title: A common SMAD7 variant is associated with risk of colorectal cancer: evidence from a case-control study and a meta-analysis.
abstract: BACKGROUND
  A common genetic variant, rs4939827, located in SMAD7, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.
  
  
  RESULTS
  We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19-1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all P for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.
  
  
  CONCLUSIONS
  Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.
authors.affiliation: Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Song
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.forename: Weiguo
authors.initials: W
authors.lastname: Hu
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
authors.forename: Hongyun
authors.initials: H
authors.lastname: Gong
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Xiawen
authors.initials: X
authors.lastname: Zheng
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Shengyu
authors.initials: S
authors.lastname: Duan
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Rui
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D051906:Smad7 Protein / Q000235:genetics*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein