Camille Sibertin-Blanc1, Julien Mancini2, Aurélie Fabre3, Arnaud Lagarde3, Jean Del Grande4, Nicolas Levy3, Jean-François Seitz5, Sylviane Olschwang3, Laetitia Dahan5. 1. 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. 2. 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. 3. 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. 4. Department of Pathology, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France. 5. 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.
Abstract
BACKGROUND: No predictive marker has been yet identified for bevacizumab which is widely used in metastatic colorectal cancer. AIMS: 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.
BACKGROUND: No predictive marker has been yet identified for bevacizumab which is widely used in metastatic colorectal cancer. AIMS: 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.
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Authors: Andrés López-Cortés; César Paz-Y-Miño; Santiago Guerrero; Gabriela Jaramillo-Koupermann; Ángela León Cáceres; Dámaris P Intriago-Baldeón; Jennyfer M García-Cárdenas; Patricia Guevara-Ramírez; Isaac Armendáriz-Castillo; Paola E Leone; Luis Abel Quiñones; Juan Pablo Cayún; Néstor W Soria Journal: Pharmacogenomics J Date: 2019-10-15 Impact factor: 3.550
Authors: John M Mariadason; Niall C Tebbutt; Fiona Chionh; Val Gebski; Sheren J Al-Obaidi; Jennifer K Mooi; Maressa A Bruhn; Chee K Lee; Anderly C Chüeh; David S Williams; Andrew J Weickhardt; Kate Wilson; Andrew M Scott; John Simes; Jennifer E Hardingham; Timothy J Price Journal: Sci Rep Date: 2022-01-24 Impact factor: 4.379