Clinical outcome of cisplatin-based chemotherapy is associated with the polymorphisms of GSTP1 and XRCC1 in advanced non-small cell lung cancer patients.

ABSTRACT

INTRODUCTION: This study is to evaluate the association of polymorphisms of glutathione S-transferase P1 (GSTP1), copper-transporting P-type adenosine triphosphatase A (ATP7A) and X-ray repair cross-complementing group 1 (XRCC1) with the efficacy and toxicity of cisplatin-based treatment in advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: The outcomes of 97 advanced non-small cell lung cancer patients treated with cisplatin-based chemotherapy were estimated. GSTP1, ATP7A, and XRCC1 genetic polymorphisms were determined via polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Association of the polymorphisms with the efficacy and toxicity of cisplatin was analyzed, respectively. RESULTS: Significant associations were observed between GSTP1 A313G and response rate (RR) (p = 0.027), disease control rate (DCR) (p = 0.019), and progression-free survival (PFS) (p = 0.044), respectively. Patients with AG and GG of GSTP1 have notably lower risk of anemia (p = 0.046). XRCC1 A1196G was associated with the incidence of lymphopenia (p = 0.024) and diarrhea (p = 0.020). ATP7A C2299G was not related with RR, DCR, PFS, and the risk of toxicity. CONCLUSIONS: Advanced NSCLC patients with AA genotype of GSTP1 would obtain better curative effect followed with more risk of anemia when treated by cisplatin-based chemotherapy. ATP7A C2299G does not impact the efficacy and toxicity of cisplatin-based chemotherapy. XRCC1 1196A allele could predict the incidence of lymphopenia and diarrhea.