DOI QR코드

DOI QR Code

MTHFR C677T Polymorphism and Ovarian Cancer Risk: A Meta-analysis

  • Ding, Xiao-Ping (Department of Obstetrics and Gynecology, the Second Artillery General Hospital) ;
  • Feng, Li (Department of Obstetrics and Gynecology, the Second Artillery General Hospital) ;
  • Ma, Li (Department of Obstetrics and Gynecology, the Second Artillery General Hospital)
  • Published : 2012.08.31

Abstract

Background: Many studies have investigated possible association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and ovarian cancer risk, but the impact is still unclear owing to the obvious inconsistencies. This study was performed to quantify the strength of the association with a metaanalysis. Methods: We searched the PubMed, Embase, and CNKI databases for studies relating the association between MTHFR C677T polymorphism and ovarian cancer risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment. Results: Finally, eight studies with a total of 3,379 ovarian cancer cases and 4,078 controls were included into this meta-analysis. Overall the showed that MTHFR C677T polymorphism was not associated with ovarian cancer risk under all genetic models ($OR_{T\;versus\;C}$ = 1.03, 95%CI 0.90-1.18; $OR_{TT\;versus\;CC}$ = 1.08, 95%CI 0.79-1.47; $OR_{TT\;versus\;TC+CC}$ = 1.05, 95%CI 0.80-1.37; $OR_{TT+TC\;versus\;CC}$ = 1.05, 95%CI 0.86-1.21). Meta-analyses of studies with confirmation of HWE also showed no significant association. Subgroup analyses by ethnicity showed there was no significant association in the Caucasians but MTHFR C677T polymorphic variant T contributed to increased risk of ovarian cancer in East Asians. No evidence of publication bias was observed. Conclusion: Meta-analyses of available data show that MTHFR C677T polymorphism is not associated with ovarian cancer risk in Caucasians, but the MTHFR polymorphic variant T may contribute to increased risk in East Asians.

