Association between MLH1 -93G>a polymorphism and risk of colorectal cancer

PLoS One. 2012;7(11):e50449. doi: 10.1371/journal.pone.0050449. Epub 2012 Nov 30.

Abstract

Background: The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective: The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods: To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results: The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01-1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01-1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94-3.28; AG versus GG: OR = 1.29, 95% CI = 1.10-1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24-1.68; AA versus

Ag/gg: OR = 2.29, 95% CI = 1.78-2.96). Egger's test did not show any evidence of publication bias.

Conclusion: Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Alleles
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Databases, Bibliographic
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Microsatellite Instability*
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Publication Bias
  • Risk

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MutL Protein Homolog 1

Grants and funding

This study was partially supported by National Natural Science Foundation of China (81102089), National Natural Science Foundation of Jiangsu Province (BK2011773), the Key Program for Basic Research of Jiangsu Provincial Department of Education (11KJB330002), the Practice Innovation Training Program Projects for the Jiangsu College Students (2011), and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.