Trial reportEuropean journal of cancer (Oxford, England : 1990)2017
Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.
Trial report in European journal of cancer (Oxford, England : 1990), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 31 citations in OpenAlex.
- VEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer.Scientific reports · 2022Trial
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- Autophagy in doxorubicin resistance: basic concepts, therapeutic perspectives and clinical translation.Frontiers in immunology · 2025Review
- Safety of first-line systemic therapy in patients with metastatic colorectal cancer: a network meta-analysis of randomized controlled trials.BMC cancer · 2024Article
- Patterns and trends of mortality from metastatic colorectal cancer in Shanghai, China from 2005 to 2021: a population-based retrospective analysis.Journal of cancer research and clinical oncology · 2024Article
- Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC.Pharmaceutics · 2022Review
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- Genetic variants in autophagy-related geneFrontiers in oncology · 2022Article
- Article
- Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes.International journal of molecular sciences · 2020Review
- Pharmacogenetics for severe adverse drug reactions induced by molecular-targeted therapy.Cancer science · 2020Review
- Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.Frontiers in pharmacology · 2020Review
- Identification of a Genomic Region betweenClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers.British journal of cancer · 2018Article
- Bevacizumab-induced hypertension: Clinical presentation and molecular understanding.Pharmacology & therapeutics · 2018Review
- Clinical Implications of the Autophagy Core Gene Variations in Advanced Lung Adenocarcinoma Treated with Gefitinib.Scientific reports · 2017Article
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeThe 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
methodsPatients 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.
resultsThe 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).
conclusionThis 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.
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