11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose:

          The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF–associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC).

          Patients and methods:

          Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study. Patients receiving treatment with FOLFIRI and cetuximab (FIRE-3, n = 204) served as a negative control. 12 SNPs in eight autophagy-related genes (ATG3/5/8/13, beclin 1, FIP200, unc-51-like kinase 1, UVRAG) were analysed by PCR-based direct sequencing.

          Results:

          The FIP200 rs1129660 variant showed significant associations with hypertension in the TRIBE cohort. Patients harbouring any G allele of the FIP200 rs1129660 SNP showed a significantly lower rate of grade 2–3 hypertension compared with the A/A genotype (3% versus 15%, odds ratio [OR] 0.17; 95% confidence interval [CI], 0.02–0.73; P = 0.009). Similarly, G allele carriers of the FIP200 rs1129660 SNP were less likely to develop grade 2–3 hypertension than patients with an A/A genotype in the FIRE-3 validation cohort (9% versus 20%, OR 0.43; 95% CI, 0.14–1.11; P = 0.077), whereas this association could not be observed in the control cohort (12% versus 9%, OR 1.40; 95% CI, 0.45–4.04; P = 0.60).

          Conclusion:

          This is the first report demonstrating that polymorphisms in the autophagy-related FIP200 gene may predict hypertension in patients with mCRC treated with FOLFIRI and bevacizumab.

          Related collections

          Author and article information

          Journal
          9005373
          1697
          Eur J Cancer
          Eur. J. Cancer
          European journal of cancer (Oxford, England : 1990)
          0959-8049
          1879-0852
          13 September 2020
          26 March 2017
          May 2017
          17 September 2020
          : 77
          : 13-20
          Affiliations
          [a ]Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
          [b ]Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
          [c ]Department of Medical Oncology and Comprehensive Cancer Center, University of Munich (LMU), Marchioninistrasse 15, 81377 Munich, Germany
          [d ]Oncologia Medica 1, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Gattamelata 64, 35128 Padova, Italy
          [e ]U.O. Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Roma 67, 56126 Pisa, Italy
          Author notes
          [* ] Corresponding author: Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. Fax: +1 323 865 0061. lenz@ 123456med.usc.edu (H.-J. Lenz).
          Article
          PMC7497847 PMC7497847 7497847 nihpa1623157
          10.1016/j.ejca.2017.02.020
          7497847
          28347919
          39c73491-1910-419e-a49d-611505d1e81f
          History
          Categories
          Article

          Bevacizumab-associated toxicity,Hypertension,Colorectal cancer,Autophagy,Single-nucleotide polymorphism,FOLFIRI/bevacizumab

          Comments

          Comment on this article