1. Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer
- Author
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María Gaibar, Beatriz Antón, Miguel Galán, Apolonia Novillo, Ana Fernández-Santander, Alicia Romero-Lorca, Amalia Moreno, Diego Malón, Servicio de Oncología. Hospital Universitario de Fuenlabrada, and Servicio de Anatomía Patológica. Hospital Universitario de Fuenlabrada
- Subjects
0301 basic medicine ,Oncology ,Male ,Angiogenesis ,Colorectal cancer ,medicine.medical_treatment ,Biopsy ,Angiogenesis Inhibitors ,lcsh:Chemistry ,angiogenesis ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,Neovascularization, Pathologic ,Apyrase ,General Medicine ,Middle Aged ,Cáncer ,Progression-Free Survival ,Computer Science Applications ,Bevacizumab ,Matrix Metalloproteinase 9 ,030220 oncology & carcinogenesis ,Female ,Fibroblast Growth Factor 2 ,Colorectal Neoplasms ,medicine.drug ,Adult ,medicine.medical_specialty ,Farmacología ,Single-nucleotide polymorphism ,colorectal cancer ,Neovascularización patológica ,bevacizumab ,Polymorphism, Single Nucleotide ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Internal medicine ,Angiopoietin-1 ,Biomarkers, Tumor ,Neoplasias Colorrectales ,Humans ,Neoplasias del colon ,Progression-free survival ,Genetic variability ,Physical and Theoretical Chemistry ,Allele ,Molecular Biology ,Aged ,Retrospective Studies ,Chemotherapy ,Inhibidores de la Angiogénesis ,business.industry ,Organic Chemistry ,medicine.disease ,Genética ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Drug Resistance, Neoplasm ,business ,polymorphisms - Abstract
Angiogenesis pathway genes show substantial genetic variability causing inter-individual differences in responses to anti-angiogenic drugs. We examined 20 single nucleotide polymorphisms (SNPs) in 13 of these genes to predict tumour response and clinical outcome measured as progression free survival (PFS) and overall survival (OS) in 57 patients with metastatic colorectal cancer (mCRC) given bevacizumab plus chemotherapy. SNPs were detected (iPLEX®, Assay) in genomic DNA extracted from formalin-fixed paraffin-embedded tumour specimens. The variant allele CD39 rs11188513 was associated with a good tumour response (p = 0.024). Patients homozygous for the wild-type allele FGF2 rs1960669 showed a median PFS of 10.95 months versus 5.44 months for those with at least one variant allele-A (HR 3.30, 95% CI: 1.52&ndash, 7.14, p = 0.001). Patients homozygous for wild-type MMP9 rs2236416 and rs2274755 showed a median PFS of 9.48 months versus 6 and 6.62 months, respectively, for those with at least one variant allele (p = 0.022, p = 0.043, respectively). OS was also lengthened to 30.92 months (p = 0.034) in carriers of wild-type ANGPT1 rs2445365 versus 22.07 months for those carrying at least one variant allele-A. These gene variants were able to predict clinical outcome and tumour response in mCRC patients given bevacizumab-based therapy.
- Published
- 2021
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