SpringerLink
Log in

Association between MSH6 G39E polymorphism and cancer susceptibility: a meta-analysis of 7,046 cases and 34,554 controls

  • Research Article
  • Published:
Tumor Biology

Abstract

Although the MSH6 G39E polymorphism is considered to be a biomarker of hereditary nonpolyposis colorectal cancer (HNPCC), many studies have also found that it may be associated with increased risks of lung, breast, and pancreatic cancers, with inconsistent estimated risks. Here, we performed a comprehensive meta-analysis to assess the associations. We searched published literature from MEDLINE, EMBASE, and CNKI for eligible publications up to Dec. 5, 2013. The final meta-analysis included 10 published studies of 7,046 cases and 34,554 controls for MSH6 G39E. Overall, no significant association was detected between MSH6 G39E and cancer risk (GE + EE vs. GG: OR = 0.92, 95 % CI = 0.81–1.04). Further stratifications, however, showed the MSH6 G39E variant is associated with a decreased risk for cancer in population-based studies (GE + EE vs. GG: OR = 0.80, 95 % CI = 0.60–0.91), and in studies having utilizing large sample sizes (GE + EE vs. GG: OR = 0.87, 95 % CI = 0.85–0.99). No potential publication bias was found among studies. The present meta-analysis identified some statistical evidence for an association between the MSH6 G39E polymorphism and risk of cancer. However, this finding warrants additional validation in large and well-designed prospective studies in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Imyanitov EN, Togo AV, Hanson KP. Searching for cancer-associated gene polymorphisms: promises and obstacles. Cancer Lett. 2004;204:3–14.

    Article  CAS  PubMed  Google Scholar 

  2. Huang WY, Berndt SI, Kang D, Chatterjee N, Chanock SJ, Yeager M, et al. Nucleotide excision repair gene polymorphisms and risk of advanced colorectal adenoma: Xpc polymorphisms modify smoking-related risk. Cancer Epidemiol Biomarkers Prev. 2006;15:306–11.

    Article  CAS  PubMed  Google Scholar 

  3. Hu Z, Shao M, Yuan J, Xu L, Wang F, Wang Y, et al. Polymorphisms in DNA damage binding protein 2 (ddb2) and susceptibility of primary lung cancer in the Chinese: a case-control study. Carcinogenesis. 2006;27:1475–80.

    Article  CAS  PubMed  Google Scholar 

  4. Garcia-Closas M, Malats N, Real FX, Welch R, Kogevinas M, Chatterjee N, et al. Genetic variation in the nucleotide excision repair pathway and bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:536–42.

    Article  CAS  PubMed  Google Scholar 

  5. Berndt SI, Platz EA, Fallin MD, Thuita LW, Hoffman SC, Helzlsouer KJ. Mismatch repair polymorphisms and the risk of colorectal cancer. International journal of cancer Journal international du cancer. 2007;120:1548–54.

    Article  CAS  PubMed  Google Scholar 

  6. Buttin BM, Powell MA, Mutch DG, Babb SA, Huettner PC, Edmonston TB, et al. Penetrance and expressivity of msh6 germline mutations in seven kindreds not ascertained by family history. Am J Hum Genet. 2004;74:1262–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Cederquist K, Emanuelsson M, Wiklund F, Golovleva I, Palmqvist R, Gronberg H. Two Swedish founder msh6 mutations, one nonsense and one missense, conferring high cumulative risk of lynch syndrome. Clin Genet. 2005;68:533–41.

    Article  CAS  PubMed  Google Scholar 

  8. Kastrinos F, Syngal S. Recently identified colon cancer predispositions: Myh and msh6 mutations. Semin Oncol. 2007;34:418–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Jenkins MA. Role of msh6 and pms2 in the DNA mismatch repair process and carcinogenesis. Surg Oncol Clin N Am. 2009;18:625–36.

    Article  PubMed  Google Scholar 

  10. Wu X, Khalpey Z, Cascalho M. Cellular physiology of mismatch repair. Curr Pharm Des. 2004;10:4121–6.

    Article  CAS  PubMed  Google Scholar 

  11. Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, et al. Germline mutation of msh6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet. 1997;17:271–2.

