Supplementary reference
1. Liu Y, Zhou LS, Xu XM, Deng LQ, Xiao QK. Association of Dietary Intake of Folate, Vitamin B6 and B12
and MTHFR Genotype with Breast Cancer Risk. Asian Pac J Cancer Prev. 2013;14:5189–92.
2. Yousef AM, Shomaf M, Berger S, Ababneh N, Bobali Y, Ali D, Al-Hasan S, Diab O, Ismail S. Allele and
Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Colorectal Cancer
among Jordanian Population. Asian Pac J Cancer Prev. 2013;14:4559–65.
3. Akilzhanova A, Nurkina Z, Momynaliev K, Ramanculov E, Zhumadilov Z, Rakhypbekov T, Hayashida N,
Nakashima M, Takamura N. Genetic profile and determinants of homocysteine levels in Kazakhstan patients
with breast cancer. Anticancer Res. 2013;33:4049–59.
4. Vylliotis A, Yapijakis C, Nkenke E, Nisyrios T, Avgoustidis D, Adamopoulou M, Ragos V, Vassiliou S,
Koronellos N, Vairaktaris E. Effect of thrombosis-related gene polymorphisms upon oral cancer: a regression
analysis. Anticancer Res. 2013;33:4033–9.
5. Hosseini-Asl SS, Pourfarzi F, Barzegar A, Mazani M, Farahmand N, Niasti E, Yazdanbod A, Didevar R,
Akhavan H, Malekzadeh R. Decrease in gastric cancer susceptibility by MTHFR C677T polymorphism in
Ardabil Province, Iran. Turk J Gastroenterol. 2013;24:117–21.
6. Ashmore JH, Lesko SM, Muscat JE, Gallagher CJ, Berg AS, Miller PE, Hartman TJ, Lazarus P. Association
of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal
cancer in a population-based case–control study. Genes Chromosomes Cancer. 2013;52:945–53.
7. Qu HH, Cui LH, Wang K, Wang P, Song CH, Wang KJ, Zhang JY, Dai LP. The Methylenetetrahydrofolate
Reductase C677T Polymorphism Influences Risk of Esophageal Cancer in Chinese. Asian Pac J Cancer Prev.
2013;14:3163–8.
8. Ouerhani S1, Rouissi K, Marrakchi R, Ben Slama MR, Sfaxi M, Chebil M, ElGaaied AB. Combined effect of
NAT2, MTR nd MTHFR genotypes and tobacco on bladder cancer susceptibility in Tunisian population.
Cancer Detect Prev. 2009;32:395–402.
9. Heijmans BT1, Boer JM, Suchiman HE, Cornelisse CJ, Westendorp RG, Kromhout D, Feskens EJ, Slagboom
PE. A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased
risk of cancer. Cancer Res. 2003;63:1249–53.
10. de Vogel S, Meyer K, Fredriksen A, Ulvik A, Ueland PM, Nygård O, Vollset SE, Tell GS, Tretli S, Bjørge T.
Serum folate and vitamin B12 concentrations in relation to prostate cancer risk–a Norwegian
population-based nested case–control study of 3000 cases and 3000 controls within the JANUS cohort. Int J
Epidemiol. 2013;42:201–10.
11. da Costa DM, de Lima GP, Faria MH, Rabenhorst SH. Polymorphisms of folate pathway enzymes
(methylenetetrahydrofolate reductase and thymidylate synthase) and their relationship with thymidylate
synthase expression in human astrocytic tumors. DNA Cell Biol. 2012;31:57–66.
12. López-Cortés A1, Jaramillo-Koupermann G, Muñoz MJ, Cabrera A, Echeverría C, Rosales F, Vivar N,
Paz-y-Miño C. Genetic Polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G)
Genes Associated With Pathological Characteristics of Prostate Cancer in the Ecuadorian Population. Am J
Med Sci. 2013;346:447–54.
13. Fernández-Peralta AM, Daimiel L, Nejda N, Iglesias D, Medina Arana V, González-Aguilera JJ. 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. 2010;25:141–51.
14. Delgado-Plasencia L, Medina-Arana V, Bravo-Gutiérrez A, Pérez-Palma J, Álvarez-Argüelles H, Salido-Ruiz
E, Fernández-Peralta AM, González-Aguilera JJ. Impact of the MTHFR C677T polymorphism on colorectal
cancer in a population with low geneticvariability. Int J Colorectal Dis. 2013;28:1187–93.
