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Cervical cancer with polymorphism in MTHFR C677T gene: a systematic review and meta-analysis

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Abstract

To perform a meta-analysis investigating the association of MTHFR C677T polymorphism and susceptibility of cervical cancer. All case–control studies published in English and Chinese with estimates of the relationship between MTHFR C677T polymorphism and risk of cervical cancer were analyzed using odds ratio (OR) with 95 % confidence interval (CI). A total of 10 studies (2,023 cases and 2,570 controls) were included in the meta-analysis. No significant association was observed between T allele and C allele (OR = 0.90; 95 %CI = 0.70–1.17; P = 0.43), and for genotype TT versus CC (OR = 1.09; 95 %CI = 0.74–1.61; P = 0.67), CT versus CC (OR = 0.95; 95 %CI = 0.75–1.20; P = 0.65), CT + TT versus CC (OR = 0.91; 95 %CI = 0.66–1.24; P = 0.55). The current meta-analysis results suggest that the MTHFR C677T polymorphism may not be associated with cervical cancer.

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References

  1. Seoud M, Tjalma WA, Ronsse V (2011) Cervical adenocarcinoma: moving towards better prevention. Vaccine 29(49):9148–9158

    Article  PubMed  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimatesof worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Article  PubMed  CAS  Google Scholar 

  3. Mutchinick OM, López MA, Luna L, Waxman J, Babinsky VE (1999) High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects. Mol Genet Metab 68(4):461–467

    Article  PubMed  CAS  Google Scholar 

  4. Uehara SK, Rosa G (2008) Association of homocysteinemia with high concentrations of serum insulin and uric acid in Brazilian subjects with metabolic syndrome genotyped for C677T polymorphism in the methylenetetrahydrofolate reductase gene. Nutr Res 28(11):760–766

    Article  PubMed  CAS  Google Scholar 

  5. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113

    Article  PubMed  CAS  Google Scholar 

  6. Kim YI (1999) Folate and cancer prevention: a new medical application of folate beyond hyperhomocysteinemia and neural tube defects. Nutr Rev 57(10):314–321

    PubMed  CAS  Google Scholar 

  7. Lambropoulos AF, Agorastos T, Foka ZJ, Chrisafi S, Constantinidis TC, Bontis J, Kotsis A (2003) Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia. Cancer Lett 191(2):187–191

    Article  PubMed  CAS  Google Scholar 

  8. Ho CH, Kuo BI, Kong CW, Chau WK, Hsu HC, Gau JP, Yu YB (2005) Influence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, B vitamins and other factors on plasma homocysteine and risk of thromboembolic disease in Chinese. J Chin Med Assoc 68(12):560–565

    Article  PubMed  CAS  Google Scholar 

  9. Sull JW, Jee SH, Yi S, Lee JE, Park JS, Kim S, Ohrr H (2004) The effect of methylenetetrahydrofolate reductase polymorphism C677T on cervical cancer in Korean women. Gynecol Oncol 95(3):557–563

    Article  PubMed  CAS  Google Scholar 

  10. Zoodsma M, Nolte IM, Schipper M, Oosterom E, van der Steege G, de Vries EG, te Meerman GJ, van der Zee AG (2005) Methylenetetrahydrofolate reductase (MTHFR) and susceptibility for (pre)neoplastic cervical disease. Hum Genet 116(4):247–254

    Article  PubMed  CAS  Google Scholar 

  11. Kang S, Kim JW, Kang GH, Park NH, Song YS, Kang SB, Lee HP (2005) Polymorphism in folate- and methionine-metabolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer. Gynecol Oncol 96(1):173–180

    Article  PubMed  CAS  Google Scholar 

  12. Xiaochen M, Jintao W, Qin Z, Lin D, Yuying C, Zhimin W, Juanjuan D (2006) Relationship between Methylenetetrahydrofolate reductase polymorphism and cervical cancer susceptibility. Chin J Public Health I2(22):1427–1428

    Google Scholar 

  13. Shekari M, Sobti RC, Kordi Tamandani DM, Suri V (2008) Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population. Arch Gynecol Obstet 278(6):517–524

