Background: RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis and the response to gemcitabine. Two single nucleotide polymorphisms (SNP) in the RRM1 gene (RR37 and RR524) impact promoter activity and are associated with prognosis. The excision repair cross-complementation group 1 protein (ERCC1) is associated with platinum resistance. A SNP of the ERCC1 gene (T19007C) has been reported as a prognostic marker in platinum-treated non-small-cell lung cancer (NSCLC).
Materials and methods: Patients with stage IIIB or IV NSCLC were treated with gemcitabine and platinum (GP) as first-line chemotherapy. Adenocarcinoma was the most frequent histological type, followed by squamous cell carcinoma and then other types. SNP were analyzed with real time-polymerase chain reaction using genomic DNA extracted from peripheral blood.
Results: Based on responses to GP patients were classified as responders or non-responders. The response rate was significantly higher in patients with the RR AC-CT genotype (35/64, 54.7%) compared to those with the RR CC-TT genotype (56/147, 38.1%, P= 0.025). No significant difference in response rate was observed according to ERCC1 genotype. In 128 patients with non-squamous cell lung cancer, RR AC-CT + ERCC1 CC (63.2%) and RR AC-CT + ERCC1 CT/TT (61.9%) showed higher response rates compared to RR CC-TT + ERCC1 CC (36.5%), and RR CC-TT + ERCC1 CT/TT (22.2%; P= 0.004). Progression-free and overall survival times were not different between genotypes.
Conclusions: We observed significantly different responses to the GP regimen according to SNP of the RRM1 and ERCC1 genes.
Keywords: ERCC1; RRM1; gemcitabine; non-small-cell lung carcinoma; platinum.
© 2011 Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.