Identification of polymorphic variants associated with erlotinib-related skin toxicity in advanced non-small cell lung cancer patients by DMET microarray analysis

Autor: 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
Přispěvatelé: 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.
Jazyk: angličtina
Rok vydání: 2016
Předmět:
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
Zdroj: 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
DOI: 10.1007/s00280-015-2916-3
Popis: 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.
Databáze: OpenAIRE
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