMed  CAS  Google Scholar 

  87. Rodrigues JO, Galbiatti AL, Ruiz MT et al (2010) Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and risk of head and neck squamous cell carcinoma. Braz J Otorhinolaryngol 76(6):776–782

    Article  PubMed  Google Scholar 

  88. Fard-Esfahani P, Fard-Esfahani A, Saidi P et al (2011) An increased risk of differentiated thyroid carcinoma in Iran with the 677C → T homozygous polymorphism in the MTHFR Gene. Cancer Epidemiol 35(1):56–58

    Article  PubMed  CAS  Google Scholar 

  89. Supic G, Jovic N, Kozomara R et al (2011) Interaction between the MTHFR C677T polymorphism and alcohol-impact on oral cancer risk and multiple DNA methylation of tumor-related genes. J Dent Res 90(1):65–70

    Article  PubMed  CAS  Google Scholar 

  90. Solomon PR, Selvam GS, Shanmugam G (2008) Polymorphism in ADH and MTHFR genes in oral squamous cell carcinoma of Indians. Oral Dis 14(7):633–639

    Article  PubMed  CAS  Google Scholar 

  91. Suzuki T, Matsuo K, Hasegawa Y et al (2007) One-carbon metabolism-related gene polymorphisms and risk of head and neck squamous cell carcinoma: case-control study. Cancer Sci 98(9):1439–1446

    Article  PubMed  CAS  Google Scholar 

  92. Vairaktaris E, Yapijakis C, Kessler P et al (2006) Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer. J Cancer Res Clin Oncol 132(4):219–222

    Article  PubMed  CAS  Google Scholar 

  93. Sailasree R, Nalinakumari KR, Sebastian P et al (2011) Influence of methylenetetrahydrofolate reductase polymorphisms in oral cancer patients. J Oral Pathol Med 40(1):61–66

    Article  PubMed  CAS  Google Scholar 

  94. Tsai CW, Hsu CF, Tsai MH et al (2011) Methylenetetrahydrofolate reductase (MTHFR) genotype, smoking habit, metastasis and oral cancer in Taiwan. Anticancer Res 31(6):2395–2399

    PubMed  CAS  Google Scholar 

  95. Boccia S, Boffetta P, Brennan P et al (2009) Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer. Cancer Lett 273(1):55–61

    Article  PubMed  CAS  Google Scholar 

  96. Galbiatti AL, Ruiz MT, Rodrigues JO et al (2012) Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk. Mol Biol Rep 39(1):635–643

    Article  PubMed  CAS  Google Scholar 

  97. Cao Y, Miao XP, Huang MY et al (2010) Polymorphisms of methylenetetrahydrofolate reductase are associated with a high risk of nasopharyngeal carcinoma in a smoking population from southern China. Mol Carcinog 49(11):928–934

    Article  PubMed  CAS  Google Scholar 

  98. Ni X, Tai J, Ma LJ et al (2008) Association between genetic polymorphisms in methylenetetrahydrofolate reductase and risk of laryngeal squamous cell carcinoma. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 43(6):435–438

    PubMed  Google Scholar 

  99. Kruszyna Ł, Lianeri M, Rydzanicz M et al (2010) Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer. Mol Biol Rep 37(1):241–247

    Article  PubMed  CAS  Google Scholar 

  100. Siraj AK, Ibrahim M, Al-Rasheed M et al (2008) Polymorphisms of selected xenobiotic genes contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. BMC Med Genet 9:61

    Article  PubMed  CAS  Google Scholar 

  101. Liu CS, Tsai CW, Hsia TC et al (2009) Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients. Cancer Genomics Proteomics 6(6):325–329

    PubMed  CAS  Google Scholar 

  102. Arslan S, Karadayi S, Yildirim ME et al (2011) The association between methylenetetrahydrofolate reductase gene polymorphism and lung cancer risk. Mol Biol Rep 38(2):991–996

