The 677C>T (rs1801133) Polymorphism in the MTHFR Gene Contributes to Colorectal Cancer Risk: A Meta-Analysis Based on 71 Research Studies

PLoS ONE

Volumn 8, Issue 2, 2013, Pages

  Teng, Zan ^a   Wang, Lei ^a   Cai, Shuang ^a   Yu, Ping ^a   Wang, Jin ^a   Gong, Jing ^a   Liu, Yunpeng ^a  

^a CHINA MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2);

AFRICAN; ARTICLE; ASIAN; CANCER RISK; CANCER SUSCEPTIBILITY; CAUCASIAN; COLORECTAL CANCER; ETHNIC GROUP; ETHNICITY; GENETIC ASSOCIATION; GENOTYPE; HUMAN; MTHFR GENE; QUALITY CONTROL; SINGLE NUCLEOTIDE POLYMORPHISM;

COLORECTAL NEOPLASMS; CONFIDENCE INTERVALS; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); POLYMORPHISM, SINGLE NUCLEOTIDE; PUBLICATION BIAS; RISK FACTORS;

EID: 84874252043     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0055332     Document Type: Article

References (95)

1. Jemal A, Siegel R, Xu J, Ward E, (2010) Cancer statistics. CA Cancer J Clin 60: 277-300.
2. Jemal A, Bray F, (2011) Center MM, Ferlay J, Ward E (2011) Global cancer statistics. CA Cancer J Clin 61: 69-90.
3. Rozen R, (1997) Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemost 78(1): 523-526.
4. Ames BN, (2001) DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 475: 7-20.
5. Giovannucci E, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, (1995) Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 87: 265-273.
6. Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, et al. (1998) Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J. Nutr 128: 1204-1212.
7. Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, et al. (2002) A common mutation in the 5,10-methylenetetrahydrofo-late reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci USA 99(8): 5606-11.
8. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1): 111-113.
9. Deloughery TG, Evans A, Sadeghi A, McWilliams J, Henner WD, et al. (1996) Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease 94: 3074-3078.
10. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, et al. (2003) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Available: http://www.ohri.ca/programs/clinical epidemiology/oxford.htm. Accessed 2009 Sept 25.
11. Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ, (2009) Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer 100: 1385-92.
12. The Cochrane Collaborative Review Group on HIV Infection and AIDS. Editorial Policy: Inclusion and Appraisal of Experimental and Non-experimental (Obser-vational) Studies; 2009. Available: http://www.igh.org/Cochrane. Accessed 2009 Sept 29.
13. Woolf B, (1955) On estimating the relation between blood group and disease. Ann Hum Genet 19: 251-3.
14. Mantel N, Haenszel W, (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719-48.
15. DerSimonian R, Laird N, (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177-88.
16. Cochran WG, (1954) The combination of estimates from different experiments. Biometrics 10: 101-129.
17. Higgins JP, Thompson SG, Deeks JJ, Altman DG, (2003) Measuring inconsistency in meta-analyses. BMJ 327: 557-560.
18. Egger M, Smith DG, Schneider M, Minder C, (1997) Bias in meta analysis detected by a simple, graphical test. BMJ 315: 629-634.
19. Chen J, Giovannucci E, Kelsey K, Rimm EB, Stampfer MJ, et al. (1996) A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56(21): 4862-4864.
20. Ma J, Stampfer MJ, Giovannucci E, Artigas C, Hunter DJ, et al. (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 57(6): 1098-1102.
21. Park KS, Mok JW, Kim JC, (1999) The 677C>T mutation in 5, 10-methylenetetrahydrofolate reductase and colorectal cancer risk. Genet Test 3: 233-236.
22. Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M, (1999) Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 8(6): 513-518.
23. Slattery ML, Edwards SL, Samowitz W, Potter J, (2000) Associations between family history of cancer and genes coding for metabolizing enzymes (United States). Cancer Causes Control 11: 799-803.
24. Ryan BM, Molloy AM, McManus R, Arfin Q, Kelleher D, et al. (2001) The methylenetetrahydrofolate reductase (MTHFR) gene in colorectal cancer: role in tumor development and significance of allelic loss in tumor progression. Int J Gastrointest Cancer 30(3): 105-111.
25. Keku T, Millikan R, Worley K, Winkel S, Eaton A, et al. (2002) 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites. Cancer Epidemiol Biomarkers Prev 11(12): 1611-1621.
