Abstract
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.
Highlights
Lung cancer is a leading cause of cancer-related deaths in the developed countries
The aim of this study was the assessment of the relationship between 8 single nucleotide polymorphisms (SNPs) of 5 genes involved in nucleotide excision repair (NER) mechanism (ERCC1, XPA, XPC, XPD and XPG) and the effectiveness of cisplatin and gemcitabine based chemotherapy in patients with advanced Non-small cell lung cancer (NSCLC)
The genotypes of all the examined genes were in Hardy-Predictive Value of Single Nucleotide Polymorphisms of ERCC1, XPA, XPC, XPD and XPG Genes, Involved
Summary
Lung cancer is a leading cause of cancer-related deaths in the developed countries. In the world, more than 1.5 million new cases and deaths due to lung cancer are reported every year. Despite undeniable breakthrough related with the introduction of new molecularly targeted drugs, a substantial number of patients still receive cytostatics as a part of multidisciplinary treatment. Due to this fact, this type of therapy is addressed predominantly to patients diagnosed with adenocarcinoma, in whom the above mentioned rare molecular disorders occur more frequently [4, 5]. This type of therapy is addressed predominantly to patients diagnosed with adenocarcinoma, in whom the above mentioned rare molecular disorders occur more frequently [4, 5] It appears to be an interesting alternative to investigate new therapeutic targets and agents to maximize the benefits from the Bold^, well known, cytostatics
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