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

• DOI: 10.1007/s12253-018-0459-8
• Publication Date: 2018-07-31T05:29:20Z
• Authors: Radosław Mlak; Paweł Krawczyk; Iwona Homa-Mlak; Tomasz Powrózek; Marzanna Ciesielka; Piotr Kozioł; Janusz Milanowski; Teresa Małecka-Ma...
• Keywords: Adult; Male; 0301 basic medicine; Lung Neoplasms; Nuclear Proteins; Adenocarcinoma; Middle Aged; Endonucleases; Prognosis; Deoxycytidine; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Large Cell; Humans; Original Article; Female; Cisplatin; Aged; Follow-Up Studies

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.