Association of Glutathione S-Transferase P1 (GSTP1) Gene Polymorphism with the Response to Platinum Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Abstract

Abstract Background Lung cancer is one of the most commonly diagnosed cancers and despite therapeutic advances, mortality remains high. Platinum based chemotherapy remains the mainstay of adjuvant or first line chemotherapy in non small cell lung cancer (NSCLC) treatment, pathophysiological features along with genetic background significantly influence therapeutic efficacy of platinum-based chemotherapy. GSTP1 gene is a member of the cytosolic superfamily of glutathione-S-transferases, which is responsible for phase II detoxification enzymes that convert various reactive metabolites to more water-soluble and less harmful forms by conjugating them with glutathione. The genetic polymorphism GSTP1 rs1695 is associated with decreased substrate specific catalytic activity and the reduced enzyme activity which may reduces platinum detoxification, thus promoting better response rates to platinum-based chemotherapy. Aim of the Work In the present study was aimed to investigate the association of GSTP1 gene polymorphism with the response to platinum based chemotherapy in patients with NSCLC in order to prevent the non necessary exposure to the toxic effect of chemotherapy. Patients and Methods The study was a retrospective cross sectional study conducted on 50 NSCLC patients who were recruited from the Oncology clinic in Ain Shams University Hospitals, twenty of them were responders to platinum based chemotherapy and the other 30 were not responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the GSTP1 rs1695 (A/G) polymorphism by real-time PCR was done for both the responders and the non responders group. Results There was no statistically significant difference between the responders’ and non responders’ groups regarding the genotypic distribution (p > 0.05). However, the G allele was significantly higher in the responders’ group compared to the non responders’ group with p value < 0.05. Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies of the GSTP1 rs 1695 among the responders and the non responders group, but despite that it showed that the A allele was significantly higher in the non responders’ group compared to the responders’ group. However, the G allele was significantly higher in the responders’ group compared to the non responders’ group. Further studies with higher sample size are needed to clarify the association.