Skip to main content

Advertisement

SpringerLink
Log in

The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case–control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case–control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19–1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63–3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47–2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12–1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Hennessy BT, Coleman RL, Markman M (2009) Ovarian cancer. Lancet 374:1371–1382

    Article  PubMed  CAS  Google Scholar 

  3. Bertone-Johnson ER (2005) Epidemiology of ovarian cancer: a status report. Lancet 365:101–102

    Article  PubMed  Google Scholar 

  4. Cannistra SA (2004) Cancer of the ovary. N Engl J Med 351:2519–2529

    Article  PubMed  CAS  Google Scholar 

  5. Pennington KP, Swisher EM (2012) Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol 124:347–353

    Article  PubMed  CAS  Google Scholar 

  6. Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130:129–132

    PubMed  CAS  Google Scholar 

  7. Larsson SC, Giovannucci E, Wolk A (2006) Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 131:1271–1283

    Article  PubMed  CAS  Google Scholar 

  8. Fodinger M, Horl WH, Sunder-Plassmann G (2000) Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol 13:20–33

    PubMed  CAS  Google Scholar 

  9. Frosst P, Blom HJ, Milos R et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111–113

    Article  PubMed  CAS  Google Scholar 

  10. Goyette P, Sumner JS, Milos R et al (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 7:195–200

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Terry KL, Tworoger SS, Goode EL et al (2010) MTHFR polymorphisms in relation to ovarian cancer risk. Gynecol Oncol 119:319–324

    Article  PubMed  CAS  Google Scholar 

  13. 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

    Article  PubMed  CAS  Google Scholar 

  14. Webb PM, Ibiebele TI, Hughes MC et al (2011) Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer. Eur J Clin Nutr 65:1133–1140

    Article  PubMed  CAS  Google Scholar 

  15. Gao S, Liu N, Ma Y et al (2012) Methylenetetrahydrofolate reductase gene polymorphisms as predictive and prognostic biomarkers in ovarian cancer risk. Asian Pac J Cancer Prev 13:569–573

    Article  PubMed  Google Scholar 

  16. Pawlik P, Mostowska A, Lianeri M et al (2012) Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population. Mol Biol Rep 39:5553–5560

    Article  PubMed  CAS  Google Scholar 

  17. Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  PubMed  CAS  Google Scholar 

  18. Asbridge M, Hayden JA, Cartwright JL (2012) Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. BMJ 344:e536

    Article  PubMed  Google Scholar 

  19. Millett GA, Flores SA, Marks G et al (2008) Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis. JAMA 300:1674–1684

    Article  PubMed  CAS  Google Scholar 

  20. Wells G, Shea B, O’connell D, et al. (2012) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses, Ottawa Health Research Institute Web site

  21. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  22. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  23. Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  24. Stuck AE, Rubenstein LZ, Wieland D (1998) Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ 316:469

    Article  PubMed  CAS  Google Scholar 

  25. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  26. Wu Y, Zhang JY, Zuo WJ (2007) Assoc iation between genetic polymorphisms of methylenetetrahydrofolate reductase C677T and susceptibility to ovarian cancer. Prog Obstet Gynecol 16:811–813

    Google Scholar 

  27. Jakubowska A, Rozkrut D, Antoniou A et al (2012) Association of PHB 1630C>T and MTHFR 677C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study. Br J Cancer 106:2016–2024

    Article  PubMed  CAS  Google Scholar 

  28. Song CX, Ping L, Ting W (2012) Folate, MTHFR C677T and A1298C polymorphisms with the relationship with ovarian cancer risk among Chinese females. Afr J Microbiol Res 6:4761–4766

    CAS  Google Scholar 

  29. Zhang L, Liu W, Hao Q et al (2012) Folate intake and methylenetetrahydrofolate reductase gene polymorphisms as predictive and prognostic biomarkers for ovarian cancer risk. Int J Mol Sci 13:4009–4020

    Article  PubMed  CAS  Google Scholar 

  30. Gershoni-Baruch R, Dagan E, Israeli D et al (2000) Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. Eur J Cancer 36:2313–2316

    Article  PubMed  CAS  Google Scholar 

  31. Kovalenko TF, Vaniusheva OV, Shilov IA et al (2006) Promoters of genes MTHFR from patients with hyperhomocysteinemia and PTEN from patients with malignant and benign endometrial and ovarian tumors. Bioorg Khim 32:414–423

    PubMed  CAS  Google Scholar 

  32. 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 103:29–36

    Article  PubMed  CAS  Google Scholar 

  33. Magnowski P, Seremak-Mrozikiewicz A, Nowak-Markwitz E et al (2010) No association between MTHFR 677C>T polymorphism and ovarian cancer risk in BRCA1 mutation carriers in Wielkopolska region. Ginekol Pol 81:506–510

    PubMed  Google Scholar 

  34. Zintzaras E, Lau J (2008) Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol 61:634–645

    Article  PubMed  Google Scholar 

  35. Ioannidis JP, Patsopoulos NA, Evangelou E (2007) Uncertainty in heterogeneity estimates in meta-analyses. BMJ 335:914–916

    Article  PubMed  Google Scholar 

  36. Kim YI (2000) Methylenetetrahydrofolate reductase polymorphisms, folate, and cancer risk: a paradigm of gene-nutrient interactions in carcinogenesis. Nutr Rev 58:205–209

    Article  PubMed  CAS  Google Scholar 

  37. Kouidhi S, Rouissi K, Khedhiri S et al (2011) MTHFR gene polymorphisms and bladder cancer susceptibility: a meta-analysis including race, smoking status and tumour stage. Asian Pac J Cancer Prev 12:2227–2232

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  39. 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 

  40. Dong LM, Potter JD, White E et al (2008) Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 299:2423–2436

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Gynecology, Changning Maternity and Infant Health Hospital of Shanghai, 773 Wuyi Road, Shanghai, 200051, China

    Chengbin Ma, Yan Liu, Wenying Zhang & Ping Liu

Authors
  1. Chengbin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ping Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, C., Liu, Y., Zhang, W. et al. The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals. Mol Biol Rep 40, 2061–2068 (2013). https://doi.org/10.1007/s11033-012-1970-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1970-8

Keywords

Search

Navigation