26. Le Marchand L, Donlon T, Hankin JH, Kolonel LN, Wilkens LR, et al. (2002) B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes Control 13(3): 239-248.
27. Matsuo K, Hamajima N, Hirai T, Kato T, Inoue M, et al. (2002) Methionine synthase reductase gene A66G polymorphism is associated with risk of colorectal cancer. Asian Pac J Cancer Prev 3: 353-359.
28. Sachse C, Smith G, Wilkie MJ, Barrett JH, Waxman R, et al. (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23(11): 1839-1849.
29. Shannon B, Gnanasampanthan S, Beilby J, Iacopetta B, (2002) A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability. Gut 50(4): 520-524.
30. Toffoli G, Gafà R, Russo A, Lanza G, Dolcetti R, et al. (2003) Methylenetetrahydrofolate reductase 677C→T polymorphism and risk of proximal colon cancer in north Italy. Clinical cancer research 9(2): 743-748.
31. Heijmans BT, Boer J, Suchiman HED, Cornelisse CJ, Westendorp RGJ, et al. (2003) A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer research 63(6): 1249.
32. Plaschke J, Schwanebeck U, Pistorius S, Saeger HD, Schackert HK, (2003) Methylenetetrahydrofolate reductase polymorphisms and risk of sporadic and hereditary colorectal cancer with or without microsatellite instability. Cancer Lett 191(2): 179-185.
33. Pufulete M, Al-Ghnaniem R, Leather AJ, Appleby P, Gout S, et al. (2003) Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study. Gastroenterology 124(5): 1240-1248.
34. Kim DH, Ahn YO, Lee BH, Tsuji E, Kiyohara C, et al. (2004) Methylenetetrahydrofolate reductase polymorphism, alcohol intake, and risks of colon and rectal cancers in Korea. Cancer Lett, 216: 199-205.
35. Huang P, Zhou ZY, Ma HT (2003) MTHFR polymorphisms and colorectal cancer susceptibility in Chongging people. Acta Academiae Med Militaris Tertiae, 25: 1710-1715.
36. Yin G, Kono S, Toyomura K, Hagiwara T, Nagano J, et al. (2004) Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer, the Fukuoka Colorectal Cancer Study. Cancer Sci 95: 908-913.
37. Ulvik A, Vollset SE, Hansen S, Gislefoss R, Jellum E, et al. (2004) Colorectal cancer and the methylenetetrahydrofolate reductase 677C>T and methionine synthase 2756A>G polymorphisms: a study of 2,168 case-control pairs from the JANUS cohort. Cancer Epidemiol Biomarkers Prev 13(12): 2175-2180.
38. Curtin K, Bigler J, Slattery ML, Caan B, Potter JD, et al. (2004) MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 13: 285-292.
39. Otani T, Iwasaki M, Hanaoka T, Kobayashi M, Ishihara J, et al. (2005) Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan. Nutr Cancer 53(1): 42-50.
40. Jiang Q, Chen K, Ma X, Li Q, Yu W, et al. (2005) Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer. Cancer Detect Prev 29: 146-154.
41. Matsuo K, Ito H, Wakai K, Hirose K, Saito T, et al. (2005) One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan. Carcinogenesis 26: 2164-2171.
42. Le Marchand L, Wilkens LR, Kolonel LN, Henderson BE, (2005) The MTHFR C677T polymorphism and colorectal cancer: the multiethnic cohort study. Cancer Epidemiology Biomarkers & Prevention 14(5): 1198-1203.
43. Miao XP, Yang S, Tan W, Zhang XM, Ye YJ, et al. (2005) Association between genetic variations in methylenetetrahydrofolate reductase and risk of colorectal cancer in a Chinese population. Zhonghua Yu Fang Yi Xue Za Zhi 39: 409-411.
44. Landi S, Gemignani F, Moreno V, Gioia-Patricola L, Chabrier A, et al. (2005) A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer. Pharmacogenet Genomics 15: 535-546.
45. Wang J, Gajalakshmi V, Jiang J, Kuriki K, Suzuki S, et al. (2006) Associations between 5,10-methylenetetrahy-drofolate 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: 991-997.
46. Koushik A, Kraft P, Fuchs CS, Hankinson SE, Willett WC, et al. (2006) Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer. Cancer Epidemiol Biomarkers Prev 15(12): 2408-2417.
47. Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Stenling R, et al. (2006) Low folate levels may protect against colorectal cancer. Gut 55(10): 1461-1466.
48. Battistelli S, Vittoria A, Stefanoni M, Bing C, Roviello F, (2006) Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma. World J Gastroenterol 12: 6128-6132.
49. Murtaugh MA, Curtin K, Sweeney C, Wolff RK, Holubkov R, et al. (2007) Dietary intake of folate and co-factors in folate metabolism, MTHFR polymorphisms, and reduced rectal cancer. Cancer Causes Control 18: 153-163.
