Identification of polymorphic variants associated with erlotinib-related skin toxicity in advanced non-small cell lung cancer patients by DMET microarray analysis
| العنوان: | Identification of polymorphic variants associated with erlotinib-related skin toxicity in advanced non-small cell lung cancer patients by DMET microarray analysis |
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| المؤلفون: | Vito Barbieri, Serafino Conforti, Eleonora Iuliano, Pierosandro Tagliaferri, Maria Teresa Di Martino, Cirino Botta, Francesca Scionti, Pietro Hiram Guzzi, Mariamena Arbitrio, Mario Cannataro, Stefania Codispoti, Pierfrancesco Tassone, Emanuela Altomare, Giuseppe Agapito |
| المساهمون: | Arbitrio M., Di Martino M.T., Barbieri V., Agapito G., Guzzi P.H., Botta C., Iuliano E., Scionti F., Altomare E., Codispoti S., Conforti S., Cannataro M., Tassone P., Tagliaferri P. |
| المصدر: | Cancer chemotherapy and pharmacology 77 (2016): 205–209. doi:10.1007/s00280-015-2916-3 info:cnr-pdr/source/autori:Arbitrio M.; Di Martino M.T.; Barbieri V.; Agapito G.; Guzzi P.H.; Botta C.; Iuliano E.; Scionti F.; Altomare E.; Codispoti S.; Conforti S.; Cannataro M.; Tassone P.; Tagliaferri P./titolo:Identification of polymorphic variants associated with erlotinib-related skin toxicity in advanced non-small cell lung cancer patients by DMET microarray analysis/doi:10.1007%2Fs00280-015-2916-3/rivista:Cancer chemotherapy and pharmacology/anno:2016/pagina_da:205/pagina_a:209/intervallo_pagine:205–209/volume:77 |
| بيانات النشر: | Springer Verlag, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, Cancer Research, Lung Neoplasms, genetic structures, Microarray, Pharmacology, Toxicology, Skin rash, 0302 clinical medicine, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, Genotype, Pharmacology (medical), Erlotinib Hydrochloride, Cholecalciferol, Oligonucleotide Array Sequence Analysis, Middle Aged, Erlotinib, 030220 oncology & carcinogenesis, Female, Drug Eruptions, medicine.drug, medicine.medical_specialty, Single-nucleotide polymorphism, Antineoplastic Agents, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, medicine, Humans, Lung cancer, Aged, Retrospective Studies, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Inflammation, business.industry, Microarray analysis techniques, Cancer, Single nucleotide polymorphisms, medicine.disease, Single nucleotide polymorphism, 030104 developmental biology, DMET, Quality of Life, business |
| الوصف: | Purpose: Erlotinib is a targeted agent commonly used in advanced non-small cell lung cancer (aNSCLC). However, drug-related skin toxicity often may affect the quality of life of cancer patients and lead to treatment discontinuation. Genetic polymorphisms in drug transporters and metabolizing enzymes play a major role in the interindividual variability in terms of efficacy and toxicity of erlotinib treatment. The aim of our study was to identify genetic determinants in adsorption, distribution, metabolism, and excretion genes influencing skin rash (SR) by the novel drug-metabolizing enzyme and transporter (DMET) microarray Affymetrix platform in aNSCLC patients. Methods: In a retrospective study, 34 erlotinib-treated aNSCLC patients were genotyped by DMET Plus chip: 23 patients experienced SR (cases), while 11 patients did not (controls). Peripheral blood DNA was genotyped. Genotype association was analyzed by Fisher's exact test, and the toxicity-associated gene sets underwent Ingenuity Pathway Analysis (IPA)®. Results: Seven SNPs in six genes (CYP27B1, MAT1A1, CHST1, CYP4B1, ADH6, and SLC22A1) were associated with the occurrence of SR or with a protective effect. Specifically, the rs8176345 in CYP27B1 gene was significantly correlated with SR (p = 0.0003, OR 55.55, 95 % CI 2.7036-1141.1707). The IPA on SR-related genes highlighted the role of a variety of canonical pathways including 1,25-dihydroxyvitamin D3 biosynthesis, S-adenosyl-l-methionine biosynthesis, and methionine degradation I (to homocysteine) in SR development. Conclusion: Although exploratory, this study indicates rs8176345 in CYP27B1 gene as significantly correlated with erlotinib-induced SR in aNSCLC patients probably through a mechanism mediated by vitamin D3 and inflammation at skin level. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::017f396d53dbb9950317309f01f1b753Test http://hdl.handle.net/10447/512516Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....017f396d53dbb9950317309f01f1b753 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |