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Article

Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer

1
Department of Health Sciences, Health Sciences Faculty, European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain
2
Department of Medicine, Health Sciences Faculty, Universidad Europea de Madrid, Villaviciosa de Odón, 28670 Madrid, Spain
3
Department of Oncology, University Hospital of Fuenlabrada, Fuenlabrada, 28942 Madrid, Spain
4
Department of Pathological Anatomy, University Hospital of Fuenlabrada, Fuenlabrada, 28942 Madrid, Spain
5
Department of Pre-Clinical Dentistry, Health Sciences Faculty, Universidad Europea de Madrid, Villaviciosa de Odón, 28670 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Donato Gemmati
Int. J. Mol. Sci. 2021, 22(3), 1381; https://doi.org/10.3390/ijms22031381
Received: 7 January 2021 / Revised: 25 January 2021 / Accepted: 26 January 2021 / Published: 30 January 2021
(This article belongs to the Special Issue Gender Medicine: Pharmacogenetics and Personalised Medicine 2.0)
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: 1.52–7.14; 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. View Full-Text
Keywords: bevacizumab; colorectal cancer; angiogenesis; polymorphisms bevacizumab; colorectal cancer; angiogenesis; polymorphisms
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MDPI and ACS Style

Gaibar, M.; Galán, M.; Romero-Lorca, A.; Antón, B.; Malón, D.; Moreno, A.; Fernández-Santander, A.; Novillo, A. Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer. Int. J. Mol. Sci. 2021, 22, 1381. https://doi.org/10.3390/ijms22031381

AMA Style

Gaibar M, Galán M, Romero-Lorca A, Antón B, Malón D, Moreno A, Fernández-Santander A, Novillo A. Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer. International Journal of Molecular Sciences. 2021; 22(3):1381. https://doi.org/10.3390/ijms22031381

Chicago/Turabian Style

Gaibar, María, Miguel Galán, Alicia Romero-Lorca, Beatriz Antón, Diego Malón, Amalia Moreno, Ana Fernández-Santander, and Apolonia Novillo. 2021. "Genetic Variants of ANGPT1, CD39, FGF2 and MMP9 Linked to Clinical Outcome of Bevacizumab Plus Chemotherapy for Metastatic Colorectal Cancer" International Journal of Molecular Sciences 22, no. 3: 1381. https://doi.org/10.3390/ijms22031381

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