50. Chang SC, Lin PC, Lin JK, Yang SH, Wang HS, et al. (2007) Role of MTHFR polymorphisms and folate levels in different phenotypes of sporadic colorectal cancers. Int J Colorectal Dis 22: 483-489.
51. Jin XX, Zhu ZZ, Wang AZ, Hangruo Jia, (2007) Association of methylenetetrahydrofoIate reductase C677T polymorphism with genetic susceptibility to colorectal cancer. Shijie Huaren Xiao Hua Za Zhi 15: 2754-2757.
52. Zeybek U, Yaylim I, Yilmaz H, Agachan B, Ergen A, et al. (2007) Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer. Cell Biochem Funct 25(4): 419-422.
53. Osian G, Procopciuc L, Vlad L, (2007) MTHFR polymorphisms as prognostic factors in sporadic colorectal cancer. J Gastrointest Liver Dis 16: 251-256.
54. Lima CS, Nascimento H, Bonadia LC, Teori MT, Coy CS, et al. (2007) Polymorphisms in methylenetetrahydrofolate reductase gene (MTHFR) and the age of onset of sporadic colorectal adenocarcinoma. Int J Colorectal Dis 22(7): 757-63.
55. Theodoratou E, Farrington SM, Tenesa A, McNeill G, Cetnarskyj R, et al. (2008) Dietary vitamin B6 intake and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 17(1): 171-182.
56. Cao HX, Gao CM, Takezaki T, Wu JZ, Ding JH, et al. (2008) Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer. Asian Pac J Cancer Prev 9: 203-208.
57. Zhang YL, Yuan XY, Zhang C, Yang Y, Pan YM, et al. (2008) Relationship between polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase and susceptibility in Liaoning Benxi colorectal cancer pafients. Linchuang Zhong Liu Xue Za Zhi 13: 769-774.
58. Mohebbi SR, Khatami F, Ghiasi S, Derakhshan F, Atarian H, et al. (2008) Reverse association between MTHFR polymorphism (C677T) with sporadic colorectal cancer. Gastroenterology and Hepatology from bed to bench 1(2): 57-63.
59. Sharp L, Little J, Brockton NT, Cotton SC, Masson LF, et al. (2008) Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake. Br J Nutr 99(2): 379-389.
60. Eklof V, Van Guelpen B, Hultdin J, Johansson I, Hallmans G, et al. (2008) The reduced folate carrier (RFC1) 80G [A and folate hydrolase 1 (FOLH1) 1561C [T polymorphisms and the risk of colorectal cancer: a nested case-referent study. Scand J Clin Lab Invest 68: 393-401.
61. Kury S, Buecher B, Robiou-du-Pont S, Scoul C, Colman H, et al. (2008) Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study. BMC Cancer 8: 326.
62. Mokarram P, Naghibalhossaini F, Saberi Firoozi M, Hosseini SV, Izadpanah A, et al. (2008) Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status. World J Gastroenterol 14: 3662-3671.
63. Fernandez-Peralta AM, Daimiel L, Nejda N, Iglesias D, Medina Arana V, et al. (2010) Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy. Int J Colorectal Dis 25(2): 141-151.
64. Derwinger K, Wettergren Y, Odin E, Carlsson G, Gustavsson B, (2009) A study of the MTHFR gene polymorphism C677T in colorectal cancer. Clin Colorectal Cancer 8: 43-48.
65. Iacopetta B, Heyworth J, Girschik J, Grieu F, Clayforth C, 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: 84-90.
66. El Awady MK, Karim AM, Hanna LS, El Husseiny LA, El Sahar M, et al. (2009) Methylenetetrahydrofolate reductase gene polymorphisms and the risk of colorectal carcinoma in a sample of Egyptian individuals. Cancer Biomark 5(6): 233-40.
67. de Vogel S, Wouters KA, Gottschalk RW, van Schooten FJ, de Goeij AF, et al. (2009) Genetic variants of methyl metabolizing enzymes and epigenetic regulators: associations with promoter CpG island hypermethylation in colorectal cancer. Cancer Epidemiol Biomarkers Prev 18: 3086-3096.
68. Gallegos-Arreola MP, Garcia-Ortiz JE, Figuera LE, Puebla-Perez AM, Morgan-Villela G, et al. (2009) Association of the 677C>T polymorphism in the MTHFR gene with colorectal cancer in Mexican patients. Cancer Genomics Proteomics 6: 183-188.
69. Reeves SG, Meldrum C, Groombridge C, Spigelman AD, Suchy J, et al. (2009) MTHFR 677 C>T and 1298 A>C polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer. Eur J Hum Genet 17: 629-635.
70. Cui LH, Shin MH, Kweon SS, Kim HN, Song HR, et al. (2010) Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population. BMC Cancer 10: 236.
71. Promthet SS, Pientong C, Ekalaksananan T, Wiangnon S, Poomphakwaen K, 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: 329-338.
