Predictive Value of Single Nucleotide Polymorphisms of ERCC1, XPA, XPC, XPD and XPG Genes, Involved in NER Mechanism in Patients with Advanced NSCLC Treated with Cisplatin and Gemcitabine

Autor: Tomasz Powrózek, Marzanna Ciesielka, Teresa Małecka-Massalska, Paweł Krawczyk, Radosław Mlak, Janusz Milanowski, Piotr Kozioł, Iwona Homa-Mlak
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Cancer Research
Lung Neoplasms
medicine.medical_treatment
Deoxycytidine
0302 clinical medicine
Non-small cell lung cancer
Carcinoma
Non-Small-Cell Lung
Genotype
Antineoplastic Combined Chemotherapy Protocols
Medicine
Nuclear Proteins
General Medicine
Middle Aged
Prognosis
Xeroderma Pigmentosum Group A Protein
DNA-Binding Proteins
Survival Rate
Oncology
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
Female
Original Article
medicine.drug
Adult
DNA repair
Single-nucleotide polymorphism
Adenocarcinoma
Pathology and Forensic Medicine
03 medical and health sciences
Biomarkers
Tumor
Humans
Polymorphism
Aged
Xeroderma Pigmentosum Group D Protein
Cisplatin
Chemotherapy
business.industry
XPD
chemotherapy
Endonucleases
Gemcitabine
030104 developmental biology
Cancer research
ERCC2
Carcinoma
Large Cell
ERCC1
business
Nucleotide excision repair
Follow-Up Studies
Transcription Factors
Zdroj: Pathology Oncology Research
ISSN: 1532-2807
Popis: The combination of cisplatin and gemcitabine is still one of the most frequently used first-line chemotherapy scheme in patients with advanced non-small cell lung cancer (NSCLC), in which tyrosine kinase inhibitors (TKIs) cannot be administered. Unfortunately, more than half of the patients have no benefit from chemotherapy but are still exposed to its toxic effects. Therefore, single nucleotide polymorphisms (SNPs) in the genes involved in nucleotide excision repair (NER) mechanism may be a potential predictive factor of efficiency of cytostatic based chemotherapy. The aim of the study was to evaluate the correlation between SNPs of the genes involved in NER mechanism and the effectiveness of chemotherapy based on cisplatin and gemcitabine in patients with advanced NSCLC. The study group included 91 NSCLC patients treated with first-line chemotherapy using cisplatin and gemcitabine. Genotyping was carried out using a mini-sequencing technique (SNaPshot™ PCR). The median progression-free survival (PFS) was significantly shorter in carriers of CC genotype of the XPD/ERCC2 (2251A > C) gene compared to patients with AA/AC genotypes (2 vs. 4.5 months; p = 0.0444; HR = 3.19, 95%CI:1.03–9.91). Rare CC genotype of XPD/ERCC2 gene, may be considered as an unfavorable predictive factor for chemotherapy based on cisplatin and gemcitabine in patients with advanced NSCLC.
Databáze: OpenAIRE
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