Effect of hENT1 polymorphism G-706C on clinical outcomes of gemcitabine-containing chemotherapy for Chinese non-small-cell lung cancer patients

Aim: To identify the single-nucleotide polymorphism (SNP) of hENT1 G-706C that is associated with response to gemcitabine-containing chemotherapy, and to determine the prognosis in patients with non-small-cell lung cancer (NSCLC).

Methods: Patients with stage III (A+B) or IV NSCLC were recruited for this study (n=225). Each subject received gemcitabine-containing chemotherapy. The association between human equilibrative nucleoside transporter 1 (hENT1) polymorphism G-706C (rs61758845) and therapeutic effect was evaluated. The SNP hENT1 G-706C was genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays.

Results: The polymorphic genotype and the allele frequency of hENT1 G-706C was significantly different between chemotherapy responders and non-responders; to be specific, the response rate of patients carrying an hENT1-706 GG allele was higher than that of patients with a GC or CC genotype. Logistic regression analysis showed that having the GC or CC genotypes was associated with a higher risk of being a non-responder compared with having the GG genotype (OR=2.34, 95% CI: 1.14-4.80; P=0.02). The overall survival in patients with the GG genotype was significantly longer than in those with GC or CC genotype (19.0 versus 15.1 months, P<0.001). The hazard ratio for the (GC+CC) genotype was 1.89 (95% CI: 1.23-2.90) compared with GG carriers (P=0.004).

Conclusions: The hENT1 genetic polymorphism of hENT1 G-706C was associated with response to the gemcitabine-containing chemotherapy and prognosis of NSCLC. Moreover, assaying this SNP in blood cells may represent a valuable biomarker for individualized treatment for NSCLC patients.