    Article  PubMed  CAS  Google Scholar 

  14. Mostowska A, Myka M, Lianeri M, Roszak A, Jagodziński PP (2011) Folate and choline metabolism gene variants and development of uterine cervical carcinoma. Clin Biochem 44(8–9):596–600

    Article  PubMed  CAS  Google Scholar 

  15. Tong SY, Kim MK, Lee JK, Lee JM, Choi SW, Friso S, Song ES, Lee KB, Lee JP (2011) Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12. Cancer Causes Control 22(1):63–72

    Article  PubMed  Google Scholar 

  16. 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(8–9):422–426

    Article  PubMed  CAS  Google Scholar 

  17. von Keyserling H, Bergmann T, Schuetz M, Schiller U, Stanke J, Hoffmann C, Schneider A, Lehrach H, Dahl A, Kaufmann AM (2011) Analysis of 4 single-nucleotide polymorphisms in relation to cervical dysplasia and cancer development using a high-throughput ligation-detection reaction procedure. Int J Gynecol Cancer 21(9):1664–1671

    Article  Google Scholar 

  18. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  19. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  20. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Controlled Clin Trials 7(3):177–188

    Article  PubMed  CAS  Google Scholar 

  21. Sterne JA, Egger M, Smith GD (2001) Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ 323:101–105

    Article  PubMed  CAS  Google Scholar 

  22. Zheng YZ, Tong J, Do XP, Pu XQ, Zhou BT (2000) Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population. Br J Haematol 109(4):870–874

    Article  PubMed  CAS  Google Scholar 

  23. Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93(1):7–9

    Article  PubMed  CAS  Google Scholar 

  24. van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels FJ, Eskes TK, van den Heuvel LP, Mariman EC, den Heyer M, Rozen R, Blom HJ (1995) Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 346(8982):1070–1071

    Article  PubMed  Google Scholar 

  25. Brugada R, Marian AJ (1997) A common mutation in methylenetetrahydrofolate reductase gene is not a major risk of coronary artery disease or myocardial infarction. Atherosclerosis 128(1):107–112

    Article  PubMed  CAS  Google Scholar 

  26. Ma J, Stampfer MJ, Giovannucci E, Artigas C, Hunter DJ, Fuchs C, Willett WC, Selhub J, Hennekens CH, Rozen R (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 57(6):1098–1102

    PubMed  CAS  Google Scholar 

  27. Ulrich CM, Kampman E, Bigler J, Schwartz SM, Chen C, Bostick R, Fosdick L, Beresford SA, Yasui Y, Potter JD (1999) Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? Cancer Epidemiol Biomarkers Prev 8(8):659–668

    PubMed  CAS  Google Scholar 

  28. Levine AJ, Siegmund KD, Ervin CM, Diep A, Lee ER, Frankl HD, Haile RW (2000) The methylenetetrahydrofolate reductase 677C –> T polymorphism and distal colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 9(7):657–663

    PubMed  CAS  Google Scholar 

  29. Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M (1999) Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 8(6):513–518

    PubMed  CAS  Google Scholar 

  30. Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA, Morgan G (1999) Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci U S A 96(22):12810–12815

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Health Informatics, School of Health Services Management, Anhui Medical University, 69 Meishan Road, Hefei, 230032, Anhui, China

    Xiao-juan Xu & De-bin Wang

  2. Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, 69 Meishan Road, Hefei, 230032, Anhui, China

    Li-wei Zou

Authors
  1. Xiao-juan Xu
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  2. Li-wei Zou
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Correspondence to De-bin Wang.

Additional information

Xiao-juan Xu and Li-wei Zou contributed equally to this study.

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Xu, Xj., Zou, Lw. & Wang, Db. Cervical cancer with polymorphism in MTHFR C677T gene: a systematic review and meta-analysis. Mol Biol Rep 40, 255–262 (2013). https://doi.org/10.1007/s11033-012-2056-3

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  • DOI: https://doi.org/10.1007/s11033-012-2056-3

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