A C118T polymorphism of ERCC1 and response to cisplatin chemotherapy in patients with late-stage non-small cell lung cancer

Abstract

Purpose: To investigate the association between a single-nucleotide polymorphism (SNP) of ERCC1, Asn118Asn (C → T), and the response of patients with late-stage non-small cell lung cancer (NSCLC) (n = 142) to cisplatin-based chemotherapy.

Methods: The SNP, Asn118Asn (C → T), in codon 118 of ERCC1 was detected using an AllGlo™ Probe-based real-time PCR kit. The short-term clinical outcomes were evaluated by measuring complete and partial responses (CR and PR), whereas progression-free survival (PFS) and overall survival (OS) were determined to indicate long-term outcomes.

Results: The allelic frequencies of the ERCC1 codon 118 were found to be 60.6% (C/C), 33.1% (C/T), and 6.3% (T/T), respectively. Overall, the CR and PR to cisplatin-based treatment were 33.1%. Notably, the response rate of patients carrying an ERCC1 118 C/C allele was more than twofold higher than that of patients with a C/T or T/T genotype (95% confidence interval (CI), 1.065-3.910, P = 0.032). Correspondingly, the long-term median PFS and OS of patients carrying the ERCC1 118 C/C allele were significantly longer than those of patients carrying a C/T or T/T allele (P < 0.01). Besides, positive correlation was observed between the differentiation status and tumor staging as well as the C/C genotype.

Conclusions: Our results suggest that this polymorphism of ERCC1 at codon 118 is associated with patient response to cisplatin-based chemotherapy in treatments of late-stage NSCLC. Moreover, by assaying this SNP in blood cells, the ERCC1 codon 118 may represent a valuable biomarker in developing individualized treatments for NSCLC patients.

Fig. 1

Kalpan–Meier curves for PFS (a) and OS (b) of late-stage NSCLC patients with a C/C genotype (green line), or otherwise (C/T + T/T, blue line) that received platinum-based chemotherapy