title: Common genetic variants in Wnt signaling pathway genes as potential prognostic biomarkers for colorectal cancer.
abstract: Compelling evidence has implicated the Wnt signaling pathway in the pathogenesis of colorectal cancer. We assessed the use of tag single nucleotide polymorphisms (tSNPs) in adenomatous polyposis coli (APC)/β-catenin (CTNNB1) genes to predict outcomes in patients with colorectal cancer. We selected and genotyped 10 tSNP to predict common variants across entire APC and CTNNB1 genes in 282 colorectal cancer patients. The associations of these tSNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis. The 5-year overall survival rate was 68.3%. Survival tree analysis identified a higher-order genetic interaction profile consisting of the APC rs565453, CTNNB1 2293303, and APC rs1816769 that was significantly associated with overall survival. The 5-year survival overall rates were 89.2%, 66.1%, and 58.8% for the low-, medium-, and high-risk genetic profiles, respectively (log-rank P = 0.001). After adjusting for possible confounders, including age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, perineural invasion, and lymph node involvement, the genetic interaction profile remained significant. None of the studied SNPs were individually associated with distant metastasis-free survival and overall survival. Our results suggest that the genetic interaction profile among Wnt pathway SNPs might potentially increase the prognostic value in outcome prediction for colorectal cancer.
authors: Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.
authors: Wen-Chien
authors: WC
authors: Ting
authors: Lu-Min
authors: LM
authors: Chen
authors: Jiunn-Bey
authors: JB
authors: Pao
authors: Ying-Pi
authors: YP
authors: Yang
authors: Bang-Jau
authors: BJ
authors: You
authors: Ta-Yuan
authors: TY
authors: Chang
authors: Yu-Hsuan
authors: YH
authors: Lan
authors: Hong-Zin
authors: HZ
authors: Lee
authors: Bo-Ying
authors: BY
authors: Bao
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015996:Survival Rate; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics*
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D004273:DNA, Neoplasm; D051176:beta Catenin