    Article  PubMed  CAS  Google Scholar 

  103. Liu H, Jin G, Wang H et al (2008) Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population. Lung Cancer 61(1):21–29

    Article  PubMed  CAS  Google Scholar 

  104. Suzuki T, Matsuo K, Hiraki A et al (2007) Impact of one-carbon metabolism-related gene polymorphisms on risk of lung cancer in Japan: a case control study. Carcinogenesis 28(8):1718–1725

    Article  PubMed  CAS  Google Scholar 

  105. Kiyohara C, Horiuchi T, Takayama K et al (2011) Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese Population. BMC Cancer 11:459

    Article  PubMed  CAS  Google Scholar 

  106. Matakidou A, El Galta R, Rudd MF et al (2007) Prognostic significance of folate metabolism polymorphisms for lung cancer. Br J Cancer 97(2):247–252

    Article  PubMed  CAS  Google Scholar 

  107. Hung RJ, Hashibe M, McKay J et al (2007) Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis 28(6):1334–1340

    Article  PubMed  CAS  Google Scholar 

  108. Cui LH, Shin MH, Kim HN et al (2011) Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population. BMC Med Genet 12:28

    Article  PubMed  CAS  Google Scholar 

  109. Gemignani F, Landi S, Szeszenia-Dabrowska N et al (2007) Development of lung cancer before the age of 50: the role of xenobiotic metabolizing genes. Carcinogenesis 28(6):1287–1293

    Article  PubMed  CAS  Google Scholar 

  110. Ruiz-Argüelles GJ, Coconi-Linares LN, Garcés-Eisele J et al (2007) Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico. Hematology 12(5):387–391

    Article  PubMed  CAS  Google Scholar 

  111. Giovannetti E, Ugrasena DG, Supriyadi E et al (2008) Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia. Leuk Res 32(1):19–24

    Article  PubMed  CAS  Google Scholar 

  112. Tong N, Fang Y, Li J et al (2010) Methylenetetrahydrofolate reductase polymorphisms, serum methylenetetrahydrofolatereductase levels, and risk of childhood acute lymphoblastic leukemia in a Chinese population. Cancer Sci 101(3):782–786

    Article  PubMed  CAS  Google Scholar 

  113. Pietrzyk JJ, Bik-Multanowski M, Balwierz W et al (2009) Additional genetic risk factor for death in children with acute lymphoblastic leukemia: a common polymorphism of the MTHFR gene. Pediatr Blood Cancer 52(3):364–368

    Article  PubMed  Google Scholar 

  114. Alcasabas P, Ravindranath Y, Goyette G et al (2008) 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children. Pediatr Blood Cancer 51(2):178–182

    Article  PubMed  Google Scholar 

  115. Kim HN, Kim YK, Lee IK et al (2009) Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies. Leuk Res 33(1):82–87

    Article  PubMed  CAS  Google Scholar 

  116. Imanishi H, Okamura N, Yagi M et al (2007) Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. J Hum Genet 52(2):166–171

    Article  PubMed  CAS  Google Scholar 

  117. Chen BA, Jiang N, Ji MJ et al (2006) A new method for 5,10-methylenetetrahydrofolate reductase single nucleotide polymorphisms genotyping used to study susceptibility of hematological malignancy. Zhongguo Shi Yan Xue Ye Xue Za Zhi 14(6):1069–1077

    PubMed  CAS  Google Scholar 

  118. Bolufer P, Barragan E, Collado M et al (2006) Influence of genetic polymorphisms on the risk of developing leukemia and on disease progression. Leuk Res 30(12):1471–1491

    Article  PubMed  CAS  Google Scholar 

  119. Robien K, Bigler J, Yasui Y et al (2006) Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenousleukemia. Biol Blood Marrow Transplant 12(9):973–980

