PRINCIPLES: Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of GSTP1 and XRCC1 involved in glutathione metabolic and DNA repair pathways may explain inter individual differences in chemosensitivity and clinical outcome in NSCLC patients treated with platinum-based regimens. METHODS: We used DNA sequencing methods to evaluate genetic polymorphisms of the GSTP1A313G and XRCC1G28152A in 111 patients with stage IV NSCLC treated with platinum-based chemotherapy. Clinical response was evaluated according to RECIST criteria after 2-3 cycles of chemotherapy and time to progression (TTP) was calculated from the time of initial treatment to disease progression. RESULTS: GSTP1A313G and XRCC1G28152A polymorphisms, both alone and in combination, were significantly associated with response to treatment and clinical outcome (p <0.05) in NSCLC patients treated with platinum-based chemotherapy. These polymorphisms independently predicted clinical outcome even after taking into account age, gender, tumour histology, tumour differentiation and chemotherapy regimens. CONCLUSION: Genetic polymorphisms of GSTP1 and XRCC1 may be important predictive factors in platinum-treated patients with advanced NSCLC. Assessment of genetic variations of GSTP1 and XRCC1 could facilitate therapeutic decisions for individualised therapy in advanced NSCLC.
PRINCIPLES: Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of GSTP1 and XRCC1 involved in glutathione metabolic and DNA repair pathways may explain inter individual differences in chemosensitivity and clinical outcome in NSCLCpatients treated with platinum-based regimens. METHODS: We used DNA sequencing methods to evaluate genetic polymorphisms of the GSTP1A313G and XRCC1G28152A in 111 patients with stage IV NSCLC treated with platinum-based chemotherapy. Clinical response was evaluated according to RECIST criteria after 2-3 cycles of chemotherapy and time to progression (TTP) was calculated from the time of initial treatment to disease progression. RESULTS: GSTP1A313G and XRCC1G28152A polymorphisms, both alone and in combination, were significantly associated with response to treatment and clinical outcome (p <0.05) in NSCLCpatients treated with platinum-based chemotherapy. These polymorphisms independently predicted clinical outcome even after taking into account age, gender, tumour histology, tumour differentiation and chemotherapy regimens. CONCLUSION: Genetic polymorphisms of GSTP1 and XRCC1 may be important predictive factors in platinum-treated patients with advanced NSCLC. Assessment of genetic variations of GSTP1 and XRCC1 could facilitate therapeutic decisions for individualised therapy in advanced NSCLC.
Authors: Most Umme Bushra; Sanzana Fareen Rivu; Ali Ehsan Sifat; Noor Ahmed Nahid; Maizbha Uddin Ahmed; Mir Md Abdullah Al-Mamun; Mohd Nazmul Hasan Apu; Md Siddiqul Islam; Md Reazul Islam; Mohammad Safiqul Islam; Abul Hasnat Journal: Mol Biol Rep Date: 2020-09-03 Impact factor: 2.316