title: Association of CD133 polymorphisms and response to bevacizumab in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy.
  
  
  OBJECTIVE
  The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment.
  
  
  METHODS
  Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP.
  
  
  RESULTS
  No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002).
  
  
  CONCLUSIONS
  The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.
authors.affiliation: Third Department of Medical Oncology, General Oncology Hospital of Kifissia ``AgioiAnargyroi'', Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Aravantinos
authors.affiliation: Third Department of Medical Oncology, General Oncology Hospital of Kifissia ``AgioiAnargyroi'', Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Isaakidou
authors.affiliation: First Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Karantanos
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Sioziou
authors.affiliation: First Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece.
authors.forename: G E
authors.initials: GE
authors.lastname: Theodoropoulos
authors.affiliation: Second Department of Internal Medicine, School of Medicine, University of Athens, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Pektasides
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Gazouli
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D000068258:Bevacizumab; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin
keywords: CD133 polymorphisms; Colorectal cancer; bevacizumab