    Article  PubMed  CAS  Google Scholar 

  120. Zanrasso CW, Hatagima A, Emerenciano M et al (2006) The role of methylenetetrahydrofolate reductase in acute lymphoblastic leukemia in a Brazilian mixed population. Leuk Res 30(4):477–481

    Article  CAS  Google Scholar 

  121. Reddy H, Jamil K (2006) Polymorphisms in the MTHFR gene and their possible association with susceptibility to childhood acute lymphocytic leukemia in an Indian population. Leuk Lymphoma 47(7):1333–1339

    Article  PubMed  CAS  Google Scholar 

  122. Koppen IJ, Hermans FJ, Kaspers GJ (2010) Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia. Br J Haematol 148(1):3–14

    Article  PubMed  CAS  Google Scholar 

  123. Krull KR, Brouwers P, Jain N et al (2008) Folate pathway genetic polymorphisms are related to attention disorders in childhood leukemia survivors. J Pediatr 152(1):101–105

    Article  PubMed  CAS  Google Scholar 

  124. Thomas P, Fenech M (2008) Methylenetetrahydrofolate reductase, common polymorphisms, and relation to disease. Vitam Horm 79:375–392

    Article  PubMed  CAS  Google Scholar 

  125. Zintzaras E, Koufakis T, Ziakas PD et al (2006) A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia. Eur J Epidemiol 21(7):501–510

    Article  PubMed  CAS  Google Scholar 

  126. Yang L, Liu L, Wang J et al (2011) Polymorphisms in folate-related genes: impact on risk of adult acute lymphoblastic leukemia rather than pediatric in Han Chinese. Leuk Lymphoma 52(9):1770–1776

    Article  PubMed  CAS  Google Scholar 

  127. Damnjanovic T, Milicevic R, Novkovic T et al (2010) Association between the methylenetetrahydrofolate reductase polymorphisms and risk of acute lymphoblastic leukemia in Serbian children. J Pediatr Hematol Oncol 32(4):148–150

    Article  CAS  Google Scholar 

  128. Tantawy AA, El-Bostany EA, Adly AA et al (2010) Methylene tetrahydrofolate reductase gene polymorphism in Egyptian children with acute lymphoblastic leukemia. Blood Coagul Fibrinolysis 21(1):28–34

    Article  PubMed  CAS  Google Scholar 

  129. Pereira TV, Rudnicki M, Pereira AC et al (2006) Do polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene affect the risk of childhood acute lymphoblastic leukemia? Eur J Epidemiol 21(12):885–886

    Article  PubMed  Google Scholar 

  130. Sood S, Das R, Trehan A et al (2010) Methylenetetrahydrofolate reductase gene polymorphisms: association with risk for pediatric acute lymphoblastic leukemia in north Indians. Leuk Lymphoma 51(5):928–932

    Article  PubMed  CAS  Google Scholar 

  131. de Jonge R, Tissing WJ, Hooijberg JH et al (2009) Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 113(10):2284–2289

    Article  PubMed  CAS  Google Scholar 

  132. Yan J, Yin M, Dreyer ZE et al (2012) A meta-analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children. Pediatr Blood Cancer 58(4):513–518

    Article  PubMed  Google Scholar 

  133. Benetatos L, Dasoula A, Hatzimichael E et al (2011) Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes: genetic and epigenetic interactions. Ann Hematol 90(9):1037–1045

    Article  PubMed  CAS  Google Scholar 

  134. Karathananis NV, Stiakaki E, Goulielmos GN et al (2011) The role of the methylenetetrahydrofolate reductase 677 and 1298 polymorphisms in Cretan children with acute lymphoblastic leukemia. Genet Test Mol Biomarkers 15(1–2):5–10

    Article  CAS  Google Scholar 

  135. Sadananda Adiga MN, Chandy S, Ramachandra N et al (2010) Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children. Indian J Cancer 47(1):40–45

    Article  PubMed  CAS  Google Scholar 

  136. Kamel AM, Moussa HS, Ebid GT et al (2007) Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia. J Egypt Natl Canc Inst 19(2):96–105

