title: The common variant rs4444235 near BMP4 confers genetic susceptibility of colorectal cancer: an updated meta-analysis based on a comprehensive statistical strategy.
abstract: OBJECTIVE
  We performed an updated meta-analysis, using a comprehensive strategy of a logistic regression and a model-free approach, to evaluate more precisely the role of the rs4444235 variant near the Bone morphogenetic protein-4 (BMP4) gene in susceptibility to colorectal cancer (CRC).
  
  
  METHODS
  A total of 19 studies with 28770 cases and 28234 controls were included. Metagen system with logistic regression was applied to choose the most plausible genetic model for rs4444235. Generalized odds ratio (ORG) metric was used to provide a global test of relationship between rs4444235 and CRC risk.
  
  
  RESULTS
  Metagen analysis suggested the rs4444235 fitted best to an additive model. In assessment of the additive model, heterogeneity was observed (P = 0.059, I2 = 36.1), and pooled per-allele OR was 1.08 (95% CI = 1.05-1.11). Based on the model-free approach, pooled ORG was 1.09 (95% CI = 1.05-1.14) under a random-effect model. Stratified analyses suggested heterogeneity could be in part explained by population ethnicity, study design, sources of controls, and sample size. Sensitivity analysis further supported the robust stability of the current results, by showing similar pooled estimates before and after sequential removal of each study.
  
  
  CONCLUSIONS
  This meta-analysis provides a robust estimate of the positive association between the rs4444235 and CRC risk and further emphasizes the importance of the rs4444235 in CRC risk prediction.
authors.affiliation: Guangdong Key Laboratory of Molecular Epidemiology and Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Qinji
authors.initials: Q
authors.lastname: Su
authors.affiliation: Guangdong Key Laboratory of Molecular Epidemiology and Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory of Molecular Epidemiology and Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lin
authors.affiliation: Guangdong Key Laboratory of Molecular Epidemiology and Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Guangdong Key Laboratory of Molecular Epidemiology and Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Chen
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4