MTHFR 677C>T polymorphism and the risk of breast cancer: Evidence from an original study and pooled data for 28031 cases and 31880 controls

PLoS ONE

Volumn 10, Issue 3, 2015, Pages

  Singh, Pooja ^a,b   Carlus, Justin ^c,d   Sekhar, Deepa ^a   Francis, Amirtharaj ^d   Gupta, Nishi ^a   Konwar, Rituraj ^a   Kumar, Sandeep ^e   Kumar, Surender ^b   Thangaraj, Kumarasamy ^d   Singh, Rajender ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

^b KING GEORGE'S MEDICAL UNIVERSITY   (India)

^c TAIBAH UNIVERSITY   (Saudi Arabia)

^d CENTRE FOR CELLULAR AND MOLECULAR BIOLOGY   (India)

^e ALL INDIA INSTITUTE OF MEDICAL SCIENCES   (India)

Author keywords

[No Author keywords available]

Indexed keywords

5 METHYLTETRAHYDROFOLIC ACID; 5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); CYTOSINE; HOMOCYSTEINE; METHIONINE; METHYLENETETRAHYDROFOLIC ACID; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2);

ADULT; AGED; ARTICLE; BREAST CANCER; CANCER RISK; CHI SQUARE TEST; CONSENSUS; CONTROLLED STUDY; CORRELATION ANALYSIS; DNA SYNTHESIS; DRAVIDIAN PEOPLE; FEMALE; GENOTYPE; HUMAN; INDIA; INDO-EUROPEAN PEOPLE; MAJOR CLINICAL STUDY; META ANALYSIS (TOPIC); NUCLEIC ACID BASE SUBSTITUTION; SINGLE NUCLEOTIDE POLYMORPHISM; STATISTICAL MODEL; ASIAN CONTINENTAL ANCESTRY GROUP; BREAST; BREAST NEOPLASMS; GENETICS; META ANALYSIS; METABOLISM; MIDDLE AGED; PATHOLOGY; RISK; VERY ELDERLY; YOUNG ADULT;

ADULT; AGED; AGED, 80 AND OVER; ASIAN CONTINENTAL ANCESTRY GROUP; BREAST; BREAST NEOPLASMS; FEMALE; HUMANS; INDIA; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK; YOUNG ADULT;

EID: 84925797448     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0120654     Document Type: Article

References (86)