    PubMed  Google Scholar 

  137. Oh D, Kim NK, Jang MJ et al (2007) Association of the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) polymorphisms in Korean patients with adult acute lymphoblastic leukemia. Anticancer Res 27(5A):3419–3424

    PubMed  CAS  Google Scholar 

  138. Amorim MR, Zanrosso CW, Magalhaes IQ et al (2008) MTHFR 677C→T and 1298A→C polymorphisms in children with Down syndrome and acute myeloid leukemia in Brazil. Pediatr Hematol Oncol 25(8):744–750

    Article  PubMed  CAS  Google Scholar 

  139. Kim NK, Chong SY, Jang MJ et al (2006) Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia. Anticancer Res 26(4B):2879–2881

    PubMed  CAS  Google Scholar 

  140. Lv L, Wu C, Sun H et al (2010) Combined 677CC/1298AC genotypes of methylenetetrahydrofolate reductase (MTHFR) reduce susceptibility to precursor B lymphoblastic leukemia in a Chinese population. Eur J Haematol 84(6):506–512

    Article  PubMed  CAS  Google Scholar 

  141. Moon HW, Kim TY, Oh BR et al (2007) MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea. Leuk Res 31(9):1213–1217

    Article  PubMed  CAS  Google Scholar 

  142. Hur M, Park JY, Cho HC et al (2006) Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population. Clin Lab Haematol 28(3):154–159

    Article  PubMed  CAS  Google Scholar 

  143. Azhar MR, Rahimi Z, Vaisi-Raygani A et al (2012) Lack of associaiton between MTHFR C677T and A1298C polymorphisms and risk of childhood acute lymphoblastic leukemia in the Kurdish Population from Western Iran. Genet Test Mol Biomarkers 16(3):198–202

    Article  PubMed  CAS  Google Scholar 

  144. Lee KM, Lan Q, Kricker A et al (2007) One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia. Hum Genet 122(5):525–533

    Article  PubMed  CAS  Google Scholar 

  145. Seidemann K, Book M, Zimmermann M et al (2006) MTHFR 677 (C→T) polymorphism is not relevant for prognosis or therapy-associated toxicity in pediatric NHL: results from 484 patients of multicenter trial NHL-BFM 95. Ann Hematol 85(5):291–300

    Article  PubMed  CAS  Google Scholar 

  146. Kurzwelly D, Knop S, Guenther M et al (2010) Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population. J Neurooncol 100(2):187–192

    Article  PubMed  CAS  Google Scholar 

  147. Ismail SI, Ababneh NA, Khader Y et al (2009) Methylenetetrahydrofolate reductase genotype association with the risk of follicular lymphoma. Cancer Genet Cytogenet 195(2):120–124

    Article  PubMed  CAS  Google Scholar 

  148. Kim HN, Lee IK, Kim YK et al (2008) Association between folate-metabolizing pathway polymorphism and non-Hodgkin lymphoma. Br J Haematol 140(3):287–294

    Article  PubMed  CAS  Google Scholar 

  149. Kasperzyk JL, Chang ET, Birmann BM et al (2011) Nutrients and genetic variation involved in one-carbon metabolism and Hodgkin lymphoma risk: a population-based case-control study. Am J Epidemiol 174(7):816–827

    Article  PubMed  Google Scholar 

  150. da Costa DM, de Lima GP, Faria MH et al (2012) Polymorphisms of folate pathway enzymes (methylenetetrahydrofolate reductase and thymidylate synthase) and their relationship with thymidylate synthase expression in human astrocytic tumors. DNA Cell Biol 31(1):57–66

    Article  PubMed  CAS  Google Scholar 

  151. Bethke L, Webb E, Murray A et al (2008) Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma. Cancer Epidemiol Biomarkers Prev 17(5):1195–1202