72. Yang XX, Li FX, Yi JP, Bai J, Fu S, (2010) Association of MTHFR C677T polymorphism and susceptibility of lung cancer, gastric cancer and colorectal cancer risk. Guangdong Yi Xue 31: 2375-2378.
73. Zhu F, Wang YM, Zhang QM, (2010) A case-control study of plasma homocysteine, serum folate, the polymorphism of methylenetetrahydrofolate reductase in colorectai cancer. Dongnan Da Xue Xue Bao 29: 88-92.
74. Guimaraes JL, Ayrizono Mde L, Coy CS, Lima CS, (2011) Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma. Tumour Biol 32(5): 853-861.
75. Komlosi V, Hitre E, Pap E, Adleff V, Reti A, et al. (2010) SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer. BMC Cancer 10: 525.
76. Naghibalhossaini F, Mokarram P, Khalili I, Vasei M, Hosseini SV, et al. (2010) MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients. Cancer Genet Cytogenet 197: 142-151.
77. Chandy S, Sadananda Adiga MN, Ramachandra N, Krishnamoorthy S, Ramaswamy G, et al. (2010) Association of methylenetetrahydrofolate reductase gene polymorphisms colorectal cancer in India. Indian J Med Res 131: 659-664.
78. Karpinski P, Myszka A, Ramsey D, Misiak B, Gil J, et al. (2010) Polymorphisms in methyl-group metabolism genes and risk of sporadic colorectal cancer with relation to the CpG island methylator phenotype. Cancer Epidemiol 34: 338-344.
79. Jokic M, Brcic-Kostic K, Stefulj J, Catela Ivkovic T, Bozo L, et al. (2011) Association of MTHFR, MTR, MTRR, RFC1, and DHFR gene polymorphisms with susceptibility to sporadic colon cancer. DNA Cell Biol 30(10): 771-776.
80. Pardini B, Kumar R, Naccarati A, Prasad RB, Forsti A, et al. (2011) MTHFR and MTRR genotype and haplotype analysis and colorectal cancer susceptibility in a case-control study from the Czech Republic. Mutat Res 721(1): 74-80.
81. Sameer AS, Shah ZA, Nissar S, Mudassar S, Siddiqi MA, (2011) Risk of colorectal cancer associated with the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in the Kashmiri population. Genet Mol Res 10(2): 1200-1210.
82. Zhu Q, Jin Z, Yuan Y, Lu Q, Ge D, et al. (2011) Impact of MTHFR gene C677T polymorphism on Bcl-2 gene methylation and protein expression in colorectal cancer. Scand J Gastroenterol 46: 436-445.
83. Kim JW, Park HM, Choi YK, Chong SY, Oh D, et al. (2011) Polymorphisms in genes involved in folate metabolism and plasma DNA methylation in colorectal cancer patients. Oncol Rep 25: 167-172.
84. Kang BS, Ahn DH, Kim NK, Kim JW, (2011) Relationship between metabolic syndrome and MTHFR polymorphism in colorectal cancer. J Korean Soc Coloproctol 27: 78-82.
85. Vossen CY, Hoffmeister M, Chang-Claude JC, Rosendaal FR, Brenner H, (2011) Clotting factor gene polymorphisms and colorectal cancer risk. J Clin Oncol 29: 1722-1727.
86. 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: 422-426.
87. Eussen SJ, Vollset SE, Igland J, Meyer K, Fredriksen A, et al. (2010) Plasma folate, related genetic variants, and colorectal cancer risk in EPIC. Cancer Epidemiol Biomarkers Prev 19: 1328-1340.
88. Mantel N, Haenszel W, (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719-748.
89. Yin G, Ming H, Zheng X, Xuan Y, Liang J, et al. (2012) Methylenetetrahydrofolate reductase C677T gene polymorphism and colorectal cancer risk: A case-control study. Oncol Lett 4(2): 365-369.
90. Skoog T, van't Hooft FM, Kallin B, Jovinge S, Boquist S, et al. (1999) A common functional polymorphism (C3A substitution at position-863) in the promoter region of the tumor necrosis factor (TNF-) gene associated with reduced circulating levels of TNF-. Hum. Mol Genet 8: 1443-1449.
91. Momparler RL, Bovenzi V, (2000) DNA methylation and cancer. J Cell Physiol 183: 145-154.
92. Shen H, Wang L, Spitz MR, Hong WK, Mao L, et al. (2002) A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res 62: 4992-4995.
93. Skoog T, van't Hooft FM, Kallin B, Jovinge S, Boquist S, et al. (1999) A common functional polymorphism (C>A substitution at position-863) in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet 8: 1443-1449.
94. Taioli E, Garza M, Ahn Y, Bishop D, Bost J, et al. (2009) Meta-and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. American journal of epidemiology 170(10): 1207-1221.
95. Yang Z, Zhang XF, Liu HX, Hao YS, Zhao CL, (2012) MTHFR C677T polymorphism and colorectal cancer risk in Asians, a meta-analysis of 21 studies. Asian Pac J Cancer Prev 13(4): 1203-1208.