15. Stevens VL, Rodriguez C, Sun J, Talbot JT, Thun MJ, Calle EE. No association of single nucleotide
polymorphisms in one-carbon metabolism genes with prostate cancer risk. Cancer Epidemiol Biomarkers
Prev, 2008;17:3612–4.
16. Silva RM, Fontes AC, Silva KA, Sant'Ana TA, Ramos FJ, Marques-Salles Tde J, Pombo-de-Oliveira MS,
Muniz MT. Polymorphisms involved in folate metabolism pathways and the risk of the development of
childhood acute leukemia. Genet Test Mol Biomarkers. 2013;17:147–52.
17. Collin SM1, Metcalfe C, Zuccolo L, Lewis SJ, Chen L, Cox A, Davis M, Lane JA, Donovan J, Smith GD,
Neal DE, Hamdy FC, Gudmundsson J, Sulem P, Rafnar T, Benediktsdottir KR, Eeles RA, Guy M, Kote-Jarai
Z; UK Genetic Prostate Cancer Study Group, Morrison J, Al Olama AA, Stefansson K, Easton DF, Martin
RM. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based
nested case–control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev.
2009;18:2528–39.
18. Li R, Wang R, Li Y, Li X, Feng Y, Li Y, Jiang C. Association study on MTHFR polymorphisms and
meningioma in northern China. Gene. 2013;516:291–3.
19. Fard-Esfahani P, Mohammadi Torbati P, Hashemi Z, Fayaz S, Golkar M. Analysis of relation between C677T
genotype in MTHFR gene and prostatic cancer in Iranian males. Acta Med Iran. 2012;50:657–63.
20. Ma J, Stampfer MJ, Giovannucci E, Artigas C, Hunter DJ, Fuchs C, Willett WC, Selhub J, Hennekens CH,
Rozen R. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal
cancer. Cancer Res. 1997;57:1098–102.
21. Saberi S, Zendehdel K, Jahangiri S, Talebkhan Y, Abdirad A, Mohajerani N, Bababeik M, Karami N, Esmaili
M, Oghalaie A, Hassanpour P, Amini N, Mohagheghi MA, Eshagh Hossieni M, Mohammadi M. Impact of
methylenetetrahydrofolate reductase C677T polymorphism on the risk of gastric cancer and its interaction
with Helicobacter pylori infection. Iran Biomed J. 2012;16:179–84.
22. Nasr AS, Sami RM, Ibrahim NY. Methylenetetrahydrofolate reductase gene polymorphisms (677C > T and
1298A > C) in Egyptian patients with non-Hodgkin lymphoma. J Cancer Res Ther. 2012;8:355–60.
23. de Cássia Carvalho Barbosa R, da Costa DM, Cordeiro DE, Vieira AP, Rabenhorst SH. Interaction of MTHFR
C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in
Northeast Brazil. Anticancer Res. 2012;32:4805–11.
24. Promthet S, Pientong C, Ekalaksananan T, Songserm N, Poomphakwaen K, Chopjitt P, Wiangnon S,
Tokudome S. Risk factors for rectal cancer and methylenetetrahydrofolate reductase polymorphisms in a
population in Northeast Thailand. Asian Pac J Cancer Prev. 2012;13:4017–23.
25. Ma J, Stampfer MJ, Christensen B, Giovannucci E, Hunter DJ, Chen J, Willett WC, Selhub J, Hennekens CH,
Gravel R, Rozen R. A polymorphism of the methionine synthase gene: association with plasma folate, vitamin
B12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 1999;8:825–9.
26. Diakite B, Tazzite A, Hamzi K, Jouhadi H, Nadifi S. Methylenetetrahydrofolate reductase C677T
polymorphism and breast cancer risk in Moroccan women. Afr Health Sci. 2012;12:204–9.
27. Mandal RK, Nissar K, Mittal RD. Genetic variants in metabolizing genes NQO1, NQO2, MTHFR and risk of
prostate cancer: a study from North India. Mol Biol Rep. 2012;39:11145–52.
28. Jiang N, Zhu X, Zhang H, Wang X, Zhou X, Gu J, Chen B, Ren J. The relationship between
methylenetetrahydrofolate reductase polymorphism and hematological malignancy. Clin Lab.
2014;60:767–74.
29. Cheng Z, Wang W, Dai LL, Kang Y. MTHFR C667T polymorphism association with lung cancer risk in
Henan province: a case–control study. Asian Pac J Cancer Prev. 2012;13:2491–4.
30. Kobayashi LC, Limburg H, Miao Q, Woolcott C, Bedard LL, Massey TE, Aronson KJ. Folate intake, alcohol
consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence
on prostate cancer risk and interactions. Front Oncol. 2012;2:100.