    Article  PubMed  CAS  Google Scholar 

  152. Sirachainan N, Wongruangsri S, Kajanachumpol S et al (2008) Folate pathway genetic polymorphisms and susceptibility of central nervous system tumors in Thai children. Cancer Detect Prev 32(1):72–78

    Article  PubMed  CAS  Google Scholar 

  153. Kafadar AM, Yilmaz H, Kafadar D et al (2006) C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in meningiomas and high-grade gliomas. Anticancer Res 26(3B):2445–2449

    PubMed  CAS  Google Scholar 

  154. Shekari M, Sobti RC, Kordi Tamandani DM et al (2008) Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population. Arch Gynecol Obstet 278(6):517–524

    Article  PubMed  CAS  Google Scholar 

  155. Tong SY, Kim MK, Lee JK et al (2011) Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12. Cancer Causes Control 22(1):63–77

    Article  PubMed  Google Scholar 

  156. Kohaar I, Kumar J, Thakur N et al (2010) Homocysteine levels are associated with cervical cancer independent of methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms in Indian population. Biomarkers 15(1):61–68

    Article  PubMed  CAS  Google Scholar 

  157. Uvuz F, Kilic S, Yilmaz N et al (2009) Relationship between preterm labor and thrombophilic gene polymorphism: a prospective sequential cohort study. Gynecol Obstet Invest 68(4):234–238

    Article  PubMed  Google Scholar 

  158. Tong SY, Lee JM, Song ES et al (2010) The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women. Cancer Causes Control 21(1):23–30

    Article  PubMed  Google Scholar 

  159. Xu WH, Shrubsole MJ, Xiang YB et al (2007) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 16(2):281–287

    Article  PubMed  CAS  Google Scholar 

  160. Delgado-Enciso I, Martínez-Garza SG, Rojas-Martínez A et al (2006) The effect of MTHFR polymorphisms, pregnancy and first intercourse on cervical cancer in a population from the Northeastern Mexico. Rev Invest Clin 58(5):462–469

    PubMed  Google Scholar 

  161. Piyathilake CJ, Azrad M, Macaluso M et al (2007) Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status. Nutrition 23(3):229–235

    Article  PubMed  CAS  Google Scholar 

  162. Rao GG, Kurien A, Gossett D et al (2006) A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis. Gynecol Oncol 101(2):250–254

    Article  PubMed  CAS  Google Scholar 

  163. Nandan NK, Wajid S, Biswas S et al (2008) Allelic variations in 5,10-methylenetetrahydrofolate reductase gene and susceptibility to cervical cancer in Indian women. Drug Metab Lett 2(1):18–22

    Article  PubMed  CAS  Google Scholar 

  164. Johansson M, Van Guelpen B, Hultdin J et al (2007) The MTHFR 677C→T polymorphism and risk of prostate cancer: results from the CAPS study. Cancer Causes Control 18(10):1169–1174

    Article  PubMed  Google Scholar 

  165. Wu HC, Chang CH, Tsai RY et al (2010) Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in Taiwan. Anticancer Res 30(9):3573–3577

    PubMed  CAS  Google Scholar 

  166. Marchal C, Redondo M, Reyes-Engel A et al (2008) Association between polymorphisms of folate-metabolizing enzymes and risk of prostate cancer. Eur J Surg Oncol 34(7):805–810

    Article  PubMed  CAS  Google Scholar 

  167. Safarinejad MR, Shafiei N, Safarinejad S (2010) Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. Prostate 70(15):1645–1657

    Article  PubMed  CAS  Google Scholar 

  168. Van Guelpen BR, Wirén SM, Bergh AR et al (2006) Polymorphisms of methylenetetrahydrofolate reductase and the risk of prostate cancer: a nested case-control study. Eur J Cancer Prev 15(1):46–50

    Article  PubMed  Google Scholar 

  169. Cai DW, Liu XF, Bu RG et al (2009) Genetic polymorphisms of MTHFR and aberrant promoter hypermethylation of the RASSF1A gene in bladder cancer risk in a Chinese population. J Int Med Res 37(6):1882–1889

