A meta-analysis of the prevalence of somatic mutations in the hMLH1 and hMSH2 genes in colorectal cancer

Colorectal Dis. 2012 Mar;14(3):e80-9. doi: 10.1111/j.1463-1318.2011.02858.x.

Abstract

Aim: The study aimed to understand better the somatic mutations in the human MutL Homolog 1 (hMLH1) and human MutS Homolog 2 (hMSH2) genes in colorectal cancer (CRC) and to investigate the differences derived from ethnicity, family history, detection method and microsatellite instability (MSI).

Method: The terms 'hMSH2' or 'hMLH1' and 'colorectal cancer' 'colorectal carcinoma' or 'colorectal tumour' were searched in the PubMed, Springer, Lippincott, Williams & Wilkins and HighWire Press databases for the publication period December 1993 to September 2010. The Comprehensive Meta Analysis V2 software (Biostat Inc.) was used to explore the prevalence and 95% confidence intervals.

Results: The prevalence of somatic mutations in the hMLH1 and hMSH2 genes in CRC was 0.15 (95% CI 0.10-0.22) and 0.10 (95% CI 0.07-0.16), respectively. A higher prevalence of somatic mutations in hMSH2 was found in hereditary non-polyposis CRC than in sporadic CRC: 0.36 (95% CI 0.14-0.67) and 0.10 (95% CI 0.07-0.13) respectively. In addition, a higher prevalence of somatic mutations in the hMLH1 gene was observed relative to hMSH2 in the European group. The prevalence was higher in the high-level instability (MSI-H) group than in both the low-level instability (MSI-L) and the microsatellite stable (MSS) groups.

Conclusion: Somatic mutations in the hMLH1 and hMSH2 genes play a vital role in CRC and a high prevalence was found in this meta-analysis. Furthermore, more studies are needed which focus on somatic mutations in the American population and in patients with MSI-L and MSS.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Asia
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics*
  • Europe
  • Genetic Markers
  • Humans
  • Microsatellite Instability
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • Mutation*
  • North America
  • Nuclear Proteins / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Genetic Markers
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein