title: MLH1 promoter methylation frequency in colorectal cancer patients and related clinicopathological and molecular features.
abstract: OBJECTIVE
  To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.
  
  
  METHODS
  A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated.
  
  
  RESULTS
  The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8-24.1%). They were 18.7% (95% CI: 14.7-23.6%) and 16.4% (95% CI: 11.9-22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215-2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715-5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464-3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717-53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427-34.631; P<0.001) and 9.419 (95% CI: 2.613-33.953; P = 0.001), respectively).
  
  
  CONCLUSIONS
  The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.
authors.affiliation: Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, Heilongjiang Province, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yao
authors.forename: Yibaina
authors.initials: Y
authors.lastname: Wang
authors.forename: Fulan
authors.initials: F
authors.lastname: Hu
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Liying
authors.initials: L
authors.lastname: Jiang
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Da
authors.initials: D
authors.lastname: Wang
authors.forename: Guizhi
authors.initials: G
authors.lastname: Sun
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017594:Publication Bias; D012737:Sex Factors; D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D018631:ras Proteins
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