title: Genetic variations in the VEGF pathway as prognostic factors in metastatic colorectal cancer patients treated with oxaliplatin-based chemotherapy.
abstract: Angiogenesis is a significant biological mechanism in the progression and metastasis of solid tumors. Vascular endothelial growth factor (VEGF), its receptors and signaling effectors have a central role in tumor-induced angiogenesis. Genetic variation in the VEGF pathway may impact on tumor angiogenesis and, hence, on clinical cancer outcomes. This study evaluates the influence of common genetic variations within the VEGF pathway in the clinical outcomes of 172 metastatic colorectal cancer (mCRC) patients treated with first-line oxaliplatin/5-fluorouracil chemotherapy. A total of 27 single-nucleotide polymorphisms (SNPs) in 16 genes in the VEGF-dependent angionenesis process were genotyped using a dynamic array on the BioMark™ system. After assessing the KRAS mutational status, we found that four SNPs located in three genes (KISS1, KRAS and VEGFR2) were associated with progression-free survival. Five SNPs in three genes (ITGAV, KRAS and VEGFR2) correlated with overall survival. The gene-gene interactions identified in the survival tree analysis support the importance of VEGFR2 rs2071559 and KISS1 rs71745629 in modulating these outcomes. This study provides evidence that functional germline polymorphisms in the VEGF pathway may help to predict outcome in mCRC patients who undergo oxaliplatin/5-fluorouracil chemotherapy.
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Unit of Biomarkers and Susceptibility, IDIBELL-Catalan Institute of Oncology, Gran Via de l'Hospitalet, Barcelona, Spain.|CIBERESP, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Paré-Brunet
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Pare Claret, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sebio
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERER U-705, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Unit of Biomarkers and Susceptibility, IDIBELL-Catalan Institute of Oncology, Gran Via de l'Hospitalet, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Berenguer-Llergo
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERER U-705, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Río
authors.affiliation: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Pare Claret, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Barnadas
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|CIBERER U-705, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Baiget
authors.affiliation: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Pare Claret, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Páez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D056726:Genetic Association Studies; D006801:Humans; D059648:Kisspeptins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D009944:Organoplatinum Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D005472:Fluorouracil