    PubMed  CAS  Google Scholar 

  170. Muslumanoglu MH, Tepeli E, Demir S et al (2009) The analysis of the relationship between A1298C and C677T polymorphisms of the MTHFR gene with prostate cancer in Eskisehir population. Genet Test Mol Biomarkers 13(5):641–645

    Article  PubMed  CAS  Google Scholar 

  171. Chung CJ, Pu YS, Su CT et al (2010) Polymorphisms in one-carbon metabolism pathway genes, urinary arsenic profile, and urothelial carcinoma. Cancer Causes Control 21(10):1605–1613

    Article  PubMed  Google Scholar 

  172. Manuguerra M, Matullo G, Veglia F et al (2007) Multi-factor dimensionality reduction applied to a large prospective investigation on gene–gene and gene–environment interactions. Carsinogenesis 28(2):414–422

    Article  CAS  Google Scholar 

  173. Rouissi K, Ouerhani S, Oliveira E et al (2009) Polymorphisms in one-carbon metabolism pathway genes and risk for bladder cancer in a Tunusian population. Cancer Genet Cytogenet 195(1):43–45

    Article  PubMed  CAS  Google Scholar 

  174. Safarinejad MR, Shafiei N, Safarinejad S (2011) Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men. Med Oncol. doi:10.1007/s12032-010-9723-9

    PubMed  Google Scholar 

  175. Moore LE, Malats N, Rothman N et al (2007) Polymorphisms in one-carbon metabolism and trans-sulfuration pathway genes and susceptibility to bladder cancer. Int J Cancer 120(11):2452–2458

    Article  PubMed  CAS  Google Scholar 

  176. Sanyal S, Ryk C, De Verdier PJ et al (2007) Polymorphisms in NQO1 and the clinical course of urinary bladder neoplasms. Scand J Urol Nephrol 41(3):182–190

    Article  PubMed  CAS  Google Scholar 

  177. Izmirli M, Inandiklioglu N, Abat D et al (2011) Polymorphisms of MTHFR gene on bladder cancer in Turkish Population. Asian Pac J Cancer Prev 12(7):1833–1835

    PubMed  Google Scholar 

  178. Safarinejad MR, Shafiei N, Safarinejad S (2012) Methlenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C and G1793A polymorphisms: association with risk for clear cell renal cell carcinoma and tumour behaviour in men. Clin Oncol 24(4):269–281

    Article  CAS  Google Scholar 

  179. Sakano S, Hinoda Y, Okayama N et al (2010) Gender-specific association of methylenetetrahydrofolate reductase genotype and haplotype with the aggressiveness and prognosis of clear cell renal cell carcinoma in Japanese patients. BJU Int 106(3):424–430

    Article  PubMed  CAS  Google Scholar 

  180. Ferrara M, Capozzi L, Russo R (2009) Impact of the MTHFR C677T polymorphism on risk of Wilms tumor: case-control study. J Pediatr Hematol Oncol 31(4):256–258

    Article  PubMed  CAS  Google Scholar 

  181. Moore LE, Hung R, Karami S et al (2008) Folate metabolism genes, vegetable intake and renal cancer risk in central Europe. Int J Cancer 122(8):1710–1715

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

For his contribution to my education, I want to acknowledge and thank Prof. Dr. Davut Alptekin of Cukuruva University, Medical School and Department of Medical Biology.

Author information

Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, 34093, Istanbul, Turkey

    Muzeyyen Izmirli

Authors
  1. Muzeyyen Izmirli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muzeyyen Izmirli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Izmirli, M. A literature review of MTHFR (C677T and A1298C polymorphisms) and cancer risk. Mol Biol Rep 40, 625–637 (2013). https://doi.org/10.1007/s11033-012-2101-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2101-2

Keywords

Search

Navigation