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MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

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Abstract

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR = 0.94, 95 % CI = 0.71–1.24, P = 0.65; CT vs. CC: OR = 1.03, 95 % CI = 0.93–1.14, P = 0.57; TT/CT vs. CC: OR = 1.01, 95 % CI = 0.88–1.16, P = 0.87; TT vs. CC/CT: OR = 0.93, 95 % CI = 0.72–1.20, P = 0.58. For A1298C: CC vs. AA: OR = 1.05, 95 % CI = 0.88–1.25, P = 0.65; CA vs. AA: OR = 0.98, 95 % CI = 0.88–1.08, P = 0.66; CC/CA vs. AA: OR = 0.99, 95 % CI = 0.90–1.09, P = 0.85; CC vs. AA/CA: OR = 1.06, 95 % CI = 0.90–1.26, P = 0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.

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References

  1. Stern LL, Mason JB, Selhub J et al (2000) Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev 9:849–853

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Duthie SJ (1999) Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull 55:578–592

    Article  PubMed  CAS  Google Scholar 

  4. Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10:66–88

    Article  PubMed  CAS  Google Scholar 

  5. Mason JB, Choi SW (2000) Folate and carcinogenesis: developing a unifying hypothesis. Adv Enzyme Regul 40:127–141

    Article  PubMed  CAS  Google Scholar 

  6. La Vecchia C, Negri E, Pelucchi C et al (2002) Dietary folate and colorectal cancer. Int J Cancer 102:545–547

    Article  PubMed  Google Scholar 

  7. McCann SE, Freudenheim JL, Marshall JR et al (2000) Diet in the epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control 11:965–974

    Article  PubMed  CAS  Google Scholar 

  8. Goyette P, Pai A, Milos R et al (1998) Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 9:652–656

    Article  PubMed  CAS  Google Scholar 

  9. Angeline T, Jeyaraj N, Granito S et al (2004) Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among Tamilians. Exp Mol Pathol 77:85–88

    Article  PubMed  CAS  Google Scholar 

  10. Weisberg IS, Jacques PF, Selhub J et al (2001) The 129XA-C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 156:409–415

    Article  PubMed  CAS  Google Scholar 

  11. Weisberg I, Tran P, Christensen B et al (1998) A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 64:169–172

    Article  PubMed  CAS  Google Scholar 

  12. 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 

  13. Levine AJ, Figueiredo JC, Lee W et al (2010) Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry. Cancer Epidemiol Biomarkers Prev 19:89–100

    Article  PubMed  CAS  Google Scholar 

  14. Kim J, Cho YA, Kim DH et al (2012) Dietary intake of folate and alcohol, MTHFR C677T polymorphism, and colorectal cancer risk in Korea. Am J Clin Nutr 95:405–412

    Article  PubMed  CAS  Google Scholar 

  15. Bai JL, Zheng MH, Xia X et al (2009) MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: a meta-analysis of 3511 cases and 2762 controls. Eur J Cancer 45:1443–1449

    Article  PubMed  CAS  Google Scholar 

  16. 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 

  17. Xu WH, Shrubsole MJ, Xiang YB et al (2007) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 16:281–287

    Article  PubMed  CAS  Google Scholar 

  18. Hosseini M, Houshmand M, Ebrahimi A (2011) MTHFR polymorphisms and breast cancer risk. Arch Med Sci 7:134–137

    Article  PubMed  CAS  Google Scholar 

  19. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics. CA Cancer J Clin 2008(58):71–96

    Article  Google Scholar 

  20. 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 

  21. 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 

  22. 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 

  23. 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 

  24. 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 

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

    Article  PubMed  CAS  Google Scholar 

  26. Zintzaras E, Ioannidis JP (2005) Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol 28:123–137

    Article  PubMed  Google Scholar 

  27. 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 

  28. 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 

  29. Galbiatti AL, Ruiz MT, Maniglia JV et al (2012) Head and neck cancer: genetic polymorphisms and folate metabolism. Braz J Otorhinolaryngol 78:132–139

    Article  PubMed  Google Scholar 

  30. Zhao P, Lin F, Li Z et al (2011) Folate intake, methylenetetrahydrofolate reductase polymorphisms, and risk of esophageal cancer. Asian Pac J Cancer Prev 12:2019–2023

    PubMed  Google Scholar 

  31. Zhang Y, Chen GQ, Ji Y et al (2012) Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma. Mol Biol Rep 39:6203–6211

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China

    Lu Liu, Shao-Guang Liao & Ya-Jie Wang

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  1. Lu Liu
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  2. Shao-Guang Liao
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  3. Ya-Jie Wang
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Correspondence to Ya-Jie Wang.

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Lu Liu and Shao-Guang Liao equally contributed to this study.

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Liu, L., Liao, SG. & Wang, YJ. MTHFR polymorphisms and ovarian cancer risk: a meta-analysis. Mol Biol Rep 39, 9863–9868 (2012). https://doi.org/10.1007/s11033-012-1852-0

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  • DOI: https://doi.org/10.1007/s11033-012-1852-0

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