Germline polymorphisms in genes involved in the CD44 signaling pathway are associated with clinical outcome in localized gastric adenocarcinoma Journal Article


Authors: Winder, T.; Ning, Y.; Yang, D.; Zhang, W.; Power, D. G.; Bohanes, P.; Gerger, A.; Wilson, P. M.; Lurje, G.; Tang, L. H.; Shah, M.; Lenz, H. J.
Article Title: Germline polymorphisms in genes involved in the CD44 signaling pathway are associated with clinical outcome in localized gastric adenocarcinoma
Abstract: The cluster of differentiation 44 (CD44) signaling pathway is crucial in cancer-cell growth, invasion, proliferation and metastasis. CD44 is a transmembrane receptor for hyaluronan and osteopontin, and has recently attracted attention as a gastric cancer stem cell marker. Previous studies showed that polymorphisms in the CD44 gene can influence both human cancer survival and determine cellular response to cytotoxic chemotherapeutics. In addition, CD44 protein overexpression has been associated with poor prognosis in gastric adenocarcinoma (GA). We tested the hypothesis whether polymorphisms involved in the CD44 pathway will predict clinical outcome in patients with localized GA. Either blood or formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 137 patients with localized GA at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was isolated and polymorphisms within the CD44 pathway were determined by PCR-RFLP technique. In univariate analysis CD44 rs187116 and CD44 rs7116432 were significantly associated with time to tumor recurrence (TTR) and overall survival (OS). After adjusting for covariates, patients harboring at least one G allele of CD44 rs187116 remained significantly associated with TTR (adjusted p = 0.009) and OS (adjusted p = 0.045). Further, patients harboring CD44 T-A haplotype were at the lowest risk of developing tumor recurrence (HR: 0.255; 95% CI: 0.11-0.591; adjusted p = 0.001) and death (HR 0.198; 95% CI: 0.07-0.563; adjusted p = 0.002). These results provide the first evidence that CD44 polymorphisms predict clinical outcome in patients with localized GA. This may help to identify localized GA patients at high risk for tumor recurrence. Copyright © 2011 UICC.
Keywords: signal transduction; adult; cancer survival; controlled study; human cell; major clinical study; cisplatin; fluorouracil; united states; cancer patient; outcome assessment; allele; gene; gene expression; genetic association; haplotype; irinotecan; germ line; tumor recurrence; folinic acid; outcome; hyaluronic acid; oxaliplatin; hermes antigen; stomach adenocarcinoma; dna polymorphism; gastric adenocarcinoma; dna isolation; osteopontin; polymorphisms; cd44; cd44 gene
Journal Title: International Journal of Cancer
Volume: 129
Issue: 5
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 2011-09-01
Start Page: 1096
End Page: 1104
Language: English
DOI: 10.1002/ijc.25787
PROVIDER: scopus
PMCID: PMC3139396
PUBMED: 21105049
DOI/URL:
Notes: --- - "Export Date: 17 August 2011" - "CODEN: IJCNA" - "Source: Scopus"
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MSK Authors
  1. Derek Gerard Power
    37 Power
  2. Manish Shah
    174 Shah
  3. Laura Hong Tang
    320 Tang