31. Couvert P, Carrié A, Tezenas du Montcel S, Vaysse J, Sutton A, Barget N, Trinchet JC, Beaugrand M, Ganne
N, Giral P, Chelly J. Insulin-like growth factor 2 gene methylation in peripheral blood mononuclear cells of
patients with hepatitis C related cirrhosis or hepatocellular carcinoma. Clin Res Hepatol Gastroenterol.
2012;36:345–51.
32. Wu XY, Ni J, Xu WJ, Zhou T, Wang X. Interactions between MTHFR C677T-A1298C variants and folic acid
deficiency affect breast cancer risk in a Chinese population. Asian Pac J Cancer Prev. 2012;13:2199–206.
33. Yin G, Ming H, Zheng X, Xuan Y, Liang J, Jin X. Methylenetetrahydrofolate reductase C677T gene
polymorphism and colorectal cancer risk: A case-control study. Oncol Lett. 2012;4:365–369.
34. Akram M, Malik FA, Kayani MA. Mutational analysis of the MTHFR gene in breast cancer patients of
Pakistani population. Asian Pac J Cancer Prev. 2012;13:1599–603.
35. Beebe-Dimmer JL, Iyer PT, Nriagu JO, Keele GR, Mehta S, Meliker JR, Lange EM, Schwartz AG, Zuhlke
KA, Schottenfeld D, Cooney KA. Genetic variation in glutathione S-transferase omega-1, arsenic
methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a
case–control study. Environ Health. 2012;11:43.
36. Amigou A, Rudant J, Orsi L, Goujon-Bellec S, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel
G, Haouy S, Chastagner P, Ducassou S, Rialland X, Hémon D, Clavel J. Folic acid supplementation, MTHFR
and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). Cancer Causes
Control. 2012;23:1265–77.
37. Jakubowska A, Rozkrut D, Antoniou A, Hamann U, et al. Association of PHB 1630 C>T and MTHFR 677
C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a
multicenter study. Br J Cancer. 2012;106:2016–24.
38. Orjuela MA1, Cabrera-Muñoz L, Paul L, Ramirez-Ortiz MA, Liu X, Chen J, Mejia-Rodriguez F,
Medina-Sanson A, Diaz-Carreño S, Suen IH, Selhub J, Ponce-Castañeda MV. Risk of retinoblastoma is
associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake.
Cancer. 2012;118:5912–9.
39. Zhang L, Liu W, Hao Q, Bao L, Wang K. Folate intake and methylenetetrahydrofolate reductase gene
polymorphisms as predictive and prognostic biomarkers for ovarian cancer risk. Int J Mol Sci.
2012;13:4009–20.
40. Lordelo GS, Miranda-Vilela AL, Akimoto AK, Alves PC, Hiragi CO, Nonino A, Daldegan MB,
Klautau-Guimarães MN, Grisolia CK. Association between methylene tetrahydrofolate reductase and
glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population.
Genet Mol Res. 2012;11:1013–26.
41. Ozdemir S, Silan F, Hasbek Z, Uludag A, Atik S, Erselcan T, Ozdemir O. Increased T-allele frequency of 677
C>T polymorphism in the methylenetetrahydrofolate reductase gene in differentiated thyroid carcinoma.
Genet Test Mol Biomarkers. 2012;16:780–4.
42. Gao S, Liu N, Ma Y, Ying L. Methylenetetrahydrofolate reductase gene polymorphisms as predictive and
prognostic biomarkers in ovarian cancer risk. Asian Pac J Cancer Prev. 2012;13:569–73.
43. Ragasudha PN, Thulaseedharan JV, Wesley R, Jayaprakash PG, Lalitha P, Pillai MR. A case–control
nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression. Nutr
Cancer. 2012;64:550–8.
44. Nikbakht M, MalekZadeh K, Kumar Jha A, Askari M, Marwaha RK, Kaul D, Kaur J. Polymorphisms of
MTHFR and MTR genes are not related to susceptibility to childhood ALL in North India. Exp Oncol.
2012;34:43–8.
45. Hussain SR, Naqvi H, Raza ST, Ahmed F, Babu SG, Kumar A, Zaidi ZH, Mahdi F. Methylenetetrahydrofolate
reductase C677T genetic polymorphisms and risk of leukaemia among the North Indian population. Cancer
Epidemiol. 2012;36:e227–31.
46. Arslan S, Karadayi S, Yildirim ME, Ozdemir O, Akkurt I. The association between
methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk. Mol Biol Rep.