1. Sangrajrang S, Sato S, Sakamoto H, Ohnami S, Khuhaprema T, Yoshida T. Genetic polymorphism in folate and alcohol metabolism and breast cancer risk: a case- control study in Thai women. Breast Cancer Res Treat. 2010; 123: 885-893. doi: 10.1007/s10549-010-0804-4 PMID: 20180013
2. Yu L, Chen J. Association of MHTFR Ala222Val (rs1801133) polymorphism and breast cancer susceptibility: An update meta-analysis based on 51 research studies. Diagn Pathol. 2012; 7: 171. doi: 10. 1186/1746-1596-7-171 PMID: 23217001
3. Shrubsole MJ, Gao YT, Cai O, Shu XO, Dai Q, Hebert JR, et al. MTHFR Polymorphisms, Dietary Folate Intake, and Breast Cancer Risk: Results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2004; 13:190-196. PMID: 14973091
4. Sharp L, Little J, Schofield AC, Pavlidou E, Cotton SC, Meidzybrodzka Z, et al. Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR).Cancer Lett. 2002; 181:65-71. PMID: 12430180
5. Ericson U, Sonestedt E, Ivarsson M.I, Gullberg B, Carlson J, Olsson H, et al. Folate intake, methylenetetrahydrofolate reductase polymorphisms, and breast cancer risk in women from the Malmö Diet and Cancer cohort. Cancer Epidemiol Biomarkers Prev. 2009; 18:1101-1110. doi: 10.1158/1055-9965. EPI-08-0401 PMID: 19336565
6. Kotsopoulos J, Zhang WW, Zhang S, McCready D, Trudeau M, Zhang P, et al. Polymorphisms in folate metabolizing enzymes and transport proteins and the risk of breast cancer. Breast Cancer Res Treat. 2008; 112:585-593. doi: 10.1007/s10549-008-9895-6 PMID: 18204969
7. Chou YC, Wu MH, Yu JC, Lee MS, Yang T. Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan. Carcinogenesis. 2006; 27: 2295-2300. PMID: 16777985
8. Langevin SM, Lin D, Matsuo K, Gao CM, Takezaki T, Stolzenberg-Solomom RZ, et al. Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer. Toxicol Lett. 2009; 184:73-80. doi: 10.1016/j.toxlet.2008.09.003 PMID: 18840514
9. Lee SA, Kang D, Nishio H, Lee MJ, Kim DH, Han W, et al. Methylenetetrahydrofolate reductase polymorphism, diet, and breast cancer in Korean women. Exp Mol Med. 2004; 36:116-121. PMID: 15150439
10. Macis D, Maisonneuve P, Johansson H, Bonanni B, Botteri E, Iodice S, et al. Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis. Breast Cancer Res Treat. 2007; 106:263-271. PMID: 17260091
11. Hosseini M, Houshmand M, Ebrahimi A. MTHFR polymorphisms and breast cancer risk. Arch Med Sci. 2011; 7:134-137. doi: 10.5114/aoms.2011.20618 PMID: 22291746
12. Deligezer U, Akisik EE, Dalay N. Homozygosity at the C677T of the MTHFR gene is associated with increased breast cancer risk in the Turkish population. In Vivo. 2005; 19:889-893. PMID: 16097444
13. Le Marchand L, Haiman CA, Wilkens LR, Kolonel LN, Henderson BE. MTHFR polymorphisms, diet, HRT, and breast cancer risk: the multiethnic cohort study.Cancer Epidemiol Biomarkers Prev. 2004; 13:2071-2077. PMID: 15598763
14. Lewis SJ, Harbord RM, Harris R, Smith GD. Meta-analyses of Observational and Genetic Association Studies of Folate Intakes or Levels and Breast Cancer Risk. Journal of the National Cancer Institute. 2006; 98: 122.
15. Zintzaras E. Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a metaanalysis. Clin Genet. 2006; 69: 327-336. PMID: 16630166
16. Zhang J, Qiu LX, Wang ZH, Wu XH, Liu XJ. MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls. Breast Cancer Res Treat. 2010; 123: 549-555. doi: 10.1007/s10549-010-0783-5 PMID: 20143151
17. Qi X, Ma X, Yang X, Fan L, Zhang Y. Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta-analysis from 41 studies with 16,480 cases and 22,388 controls. Breast Cancer Res Treat. 2011; 123: 499-506.
