Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Basic Research

MTHFR polymorphism and the risk of prostate cancer: a meta-analysis of case–control studies

Prostate Cancer and Prostatic Diseases volume 15, pages 244–249 (2012)Cite this article

Subjects

Abstract

BACKGROUND:

5,10-Methylenetetrahydrofolate reductase (MTHFR) polymorphisms implicated in the cancer development, but the published studies had yielded inconsistent results.

METHODS:

Pubmed was searched for all published case–control studies about MTHFR polymorphisms and prostate cancer risk.

RESULTS:

In all, 13 studies including 5872 cases and 6255 controls described C677T genotypes, among which 9 articles, containing 2847 cases and 3657 controls described A1298C genotypes, were involved in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR polymorphisms and prostate cancer risk, heterogeneity, publication bias and sensitivity were also calculated. Overall, meta-analysis indicated that the 677T allele was more likely to exert protective effect on prostate cancer risk (random-effects pooled OR, 0.78 (0.64–0.96); P=0.016 (P=0.033 for heterogeneity studies)) in a recessive genetic model, no associations were found in other genetic models or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on high or low aggressive prostate cancer. No evidence of an association of MTHFR A1298C polymorphism with prostate cancer was found.

CONCLUSIONS:

C677T of the MTHFR gene may provide protective effects on susceptibility to prostate cancer risk.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hsing AW, Chokkalingam AP . Prostate cancer epidemiology. Front Biosci 2006; 11: 1388–1413.

    Article  CAS  PubMed  Google Scholar 

  2. Dobosy JR, Roberts JL, Fu VX, Jarrard DF . The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia. J Urol 2007; 177: 822–831.

    Article  CAS  PubMed  Google Scholar 

  3. Murphy TM, Perry AS, Lawler M . The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer. Endocr Relat Cancer 2008; 15: 11–25.

    Article  CAS  PubMed  Google Scholar 

  4. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111–113.

    Article  CAS  PubMed  Google Scholar 

  5. Weisberg IS, Jacques PF, Selhub J, Bostom AG, Chen Z, Curtis Ellison R et al. The 1298A–C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 2001; 156: 409–415.

    Article  CAS  PubMed  Google Scholar 

  6. Nelson WG, De Marzo AM, Isaacs WB . Prostate cancer. New Engl J Med 2003; 49: 366–381.

    Article  Google Scholar 

  7. Lee WH, Isaacs WB, Bova GS, Nelso WG . CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker. Cancer Epidemiol Biomarkers Prev 1997; 6: 443–450.

    CAS  PubMed  Google Scholar 

  8. Fenech M . The role of folic acid and Vitamin B12 in genomic stability of human cells. Mutat Res 2001; 475: 57–67.

    Article  CAS  PubMed  Google Scholar 

  9. Choi SW, Friso S . Interaction between folate and methylene-tetrahydrofolate reductase gene in cancer. In: Choi SW, Friso S, (eds). Nutrient-Gene Interactions in Cancer. CRC Press, Florida, USA, 2006; p: 57–74.

    Chapter  Google Scholar 

  10. Dong LM, Potter JD, White E, Ulrich CM, Cardon LR, Peters U . Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 2008; 299: 2423–2436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ulrich CM . Genetic variability in folate-mediated one-carbon metabolism and cancer risk. In: Choi SW, Friso S, (eds). Nutrient-Gene Interactions in Cancer. CRC Press, Florida, USA, 2006, pp 75–91.

    Chapter  Google Scholar 

  12. Bai JL, Zheng MH, Xia X, Ter-Minassian M, Chen YP, Chen F . MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: A meta-analysis of 3511 cases and 2762 controls. Eur J cancer 2009; 45: 1443–1449.

    Article  CAS  PubMed  Google Scholar 

  13. Collin SM, Metcalfe C, Zuccolo L, Lewis SJ, Chen L, Cox A et al. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Cance Epidemiol Biomarkers Prev 2009; 18: 2528–2539.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  15. Aurelio T . Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 1999; 8: 15–17.

    Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kimura F, Franke KH, Steinhoff C, Golka K, Roemer HC, Anastasiadis AG et al. Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma. Prostate 2000; 45: 225–231.

    Article  CAS  PubMed  Google Scholar 

  18. Heijmans BT, Boer JM, Suchiman HE, Cornelisse CJ, Westendorp RG, Kromhout D et al. A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res 2003; 63: 1249–1253.

