title: A possible association of baseline serum IL-17A concentrations with progression-free survival of metastatic colorectal cancer patients treated with a bevacizumab-based regimen.
abstract: Colorectal cancer is a major public health issue worldwide. Interleukin-17 (IL-17) and Th17 (T-helper cell type 17)-related molecules are involved in tumor development and in resistance to bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody used in association with chemotherapy in metastatic colorectal cancer. Some studies have previously shown that IL-17A and IL-17F polymorphisms, respectively rs2275913 and rs763780, are associated with gastric or colorectal cancer risk. Here we aimed at studying the influence of IL-17A-related individual factors on overall survival and progression-free survival in patients with metastatic colorectal cancer treated with a bevacizumab-based chemotherapy.
  
  
  
  Pre-treatment serum biomarkers were retrospectively evaluated in 122 metastatic colorectal cancer patients treated by bevacizumab in combination with chemotherapy at 2-weeks intervals in a prospective cohort study (NCT00489697). The polymorphisms of IL-17A and IL-17F were analyzed by polymerase chain reaction - restriction fragment length polymorphism. Serum concentrations of Th17-related cytokines were measured by MultiPlex. The impact of individual parameters on overall survival and progression-free survival was assessed using multivariate Cox models.
  
  
  
  High baseline IL-17A serum concentrations were significantly associated with shorter progression-free survival [p = 0.043]. Other baseline serum Th17-related cytokines and polymorphisms of IL-17 were not associated with overall survival or progression-free survival.
  
  
  
  In this ancillary study, baseline serum IL-17A concentration is the only Th17/IL-17 related factor that was significantly associated with the response of patients with metastatic colorectal cancer to bevacizumab. But this main significant result is highly dependent on one case which, if left out, weakens the data. Other clinical studies are required to confirm this association.
  
  
  
  NCT00489697 . June 20, 2007.
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lereclus
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.
authors.forename: Mira
authors.initials: M
authors.lastname: Tout
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Girault
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Baroukh
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.|CHRU de Tours, Department of Hepato-Gastroenterology and Digestive Oncology, Tours, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Caulet
authors.affiliation: INSERM, UMR 1098, Department of Medical Oncology, University Hospital, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Department of Hepato-Gastroenterology and Digestive Oncology, University Hospital Robert Debré, Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.|CHRU de Tours, Laboratory of Pharmacology-Toxicology, Tours, France.
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.|CHRU de Tours, Laboratory of Pharmacology-Toxicology, Tours, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France.|CHRU de Tours, Department of Hepato-Gastroenterology and Digestive Oncology, Tours, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lecomte
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, UFR de médecine, BP 3223, 10, boulevard Tonnellé, 37032, Tours Cedex 01, France. william.raoul@univ-tours.fr.
authors.forename: William
authors.initials: W
authors.lastname: Raoul
mesh_terms: D000368:Aged; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D000068258:Bevacizumab
keywords: Bevacizumab; IL-17 polymorphisms; Metastatic colorectal cancer; Survival analysis: score; Th17-related cytokines; Vascular endothelial growth factor