Common Genetic Variants in Wnt Signaling Pathway Genes as Potential Prognostic Biomarkers for Colorectal Cancer

Autor: Bang Jau You, Yu-Hsuan Lan, Lu Min Chen, Wen Chien Ting, Bo-Ying Bao, Ta-Yuan Chang, Hong-Zin Lee, Ying Pi Yang, Jiunn Bey Pao
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Oncology
Male
Colorectal cancer
Lymphovascular invasion
Epidemiology
Perineural invasion
lcsh:Medicine
Polymerase Chain Reaction
Gastrointestinal Cancers
lcsh:Science
Wnt Signaling Pathway
beta Catenin
Molecular Epidemiology
Multidisciplinary
biology
Cancer Risk Factors
Wnt signaling pathway
Colon Adenocarcinoma
DNA
Neoplasm
Middle Aged
Survival Rate
Genetic Epidemiology
Medicine
Female
Colorectal Neoplasms
Cancer Epidemiology
Research Article
medicine.medical_specialty
Beta-catenin
Adenomatous polyposis coli
Genetic Causes of Cancer
Adenomatous Polyposis Coli Protein
Single-nucleotide polymorphism
Gastroenterology and Hepatology
Polymorphism
Single Nucleotide
Internal medicine
Gastrointestinal Tumors
medicine
Biomarkers
Tumor
Humans
Neoplasm Invasiveness
Survival rate
Aged
Neoplasm Staging
lcsh:R
Cancers and Neoplasms
medicine.disease
Biomarker Epidemiology
Immunology
biology.protein
lcsh:Q
Follow-Up Studies
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 2, p e56196 (2013)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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