title: Predictive value of ERCC1 single-nucleotide polymorphism in patients receiving platinum-based chemotherapy for locally-advanced and advanced non-small cell lung cancer--a pilot study.
abstract: Platinum-based chemotherapy is the main type of I-line treatment of advanced and non-operative NSCLC patients without EGFR gene mutation. The excision repair cross-complementation group 1 (ERCC1) is an enzyme that executes the incision of the damaged DNA strand and removes platinum-induced DNA adducts. We investigated whether ERCC1 gene polymorphism has an effect on the response to chemotherapy and survival in 43 patients with NSCLC treated with platinum-based chemotherapy. ERCC1 19007 T&gt;C SNPs were assessed using a PCR-RFLP methods in DNA isolated from peripheral blood lymphocytes. Disease control occurred significantly (p = 0.045) more frequently in patients with CC or CT genotype compared to patients with TT genotype. Median PFS and OS for CC homozygous were 4 and 10.5 months, 4 and 12.5 months for CT heterozygous, but only 0.3 and 1.5 months for TT homozygous patients, respectively. The probability of PFS was significantly higher (HR = 0.438, 95% CI: 0.084-0.881, p = 0.03) and probability of OS was insignificantlyhigher (HR = 0.503, 95% CI: 0.129-1.137, p = 0.084) in patients with CC or CT genotype than in patients with TT genotype. Uncommon TT genotype of ERCC1 19007 T&gt;C polymorphism could predict poor response and shortening of progression free survival in NSCLC patients treated with platinum-based I-line chemotherapy. The analysis of this polymorphism may serve as a promising tool in the qualification of advanced NSCLC patients for appropriate chemotherapy.
authors.affiliation: Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Chodźki Str. 4a, 20-093 Lublin, Poland. krapa@poczta.onet.pl
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Kamila
authors.initials: K
authors.lastname: Wojas-Krawczyk
authors.forename: Radosław
authors.initials: R
authors.lastname: Mlak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kucharczyk
authors.forename: Beata
authors.initials: B
authors.lastname: Biernacka
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases