An exploratory association of polymorphisms in angiogenesis-related genes with susceptibility, clinical response and toxicity in gastrointestinal stromal tumors receiving sunitinib after imatinib failure
| العنوان: | An exploratory association of polymorphisms in angiogenesis-related genes with susceptibility, clinical response and toxicity in gastrointestinal stromal tumors receiving sunitinib after imatinib failure |
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| المؤلفون: | Milena Urbini, Guido Biasco, Maria Abbondanza Pantaleo, Vittorio Simeon, Nicola Venturoli, Giulia Sammarini, Gloria Ravegnini, Margherita Nannini, Corrado Zenesini, Patrizia Hrelia, Sabrina Angelini, Maristella Saponara, Lidia Gatto |
| المساهمون: | Ravegnini, G, Nannini, M, Zenesini, C, Simeon, V, Sammarini, G, Urbini, M, Gatto, L, Saponara, M, Biasco, G, Pantaleo, Ma, Venturoli, N, Hrelia, P, Angelini, S, Ravegnini, Gloria, Nannini, Margherita, Zenesini, Corrado, Simeon, Vittorio, Sammarini, Giulia, Urbini, Milena, Gatto, Lidia, Saponara, Maristella, Biasco, Guido, Pantaleo, Maria A, Venturoli, Nicola, Hrelia, Patrizia, Angelini, Sabrina |
| المصدر: | Angiogenesis. 20:139-148 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Oncology, Cancer Research, Candidate gene, Indoles, Time Factors, Physiology, Angiogenesis, Clinical Biochemistry, Kaplan-Meier Estimate, Pharmacology, Metastasis, 0302 clinical medicine, VEGF pathway, Sunitinib, Treatment Failure, Aged, 80 and over, Neovascularization, Pathologic, GiST, Clinical outcome, Pharmacogenetic, OS, Middle Aged, Angiogenesi, VEGFR2, VEGFR1, 030220 oncology & carcinogenesis, Toxicity, Disease Progression, Imatinib Mesylate, Female, VEGFR3, GIST, medicine.drug, VEGFA, Adult, medicine.medical_specialty, TTP, Gastrointestinal Stromal Tumors, SNP, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Pyrroles, Polymorphism, Genetic Association Studies, Aged, Demography, Vascular Endothelial Growth Factor Receptor-1, business.industry, Vascular Endothelial Growth Factor Receptor-3, medicine.disease, 030104 developmental biology, Haplotypes, Multivariate Analysis, Clinical response, business, Pharmacogenetics |
| الوصف: | The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and metastasis. The most important actors in the angiogenic pathway are VEGFA and its receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we hypothesized that germline variants may affect sunitinib efficacy (TTP and OS) and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in 54 GIST patients, treated with second-line sunitinib and 147 healthy controls. Through a multiple candidate gene approach, we also investigated, for the first time, any possible significant associations with GIST susceptibility and clinical pathological features. The most important result shows two associations between polymorphisms in VEGFR3 rs6877011 (CC vs. CG, OR 9.7, 95% CI 3.31-28.4; P < 0.001) and rs7709359 (AA+AG vs. GG, OR 5.01, 95% CI 1.33-18.8; P = 0.017) and TTP. Interestingly, the association between VEGFR3 rs6877011 and TTP maintained the significance after applying the Bonferroni correction for multiple testing (P = 0.017). We also highlighted the association with sunitinib-related toxicity; in particular, VEGFA polymorphism rs3025039 (CT+TT vs. CC, OR 15.3, 95% CI 2.2-102.1; P = 0.005) is associated with severe toxicity, with the presence of the variant T allele associated with a grade a 3 AE. Because of the small sample size and large number of tests performed, we cannot ignore the possibility that some associations have been retrieved by chance. However, the influence of VEGF polymorphisms in angiogenesis is a hypothesis worthy of exploration in cellular models and confirmation in a sizeable cohort of patients. |
| وصف الملف: | ELETTRONICO |
| تدمد: | 1573-7209 0969-6970 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b20b04e168634d2152792979a8d9a9be https://doi.org/10.1007/s10456-016-9534-5 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....b20b04e168634d2152792979a8d9a9be |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15737209 09696970 |
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