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Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients.
- Subjects :
- Male
0301 basic medicine
Oncology
Lung Neoplasms
medicine.medical_treatment
Pharmacology
Tyrosine-kinase inhibitor
Targeted therapy
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
Crown Ethers
Medicine
Epidermal growth factor receptor
Erlotinib Hydrochloride
Aged, 80 and over
Multidisciplinary
biology
Gefitinib
Middle Aged
ErbB Receptors
Treatment Outcome
030220 oncology & carcinogenesis
Female
Erlotinib
medicine.drug
Adult
China
medicine.medical_specialty
ATP Binding Cassette Transporter, Subfamily B
medicine.drug_class
Antineoplastic Agents
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
Asian People
Internal medicine
Icotinib Hydrochloride
Humans
Lung cancer
Protein Kinase Inhibitors
Aged
business.industry
Proteins
medicine.disease
respiratory tract diseases
030104 developmental biology
Quinazolines
biology.protein
business
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....61dbcadc2f65f68518b0ac254e6bddb4