Association of common gene variants in the WNT/β-catenin pathway with colon cancer recurrence

D. Páez, A. Gerger, W. Zhang, D. Yang, M. J. LaBonte , L. Benhanim, M. Kahn, F. Lenz, C. Lenz, Y. Ning, T. Wakatsuki, F. Loupakis, H-J Lenz

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)142-50
Number of pages9
JournalThe pharmacogenomics journal
Volume14
Issue number2
Early online date02 Jul 2013
DOIs
Publication statusPublished - 01 Apr 2014

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Colonic Neoplasms
  • Ethnic Groups
  • Female
  • Fluorouracil
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Proportional Hazards Models
  • Wnt Proteins
  • Wnt Signaling Pathway

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