title: Genetic variations in angiogenesis pathway genes associated with clinical outcome in localized gastric adenocarcinoma.
abstract: BACKGROUND
  Angiogenesis has been attributed to be a well-recognized aspect of human cancer biology. As such, proteinase-activated receptor (PAR)-1, endostatin (ES) and interleukin-8 (IL-8) mediate the regulation of early-onset angiogenesis and in turn impact the process of tumor-growth and disease progression.
  
  
  METHODS
  Formalin-fixed paraffin-embedded tissues were obtained from 137 patients with localized gastric cancer at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was extracted and genotyping was carried out using PCR-restriction fragment length polymorphism-based protocols.
  
  
  RESULTS
  In false discovery rate-adjusted univariate analysis, PAR-1 -506 ins/del (P < 0.001), ES +4349 G>A (P = 0.004), and IL-8 -251 T>A (P < 0.0001) were associated with time to tumor recurrence (TTR). Further, PAR-1 -506 ins/del and IL-8 -251 were associated with overall survival (OS). After adjusting for covariates, IL-8 remained significantly associated with TTR (adjusted P = 0.003) and OS (adjusted P = 0.049), whereas ES was significantly associated with TTR (adjusted P = 0.026).
  
  
  CONCLUSIONS
  Polymorphisms in PAR-1, ES, and IL-8 may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinoma. The assessment of the patients' individual risk on the basis of interindividual genotypes may therefore help to identify patient subgroups at high risk for poor clinical outcome.
authors.affiliation: Division of Medical Oncology, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Lurje
authors.forename: H
authors.initials: H
authors.lastname: Husain
authors.forename: D G
authors.initials: DG
authors.lastname: Power
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Groshen
authors.forename: A
authors.initials: A
authors.lastname: Pohl
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.forename: P C
authors.initials: PC
authors.lastname: Manegold
authors.forename: A
authors.initials: A
authors.lastname: El-Khoueiry
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.forename: L H
authors.initials: LH
authors.lastname: Tang
authors.forename: M A
authors.initials: MA
authors.lastname: Shah
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D043169:Endostatins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D044463:Receptor, PAR-1 / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D043169:Endostatins; D016209:Interleukin-8; D044463:Receptor, PAR-1