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

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.