Keywords

References

  1. Attia J, Thakkinstian A, D'Este C (2003). Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol, 56, 297-303. https://doi.org/10.1016/S0895-4356(03)00011-8
  2. Bhopal R (2004). Glossary of terms relating to ethnicity and race: for reflection and debate. J Epidemiol Community Health, 58, 441-5. https://doi.org/10.1136/jech.2003.013466
  3. Bhurgri Y, Shaheen Y, Kayani N, et al (2011). Incidence, trends and morphology of ovarian cancer in Karachi (1995-2002). Asian Pac J Cancer Prev, 12, 1567-71.
  4. Burchard EG, Ziv E, Coyle N, et al (2003). The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med, 348, 1170-5. https://doi.org/10.1056/NEJMsb025007
  5. Cannistra SA (2004). Cancer of the ovary. N Engl J Med, 351, 2519-29. https://doi.org/10.1056/NEJMra041842
  6. Clarke-Pearson DL (2009). Clinical practice. Screening for ovarian cancer. N Engl J Med, 361, 170-7. https://doi.org/10.1056/NEJMcp0901926
  7. Cochran WG (1954). The combination of estimates from different experiments. Biometrics, 10, 101-29. https://doi.org/10.2307/3001666
  8. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88. https://doi.org/10.1016/0197-2456(86)90046-2
  9. Diaz-Padilla I, Amir E, Marsh S, et al (2012). Genetic polymorphisms as predictive and prognostic biomarkers in gynecological cancers: a systematic review. Gynecol Oncol, 124, 354-65. https://doi.org/10.1016/j.ygyno.2011.10.034
  10. Dong LM, Potter JD, White E, et al (2008). Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA, 299, 2423-36. https://doi.org/10.1001/jama.299.20.2423
  11. Dong X, Wu J, Liang P, et al (2010). Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer: a meta-analysis. Arch Med Res, 41, 125-33. https://doi.org/10.1016/j.arcmed.2010.01.001
  12. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34. https://doi.org/10.1136/bmj.315.7109.629
  13. 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, 111-3. https://doi.org/10.1038/ng0595-111
  14. 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, 569-73. https://doi.org/10.7314/APJCP.2012.13.2.569
  15. 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, 2313-6. https://doi.org/10.1016/S0959-8049(00)00306-3
  16. Goyette P, Sumner JS, Milos R, et al (1994). Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet, 7, 195-200. https://doi.org/10.1038/ng0694-195
  17. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60. https://doi.org/10.1136/bmj.327.7414.557
  18. Holmes MV, Newcombe P, Hubacek JA, et al (2011). Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet, 378, 584-94. https://doi.org/10.1016/S0140-6736(11)60872-6
  19. Huang M, Chen Q, Xiao J, et al (2012). CYP1A1 Ile(462)Val is a risk factor for ovarian cancer development. Cytokine, 58, 73-8. https://doi.org/10.1016/j.cyto.2011.12.025
  20. Ioannidis JP, Patsopoulos NA, Evangelou E (2007). Uncertainty in heterogeneity estimates in meta-analyses. BMJ, 335, 914-6. https://doi.org/10.1136/bmj.39343.408449.80
  21. 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. https://doi.org/10.1007/s10549-006-9417-3
  22. Jemal A, Siegel R, Xu J, et al (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  23. Jin F, Qu LS, Shen XZ (2009). Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis. Diagn Pathol, 4, 39. https://doi.org/10.1186/1746-1596-4-39
  24. Khanra K, Panda K, Bhattacharya C, et al (2012). Association of two polymorphisms of DNA polymerase Beta in exon-9 and exon-11 with ovarian carcinoma in India. Asian Pac J Cancer Prev, 13, 1321-4. https://doi.org/10.7314/APJCP.2012.13.4.1321
  25. Kim YI (2005). 5,10-Methylenetetrahydrofolate reductase polymorphisms and pharmacogenetics: a new role of single nucleotide polymorphisms in the folate metabolic pathway in human health and disease. Nutr Rev, 63, 398-407. https://doi.org/10.1111/j.1753-4887.2005.tb00377.x
  26. Kiyohara C, Horiuchi T, Takayama K, et al (2011). Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population. BMC Cancer, 11, 459. https://doi.org/10.1186/1471-2407-11-459
  27. 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, 506-10.
  28. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  29. Pawlik P, Mostowska A, Lianeri M, et al (2011). Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population. Mol Biol Rep, 39, 5553-60.
  30. Pennington KP, Swisher EM (2012). Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol, 124, 347-53. https://doi.org/10.1016/j.ygyno.2011.12.415
  31. Petitti DB. (2000) Meta-analysis, decision analysis, and cost effectiveness analysis: methods for quantitative synthesis in medicine(2nded). New York, NY: Oxford University Press.
  32. 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, 422-6. https://doi.org/10.1159/000331131
  33. Salanti G, Amountza G, Ntzani EE, et al (2005). Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur J Hum Genet, 13, 840-8. https://doi.org/10.1038/sj.ejhg.5201410
  34. Sharp L, Little J (2004). Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol, 159, 423-43. https://doi.org/10.1093/aje/kwh066
  35. 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. https://doi.org/10.1136/bmj.316.7129.469
  36. Taioli E, Garza MA, Ahn YO, et al (2009). Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. Am J Epidemiol, 170, 1207-21. https://doi.org/10.1093/aje/kwp275
  37. Terry KL, Tworoger SS, Goode EL, et al (2010). MTHFR polymorphisms in relation to ovarian cancer risk. Gynecol Oncol, 119, 319-24. https://doi.org/10.1016/j.ygyno.2010.08.007
  38. Thompson SG, Higgins J (2002). How should meta, regression analyses be undertaken and interpreted? Stat Med, 21, 1559-73. https://doi.org/10.1002/sim.1187
  39. Tobias A (1999). Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull, 8, 15-7.
  40. 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, 1133-40. https://doi.org/10.1038/ejcn.2011.99
  41. Wu Y, Zhang JY, Zuo WJ (2007). Association between genetic polymorphisms of methylenetetrahydrofolate reductase C677T and susceptibility to ovarian cancer. Xian Dai Fu Chan Ke Jin Zhan, 16, 811-3.
  42. Zhang J, Qiu LX, Wang ZH, et al (2010). MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls. Breast Cancer Res Treat, 123, 549-55. https://doi.org/10.1007/s10549-010-0783-5
  43. 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, 6203-11. https://doi.org/10.1007/s11033-011-1439-1

Cited by

  1. MTHFR genetic polymorphisms may contribute to the risk of chronic myelogenous leukemia in adults: a meta-analysis of 12 genetic association studies vol.35, pp.5, 2014, https://doi.org/10.1007/s13277-013-1554-9
  2. Association between MTHFR Polymorphisms and Acute Myeloid Leukemia Risk: A Meta-Analysis vol.9, pp.2, 2014, https://doi.org/10.1371/journal.pone.0088823
  3. Evaluation of the MTHFR C677T Polymorphism as a Risk Factor for Colorectal Cancer in Asian Populations vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8093
  4. The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis vol.53, pp.5, 2017, https://doi.org/10.1134/S1022795417040044