18. Liang H, Yan Y, Li T, Li R, Li M, Li S, et al. Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk in Chinese population: a meta-analysis of 22 case-control studies. Tumour Biol. 2013; 35: 1695-1701.
19. Huedo-Medina TB, Sanchez-Meca J, Marin-Martinez F, Botella J. Assessing heterogeneity in Metaanalysis: Q statistic or I2 Index. Physcol Methods. 2006; 11: 193-206.
20. Petitti DB. Approaches to heterogeneity in meta-analysis. Stat Med. 2001; 20: 3625-3633. PMID: 11746342
21. Mohammad NS, Yedluri R, Addepalli P, Gottumukkala SR, Digumarti RR, Kutala VK. Aberrations in one-carbon metabolism induce oxidative DNA damage in sporadic breast cancer. Mol Cell Biochem. 2011; 349:159-167. doi: 10.1007/s11010-010-0670-8 PMID: 21113649
22. Bailey LB. Folate, methyl-related nutrients, alcohol, and the MTHFR 677C->T polymorphism affect cancer risk: intake recommendations. J Nutr. 2003; 133: 3748S-3753S. PMID: 14608109
23. Sohn KJ, Jang H, Campan M, Weisenberger DJ, Dickhout J, Wang YC, et al. The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification. Int J Cancer. 2009; 124:1999-2005. doi: 10.1002/ijc.24003 PMID: 19123462
24. Ferroni P, Palmirotta R, Martini F, Riondino S, Savonarola A, Spila A, et al. Determinants of homocysteine levels in colorectal and breast cancer patients. Anticancer Res. 2009; 29:4131-4138. PMID: 19846961
25. Eroʇlu A, Akar N. Factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms and the risk of tamoxifen-associated thromboembolism in breast cancer patients. Thromb Res. 2011; 127:384-385. doi: 10.1016/j.thromres.2010.10.025 PMID: 21093891
26. Tamura T, Kurata M, Kondo T, Goto Y, Kamiya Y, Kawai S, et al. Preventive medical services not covered by public health insurance at Daiko Medical Center in Japan, 2004-2011. Nagoya J Med Sci. 2012; 74:115-121. PMID: 22515117
27. Akilzhanova A, Nurkina Z, Momynaliev K, Ramanculov E, Zhumadilov Z. Genetic profile and determinants of homocysteine levels in Kazakhstan patients with breast cancer. Anticancer Res. 2013; 33: 4049-4059. PMID: 24023349
28. Iwasaki M, Mizusawa J, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, et al. Green Tea Consumption and Breast Cancer Risk in JapaneseWomen: A Case-Control Study. Nutr Cancer. 2014; 66: 57-67. doi: 10.1080/01635581.2014.847963 PMID: 24274352
29. Ozen F, Erdis E, Sik E, Silan F, Uludag A, Ozdemir O. Germ-line MTHFR C677T, FV H1299R and PAI-1 5G/4G variations in breast carcinoma. Asian Pac J Cancer Prev. 2013; 14:2903-2908. PMID: 23803051
30. Martin YN, Olson JE, Ingle JN, Vierkant RA, Fredericksen ZS. Methylenetetrahydrofolate reductase haplotype tag single-nucleotide polymorphisms and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2006; 15: 2322-2324. PMID: 17119067
31. Huang MY, Wang YH, Chen FM, Lee SC, Fang WY, Cheng TL, et al. 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. 2008; 15:872-880. PMID: 18095031
32. Tao MH, Shields PG, Nie J, Marian C, Ambrosone CB, McCann SE, et al. DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR. Cancer Epidemiol Biomarkers Prev. 2009; 18:998-1002. doi: 10.1158/1055-9965.EPI-08-0916 PMID: 19240236
33. Knechtel G, Hofmann G, Gerger A, Renner W, Langsenlehner T, Skandera J, et al. Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer. J Cancer Res Clin Oncol. 2010; 136:1813-1819. doi: 10.1007/s00432-010-0839-2 PMID: 20204402
34. Papandreou CN, Doxani C, Zdoukopoulos N, Vlachostergios PJ, Hatzidaki E, Bakolas G, et al. 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. 2012; 31:193-198. doi: 10.1089/dna.2011.1292 PMID: 21875371