    CAS  PubMed  Google Scholar 

  19. Cicek MS, Nock NL, Li L, Conti DV, Casey G, Witte JS . Relationship between methylenetetrahydrofolate reductase C677T and A1298C genotypes and haplotypes and prostate cancer risk and aggressiveness. Cancer Epidemiol Biomarkers Prev 2004; 13: 1331–1336.

    CAS  PubMed  Google Scholar 

  20. Singal R, Ferdinand L, Das PM, Reis IM, Schlesselman JJ . Polymorphisms in the methylenetetrahydrofolate reductase gene and prostate cancer risk. Int J Oncol 2004; 25: 1465–1471.

    CAS  PubMed  Google Scholar 

  21. Van Guelpen BR, Wirén SM, Bergh AR, Hallmans G, Stattin PE, Hultdin J . Polymorphisms of methylenetetrahydrofolate reductase and the risk of prostate cancer: a nested case-control study. Eur J Cancer Prev 2006; 15: 46–50.

    Article  CAS  PubMed  Google Scholar 

  22. Johansson M, Van Guelpen B, Hultdin J, Wiklund F, Adami HO, Bälter K et al. The MTHFR 677C–T polymorphism and risk of prostate cancer: results from the CAPS study. Cancer Causes Control 2007; 18: 1169–1174.

    Article  PubMed  Google Scholar 

  23. Reljic A, Simundic AM, Topic E, Nikolac N, Justinic D, Stefanovic M . The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cancer risk: the Croatian case-control study. Clin Biochem 2007; 40: 981–985.

    Article  CAS  PubMed  Google Scholar 

  24. Marchal C, Redondo M, Reyes-Engel A, Perea-Milla E, Gaitan MJ, Machuca J et al. Association between polymorphisms of folate-metabolizing enzymes and risk of prostate cancer. Eur J Surg Oncol 2008; 34: 805–810.

    Article  CAS  PubMed  Google Scholar 

  25. 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: 3612–3614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Muslumanoglu MH, Tepeli E, Demir S, Uludag A, Uzun D, Atli E et al. The analysis of the relationship between A1298C and C677T polymorphisms of the MTHFR gene with prostate cancer in Eskisehir population. Genet Test Mol Biomarkers 2009; 13: 641–645.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. Cai D, Ning L, Pan C, Liu X, Bu R, Chen X et al. Association of polymorphisms in folate metabolic genes and prostate cancer risk: a case-control study in a Chinese population. J Genet 2010; 89: 263–267.

    Article  PubMed  Google Scholar 

  29. Wu HC, Chang CH, Tsai RY, Lin CH, Wang RF, Tsai CW et al. Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in taiwan. Anticancer Res 2010; 30: 3573–3577.

    CAS  PubMed  Google Scholar 

  30. Matsuo K, Suzuki R, Hamajima N, Ogura M, Kagami Y, Taji H et al. Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma. Blood 2001; 97: 3205–3209.

    Article  CAS  PubMed  Google Scholar 

  31. Chen J, Giovannucci E, Hankinson SE, Ma J, Willett WC, Spiegelman D et al. A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma. Carcinogenesis 1998; 19: 2129–2132.

    Article  CAS  PubMed  Google Scholar 

  32. Pavillard V, Drbal AA, Swaine DJ, Phillips RM, Double JA, Nicolaou A . Analysis of cell-cycle kinetics and sulfur amino acid metabolism in methioninedependent tumor cell lines; the effect of homocysteine supplementation. Biochem Pharmacol 2004; 67: 1587–1599.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (no._81001185), Universities Natural Science Foundation of Jiangsu Province (no._10KJB310011) and the Social Development Foundation of Suzhou (no_YJS0905).

Author information

Author notes

  1. X-L Li and J-H Xu: These authors contribute equally to the work.

Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, China

    X-L Li

  2. Department of Radiotherapy, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

    J-H Xu

Authors
  1. X-L Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J-H Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X-L Li.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, XL., Xu, JH. MTHFR polymorphism and the risk of prostate cancer: a meta-analysis of case–control studies. Prostate Cancer Prostatic Dis 15, 244–249 (2012). https://doi.org/10.1038/pcan.2012.5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2012.5

Keywords

This article is cited by

Search

Advanced search

Quick links