    Article  CAS  PubMed  Google Scholar 

  12. Kolodner RD, Tytell JD, Schmeits JL, Kane MF, Gupta RD, Weger J, et al. Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999;59:5068–74.

    CAS  PubMed  Google Scholar 

  13. Wu Y, Berends MJ, Mensink RG, Kem**a C, Sijmons RH, van Der Zee AG, et al. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with msh6 germline mutations. Am J Hum Genet. 1999;65:1291–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Curtin K, Samowitz WS, Wolff RK, Caan BJ, Ulrich CM, Potter JD, et al. Msh6 g39e polymorphism and CpG island methylator phenotype in colon cancer. Mol Carcinog. 2009;48:989–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, et al. Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis. 2008;29:2132–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Dong X, Li Y, Chang P, Hess KR, Abbruzzese JL, Li D. DNA mismatch repair network gene polymorphism as a susceptibility factor for pancreatic cancer. Mol Carcinog. 2012;51:491–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Conde J, Silva SN, Azevedo AP, Teixeira V, Pina JE, Rueff J, et al. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study. BMC Cancer. 2009;9:344.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Landi S, Gemignani F, Canzian F, Gaborieau V, Barale R, Landi D, et al. DNA repair and cell cycle control genes and the risk of young-onset lung cancer. Cancer Res. 2006;66:11062–9.

    Article  CAS  PubMed  Google Scholar 

  19. Tulupova E, Kumar R, Hanova M, Slyskova J, Pardini B, Polakova V, et al. Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer? Mutat Res. 2008;648:40–5.

    Article  CAS  PubMed  Google Scholar 

  20. Picelli S, Zajac P, Zhou XL, Edler D, Lenander C, Dalen J, et al. Common variants in human CRC genes as low-risk alleles. Eur J Cancer. 2010;46:1041–8.

    Article  CAS  PubMed  Google Scholar 

  21. Shea B, Wells GA, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa scale (nos) for assessing the quality of nonrandomised studies in meta-analyses. 2011: www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed February 17, 2014.

  22. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  23. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed). 1997;315:629–34.

    Article  CAS  Google Scholar 

  24. Campbell PT, Curtin K, Ulrich CM, Samowitz WS, Bigler J, Velicer CM, et al. Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors. Gut. 2009;58:661–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Nicolaides NC, Palombo F, Kinzler KW, Vogelstein B, Jiricny J. Molecular cloning of the n-terminus of GTBP. Genomics. 1996;31:395–7.

    Article  CAS  PubMed  Google Scholar 

  26. Ramensky V, Bork P, Sunyaev S. Human non-synonymous SNPS: server and survey. Nucleic Acids Res. 2002;30:3894–900.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Ng PC, Henikoff S. Sift: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31:3812–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Parc YR, Halling KC, Wang L, Christensen ER, Cunningham JM, French AJ, et al. Hmsh6 alterations in patients with microsatellite instability-low colorectal cancer. Cancer Res. 2000;60:2225–31.

    CAS  PubMed  Google Scholar 

  29. Samowitz WS, Curtin K, Wolff RK, Albertsen H, Sweeney C, Caan BJ, et al. The mlh1–93 g>a promoter polymorphism and genetic and epigenetic alterations in colon cancer. Genes Chromosom Cancer. 2008;47:835–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None

Author information

Authors and Affiliations

  1. Maternity and Child Health Hospital of Yiling District, Yichang, Hubei, China

    Zuming Li, Lihua Kong & Ling Yu

  2. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Jiao Huang, Ke Wang, Shi Chen, Miao Yu & Sheng Wei

Authors
  1. Zuming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lihua Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ke Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sheng Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sheng Wei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Z., Kong, L., Yu, L. et al. Association between MSH6 G39E polymorphism and cancer susceptibility: a meta-analysis of 7,046 cases and 34,554 controls. Tumor Biol. 35, 6029–6037 (2014). https://doi.org/10.1007/s13277-014-1798-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1798-z

Keywords

Search

Navigation