35. Eroglu A, Karabiyik A, Akar N. The association of protease activated receptor 1 gene-506 I/D polymorphism with disease-free survival in breast cancer patients. Ann Surg Oncol. 2012; 19: 1365-1369. doi: 10.1245/s10434-011-1969-8 PMID: 21822552
36. Campbell IG, Baxter SW, Eccles DM, Choong DY. Methylenetetrahydrofolate reductase polymorphism and susceptibility to breast cancer. Breast Cancer Res. 2002; 4:R14. PMID: 12473175
37. Semenza JC, Delfino RJ, Ziogas A, Anton-Culver H. Breast cancer risk and methylenetetrahydrofolate reductase polymorphism. Breast Cancer Res Treat. 2003; 77:217-223. PMID: 12602921
38. Langsenlehner U, Krippl P, RennerW, Yazdani-Biuki B, Wolf G. The common 677C>T gene polymorphism of methylenetetrahydrofolate reductase gene is not associated with breast cancer risk. Breast Cancer Res Treat. 2003; 81: 169-172. PMID: 14572159
39. Ergul E, Sazci A, Utkan Z, Canturk NZ. Polymorphisms in the MTHFR gene are associated with breast cancer. Tumour Biol. 2003; 24: 286-290. PMID: 15004488
40. Forsti A, Angelini S, Festa F, Sanyal S, Zhang Z, Grzybowska E, et al. Single nucleotide polymorphisms in breast cancer. Oncol Rep. 2004; 11:917-922. PMID: 15010895
41. Grieu F, Powell B, Beilby J, Iacopetta B. Methylenetetrahydrofolate reductase and thymidylate synthase polymorphisms are not associated with breast cancer risk or phenotype. Anticancer Res. 2004; 24: 3215-3219. PMID: 15510613
42. Lin WY, Chou YC, Wu MH, Huang HB, Jeng YL. The MTHFR C677T polymorphism, estrogen exposure and breast cancer risk: a nested case-control study in Taiwan. Anticancer Res. 2004; 24: 3863-3868. PMID: 15736423
43. Qi J, Miao XP, Tan W, Yu CY, Liang G, Lu WF, Lin DX. Association between genetic polymorphisms in methylenetetrahydrofolate reductase and risk of breast cancer. Chin J Oncol. 2004; 26:287-289
44. Kalemi TG, Lambropoulos AF, Gueorguiev M, Chrisafi S, Papazisis KT. The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece. Cancer Lett. 2005; 222: 57-65. PMID: 15837541
45. Justenhoven C, Hamann U, Pierl CB, Rabstein S, Pesch B. One-carbon metabolism and breast cancer risk: no association of MTHFR, MTR, and TYMS polymorphisms in the GENICA study from Germany. Cancer Epidemiol Biomarkers Prev. 2005; 14:3015-3018. PMID: 16365030
46. Chen J, Gammon MD, Chan W, Palomeque C, Wetmur JG. One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer. Cancer Res. 2005; 65: 1606-1614. PMID: 15735051
47. Kalyankumar C, Jamil K. Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and Breast Cancer in South Indian Population. International Journal of Cancer Research. 2006; 2: 143-151.
48. Xu X, Gammon MD, Zhang H, Wetmur JG, Rao M. Polymorphisms of one-carbon-metabolizing genes and risk of breast cancer in a population-based study. Carcinogenesis. 2007; 28: 1504-1509. PMID: 17372271
49. Hekim N, Ergen A, Yaylim I, Yilmaz H, Zeybek U, Ozturk O, et al. No association between methylenetetrahydrofolate reductase C677T polymorphism and breast cancer. Cell Biochem Funct. 2007; 25:115-117. PMID: 16134079
50. Lissowska J, Gaudet MM, Brinton LA, Chanock SJ, Peplonska B. Genetic polymorphisms in the onecarbon metabolism pathway and breast cancer risk: a population-based case-control study and metaanalyses. Int J Cancer. 2007; 120: 2696-2703. PMID: 17311260
51. Yu CP, Wu MH, Chou YC, Yang T, You SL, Chen CJ, Sun CA. Breast cancer risk associated with multigenotypic polymorphisms in folate-metabolizing genes: a nested case-control study in Taiwan. Anticancer Res. 2007; 27:1727-1732. PMID: 17595805
