title: Association between MLH1 -93G>a polymorphism and risk of colorectal cancer.
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
  OR = 2.29, 95% CI = 1.78-2.96). Egger's test did not show any evidence of publication bias.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Sima
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Chunhui
authors.initials: C
authors.lastname: Ni
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D016206:Databases, Bibliographic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017594:Publication Bias; D012306:Risk
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1