title: Vascular Endothelial Growth Factor A c.*237C>T polymorphism is associated with bevacizumab efficacy and related hypertension in metastatic colorectal cancer.
abstract: BACKGROUND
  No predictive marker has been yet identified for bevacizumab which is widely used in metastatic colorectal cancer.
  
  
  OBJECTIVE
  Evaluate impact of single nucleotide polymorphisms involved in Vascular Endothelial Growth Factor pathway on efficacy and tolerance of bevacizumab.
  
  
  METHODS
  We retrospectively included patients who were treated with bevacizumab-based chemotherapy for metastatic colorectal cancer, and for whom a deoxyribonucleic acid sample was available. Ten polymorphisms in Vascular Endothelial Growth Factor-A, his receptors and hypoxia inducible factor-1α were genotyped on germ line DNA using real-time polymerase chain reaction TaqMan(®).
  
  
  RESULTS
  89 patients were included. The CC genotype for rs3025039 (Vascular Endothelial Growth Factor-A c.*237C>T) was associated with a significantly better time to treatment failure (14.2 months) as compared to the CT and TT genotypes (6.0 months) in univariate (p = 0.004) and multivariate (p = 0.022; HR = 0.57; 95% CI [0.35-0.92]) analysis. Patients with at least one T allele showed worse overall survival and progression-free survival as compared to homozygous CC patients in univariate analysis (respectively p = 0.016 and p = 0.044). There was significantly more severe hypertension for the CC genotype (29.5%) compared to CT and TT genotypes (7.1%) (p = 0.022) in multivariate analysis.
  
  
  CONCLUSIONS
  In this retrospective study, the rs3025039 polymorphism was significantly associated with time to treatment failure and hypertension in patients treated with bevacizumab-based chemotherapy.
authors.affiliation: Department of Digestive Oncology, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France. Electronic address: camille.sibertin-blanc@ap-hm.fr.
authors.forename: Camille
authors.initials: C
authors.lastname: Sibertin-Blanc
authors.affiliation: Department of Biostatistics, Assistance Publique Hôpitaux de Marseille, Marseille, France; UMR_S912, Economic & Social Sciences, Health Systems & Medical Informatics, SESSTIM, Aix Marseille Université, Inserm, IRD, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.affiliation: UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France; Department of Medical Genetics, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Fabre
authors.affiliation: UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France; Department of Medical Genetics, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lagarde
authors.affiliation: Department of Pathology, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Del Grande
authors.affiliation: UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France; Department of Medical Genetics, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levy
authors.affiliation: Department of Digestive Oncology, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.affiliation: UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France; Department of Medical Genetics, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.affiliation: Department of Digestive Oncology, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dahan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics / Q000556:secondary*; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005602:France; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D004273:DNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Bevacizumab; Colorectal cancer; Polymorphism