52. Kan XX, Zou TN, Wu XY, Wang X. Association between MTHFR genotype polymorphism and breast cancer susceptibility in human population from Yunnan. Cancer Res Prev Treat. 2007; 34:716-718.
53. Stevens VL, McCullough ML, Pavluck AL, Talbot JT, Feigelson HS, Thun MJ, et al. Association of polymorphisms in one-carbon metabolism genes and postmenopausal breast cancer incidence. Cancer Epidemiol Biomarkers Prev. 2007; 16:1140-1147. PMID: 17548676
54. Reljic A, Simundic AM, Topic E, Nikolac N, Justinic D. The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cancer risk: the Croatian case-control study. Clin Biochem. 2007; 40: 981-985. PMID: 17573062
55. InoueM, Robien K,Wang R, Van Den Berg DJ, KohWP, et al. Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study. Carcinogenesis. 2008; 29:1967-1972. doi: 10.1093/carcin/bgn177 PMID: 18669903
56. Suzuki T, Matsuo K, Hirose K, Hiraki A, Kawase T, Watanabe M, et al. One-carbon metabolism- related gene polymorphisms and risk of breast cancer. Carcinogenesis. 2008; 2:356-362. doi: 10.1093/carcin/ bgm295 PMID: 18174236
57. Cheng CW, Yu JC, Huang CS, Shieh JC, Fu YP. Polymorphism of cytosolic serine hydroxymethyltransferase, estrogen and breast cancer risk among Chinese women in Taiwan. Breast Cancer Res Treat. 2008; 111: 145-155. PMID: 17896178
58. Langsenlehner T, Renner W, Yazdani-Biuki B, Langsenlehner U. Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis. Breast Cancer Res Treat. 2008; 107: 459-460. PMID: 17453338
59. Mir MM, Dar JA, Dar NA, Dar MS, Salam I. 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. 2008; 2: 3-14.
60. Gao CM, Tang JH, Cao HX, Ding JH, Wu JZ, Wang J et al. MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women. J Hum Genet. 2009; 54:414-418. doi: 10.1038/jhg.2009.57 PMID: 19557016
61. Ma E, Iwasaki M, Kobayashi M, Kasuga Y, Yokoyama S. 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. 2009; 61: 447-456. doi: 10.1080/01635580802610123 PMID: 19838916
62. Platek ME, Shields PG, Marian C, McCann SE, Bonner MR. Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2009; 18: 2453-2459. doi: 10. 1158/1055-9965.EPI-09-0159 PMID: 19706843
63. Henriquez-Hernandez LA, Murias-Rosales A, Hernandez Gonzalez A, Cabrera De Leon A, Diaz-Chico BN. Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a casecontrol study. Oncol Rep. 2009; 22: 1425-1433. PMID: 19885596
64. Cam R, Eroglu A, Egin Y, Akar N. Dihydrofolate reductase (DHRF) 19-bp intron-1 deletion and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in breast cancer. Breast Cancer Res Treat. 2009; 115: 431-432. doi: 10.1007/s10549-008-0054-x PMID: 18498051
65. Maruti SS, Ulrich CM, Jupe ER, White E. MTHFR C677T and postmenopausal breast cancer risk by intakes of one-carbon metabolism nutrients: a nested case-control study. Breast Cancer Res. 2009; 11: R9. doi: 10.1186/bcr2225 PMID: 19228416
66. Ma E, Iwasaki M, Junko I, Hamada GS, Nishimoto IN. Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women. BMC Cancer. 2009; 9: 122. doi: 10.1186/1471-2407-9-122 PMID: 19389261
67. Li WD, Chen SQ. Association of methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk. J Prac Med. 2009; 25:2031-2033.
68. Yuan H, Xu XY, Wang ZL. The relation between polymorphisms of methylenetetrahydrofolate reductase C677T and the risk of breast cancer. J MuDanJiang Med Univ. 2009; 30:2-4.
