title: Association between MutL homolog 1 polymorphisms and the risk of colorectal cancer: a meta-analysis.
abstract: OBJECTIVE
  As one of the most essential components of mismatch repair system, MutL homolog 1 (MLH1) plays an increasingly implicated role in initiation and promotion of colorectal carcinogenesis, with germ-line mutations in different loci. However, whether a single genetic variant in MLH1 could predict the risk of cancer was still under doubt and recent studies yielded inconsistent results. Therefore, this meta-analysis aimed at investigating the association between MLH1 single-nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) risks.
  
  
  METHODS
  A systematic literature search of PubMed, MEDLINE, Web of Science and BIOSIS databases was performed to obtain all available SNPs and studies. We focused on three SNPs (rs1800734, rs1799977 and rs63750448) with the most included studies and conducted overall and subgroup analyses after data extraction.
  
  
  RESULTS
  A total of 37,347, 29,114 and 2722 patients in case and control groups were meta-analyzed in four genetic models (AA vs. BB, AB vs. BB, AA+AB vs. BB and AA vs. BB+AB) for each SNP. The overall results suggested that the mutation in rs63750447 predicted a higher CRC risk (AB vs. BB: OR 2.283, 95 % CI 1.612-3.232, P = 0.000; AA+AB vs. BB: OR 2.291, 95 % CI 1.618-3.244, P = 0.000), while rs1800734 and rs1799977 were not associated with CRC risks. Subgroup analysis according to study area, quality score and genotyping technique revealed the similar results.
  
  
  CONCLUSIONS
  As the first meta-analysis reporting the association between rs63750448 and CRC risk, the A allele substitution might be a risk factor for CRC. Additionally, there was no persuasive evidence showing that SNPs of rs1800734 and rs1799977 were related to CRC susceptibility.
authors.affiliation: The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China.|Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
authors.forename: Zhujing
authors.initials: Z
authors.lastname: Shen
authors.affiliation: The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China.|Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Yeting
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China.|Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China.|Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Dikai
authors.initials: D
authors.lastname: Bei
authors.affiliation: The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China.|Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Shen
authors.affiliation: The Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, The Key Laboratory of Molecular Biology in Medical Sciences of Zhejiang Province, Cancer Institute, Hangzhou, Zhejiang, China. dingkefeng@zju.edu.cn.|Department of Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. dingkefeng@zju.edu.cn.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Ding
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1
keywords: Colorectal cancer; MLH1; Meta-analysis; Polymorphism