EFFECTS OF ERCC1, GSTP1 AND CTR1 POLYMORPHISMS ON THE TREATMENT RESPONSES AND TOXICITIES OF PLATINUM-BASED CHEMOTHERAPY IN ADVANCED NON-SMALL CELL LUNG CANCER PATIENTS

Abstract

The genetic polymorphisms involved in platinums’ action appear to impact on clinical outcomes in patients treated with platinum-based regimens. Objectives of this study were to investigate the effects of ERCC1, GSTP1 and CTR1 polymorphisms on treatment response and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy. This prospective cohort study enrolled 74 advanced NSCLC participants received treatment at out-patient department of King Chulalongkorn Memorial Hospital, Bangkok. The polymorphisms of ERCC1 rs11615, GSTP1 rs1695 and CTR1 rs12686377 genes were 27.7%, 25% and 22.3%, respectively. There was no association between genetic polymorphisms and treatment response (P > 0.05). However, we found some genetic polymorphisms were related to some toxicity. Patients with GSTP1 polymorphism (AG and GG) had approximate 2.8-fold higher incidence of neutropenia than a AA genotype (95% CI, 1.033–7.614), similar to CTR1 polymorphism which was associated with weight loss, patients carrying homozygous wild type GG had higher incidence of weight loss (26.3% vs. 0%) compared to whom with genetic polymorphism (GT and TT). This study indicated that genetic polymorphisms should be considered in the selection of proper chemotherapy regimen in advanced NSCLC patients especially for prediction of adverse effects from the treatment.