69. Jin ZZ, Lu Q, Ge DH, Zong M, Zhu QH. Effect of the methylenetetrahydrofolate reductase gene C677Tpolymorphism on C-erbB-2 methylation status and its association with cancer. Mol Med Rep. 2009; 2:283-289. doi: 10.3892/mmr-00000097 PMID: 21475826
70. Bentley AR, Raiszadeh F, Stover PJ, Hunter DJ, Hankinson SE. No association between cSHMT genotypes and the risk of breast cancer in the Nurses' Health Study. Eur J Clin Nutr. 2010; 64: 108-110. doi: 10.1038/ejcn.2009.104 PMID: 19707223
71. Vainer AS, Boiarskikh UA, Voronina EN, Selezneva IA, Sinkina TV. 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 (Mosk). 2010; 44: 816-823. PMID: 21090237
72. Naushad SM, Pavani A, Digumarti RR, Gottumukkala SR, Kutala VK. Epistatic interactions between loci of one-carbon metabolism modulate susceptibility to breast cancer. Mol Biol Rep. 2010; 38: 4893-4901. doi: 10.1007/s11033-010-0631-z PMID: 21161404
73. Alshatwi AA. Breast cancer risk, dietary intake, and methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms. Food Chem Toxicol. 2010; 48: 1881-1885. doi: 10.1016/j.fct.2010.04. 028 PMID: 20417243
74. Batschauer AP, Cruz NG, Oliveira VC, Coelho FF, Santos IR. HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women. Mol Cell Biochem. 2011; 357: 247-253. doi: 10. 1007/s11010-011-0895-1 PMID: 21625954
75. Prasad VV, Wilkhoo H. Association of the functional polymorphism C677T in the methylenetetrahydrofolate reductase gene with colorectal, thyroid, breast, ovarian, and cervical cancers. Onkologie. 2011; 34:422-426. doi: 10.1159/000331131 PMID: 21934341
76. Ziva Cerne J, Stegel V, Gersak K, Novakovic S. Lack of association between methylenetetrahydrofolate reductase genetic polymorphisms and postmenopausal breast cancer risk. Mol Med Rep. 2012; 4: 175-179.
77. 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: 1133-1139. doi: 10.1007/ s13277-012-0354-y PMID: 22373582
78. Carvalho Barbosa Rde C, Menezes DC, Freire TF, Sales DC, Alencar VH. Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent. Mol Biol Rep. 2012; 39: 4899-4907. doi: 10.1007/s11033-011-1285-1 PMID: 22134752
79. Jakubowska A, Rozkrut D, Antoniou A, Hamann U, Scott RJ, McGuffog L, 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; 106:2016-2024. doi: 10.1038/bjc. 2012.160 PMID: 22669161
80. 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; 13:1599-1603. PMID: 22799374
81. 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: 204-209. doi: 10. 4314/ahs.v12i2.20 PMID: 23056029
82. Wang ZG, Cui W, Yang LF, Zhu YQ, Wei WH. Association of dietary intake of folate and MTHFR genotype with breast cancer risk. Genet Mol Res. 2014; 13:5446-5451. doi: 10.4238/2014.July.24.24 PMID: 25078601
83. Weiwei Z, Liping C, Dequan L. Association between dietary intake of folate, vitamin B6, B12 & MTHFR, MTR Genotype and breast cancer risk. Pak J Med Sci. 2014; 30:106-1010. doi: 10.12669/pjms.301. 4189 PMID: 24639841
84. Huang CY, Chang WS, Shui HA, Hsieh YH, Loh CH, Wang HC, et al. Evaluation of the contribution of Methylenetetrahydrofolate Reductase genotypes to Taiwan Breast Cancer. Anticancer Res. 2014; 34:4109-4115. PMID: 25075036
85. Rai V. The Methylenetetrahydrofolate Reductase C677T Polymorphism and Breast Cancer Risk in Asian Populations. Asian Pac J Cancer Prev. 2014; 15:5853-5860. PMID: 25081713
86. Li K, Li W, Dong X. Association of 677 C>T (rs1801133) and 1298 A>C (rs1801131) polymorphisms in the MTHFR gene and breast cancer susceptibility: a meta-analysis based on 57 individual studies. PLoS One. 2014; 9:e71290. doi: 10.1371/journal.pone.0071290 PMID: 24945727