2011;38:991–6.
47. Lajin B, Alhaj Sakur A, Ghabreau L, Alachkar A. Association of polymorphisms in one-carbon metabolizing
genes with breast cancer risk in Syrian women. Tumour Biol. 2012;33:1133–9.
48. Lee JE, Wei EK, Fuchs CS, Hunter DJ, Lee IM, Selhub J, Stampfer MJ, Willett WC, Ma J, Giovannucci E.
Cancer Causes Control. Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer
risk in three large nested case–control studies. 2012;23:537–45.
49. Küçükhüseyin Ö, Kurnaz Ö, Akadam-Teker AB, Narter F, Yılmaz-Aydoğan H, İsbir T. Effects of the MTHFR
C677T polymorphism on prostate specific antigen and prostate cancer. Asian Pac J Cancer Prev.
2011;12:2275–8.
50. Zhao P, Lin F, Li Z, Lin B, Lin J, Luo R. Folate intake, methylenetetrahydrofolate reductase polymorphisms,
and risk of esophageal cancer. Asian Pac J Cancer Prev. 2011;12:2019–23.
51. Hosseini M, Houshmand M, Ebrahimi A. MTHFR polymorphisms and breast cancer risk. Arch Med Sci.
2011;7:134–7.
52. Kim J, Cho YA, Kim DH, Lee BH, Hwang DY, Jeong J, Lee HJ, Matsuo K, Tajima K, Ahn YO. Dietary
intake of folate and alcohol, MTHFR C677T polymorphism, and colorectal cancer risk in Korea. Am J Clin
Nutr. 2012;95:405–12.
53. Matsuo K, Suzuki R, Hamajima N, Ogura M, Kagami Y, Taji H, Kondoh E, Maeda S, Asakura S, Kaba S,
Nakamura S, Seto M, Morishima Y, Tajima K. Association between polymorphisms of folate- and
methionine-metabolizing enzymes and susceptibility to malignant lymphoma. Blood. 2001;97:3205–9.
54. Huang GL, Wang SK, Su M, Wang TT, Cai HZ, Yin H, Sun GJ. Serum folate, MTHFR C677T polymorphism
and esophageal squamous cell carcinoma risk. Biomed Environ Sci. 2013;26:1008–12.
55. Pawlik P, Mostowska A, Lianeri M, Sajdak S, Kędzia H, Jagodzinski PP. Folate and choline metabolism gene
variants in relation to ovarian cancer risk in the Polish population. Mol Biol Rep. 2012;39:5553–60.
56. Carvalho Barbosa Rde C, Menezes DC, Freire TF, Sales DC, Alencar VH, Rabenhorst SH. Associations of
polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent.
Mol Biol Rep. 2012;39:4899–907.
57. Jakovljevic K, Malisic E, Cavic M, Radulovic S, Jankovic R. Association between methylenetetrahydrofolate
reductase polymorphism C677T and risk of chronic myeloid leukemia in Serbian population. Leuk
Lymphoma. 2012;53:1327–30.
58. Izmirli M, Inandiklioglu N, Abat D, Alptekin D, Demirhan O, Tansug Z, Bayazit Y. MTHFR gene
polymorphisms in bladder cancer in the Turkish population. Asian Pac J Cancer Prev. 2011;12:1833–5.
59. Ajaz S, Khaliq S, Hashmi A, Naqvi SA, Rizvi SA, Mehdi SQ. Polymorphisms in the methylene
tetrahydrofolate reductase gene and their unique combinations are associated with an increased susceptibility
to the renal cancers. Genet Test Mol Biomarkers. 2012;16:346–52.
60. Onur E, Kurdal AT, Tugrul B, Iskesen I, Dundar P, Taneli F, Ulman C, Var A. Is genetic screening necessary
for determining the possibility of venous thromboembolism in cancer patients? Med Princ Pract.
2012;21:160–3.
61. Galbiatti AL, da Silva LM, Ruiz-Cintra MT, Raposo LS, Maníglia JV, Pavarino EC, Goloni-Bertollo EM.
Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk.
Eur J Cancer. 2012;48:1525–31.
62. Kiyohara C, Horiuchi T, Takayama K, Nakanishi Y. Methylenetetrahydrofolate reductase polymorphisms and
interaction with smoking and alcohol consumption in lung cancer risk: a case–control study in a Japanese
population. BMC Cancer. 2011;11:459.
63. Azhar MR, Rahimi Z, Vaisi-Raygani A, Akramipour R, Madani H, Rahimi Z, Parsian A. Lack of association