Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Páez, D; Gerger, A; Zhang, W; Yang, D; Labonte, MJ; Benhanim, L; Kahn, M; Lenz, F; Lenz, C; Ning, Y; Wakatsuki, T; Loupakis, F; Lenz, HJ.
Association of common gene variants in the WNT/β-catenin pathway with colon cancer recurrence.
Pharmacogenomics J. 2014; 14(2):142-150
Doi: 10.1038/tpj.2013.20
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Gerger Armin
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- Abstract:
- Wnt/β-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Alleles -
- Colonic Neoplasms - drug therapy
- Colonic Neoplasms - genetics
- Colonic Neoplasms - pathology
- Ethnic Groups - genetics
- Female -
- Fluorouracil - administration & dosage
- Humans -
- Male -
- Middle Aged -
- Neoplasm Recurrence, Local - genetics
- Neoplasm Recurrence, Local - pathology
- Neoplasm Staging -
- Polymorphism, Single Nucleotide -
- Prognosis -
- Proportional Hazards Models -
- Wnt Proteins - genetics
- Wnt Signaling Pathway - genetics
- Find related publications in this database (Keywords)
- colon cancer
- polymorphisms
- WNT