Study On The Relationship Between Efficacy And Toxicity Of Cisplatin And Single Nucleotide Polymorphisms In Advanced Non-small Cell Lung Cancer Patients

Objective：To investigate the assosiation of gene polymorphisms of GSTP1A313G、ATP7A C767G、XRCC1A399G and ERCC1C118T with the efficacy and toxicity ofcisplatin-based chemotherapy in advanced non-small cell lung cancer.Method:97advanced NSCLC patients who were treated with cisplatin-basedchemotherapy participated in this study. Polymerase Chain Reaction and RestrictionFragment Length Polymorphism (PCR-RFLP) and Pyrosequencing were used to typethe SNP of GSTP1A313G、ATP7A C767G、XRCC1A399G and ERCC1C118T. Theshort-term efficacy were evaluated by Response Rate (RR) and Disease Control Rate(DCR). The long-term efficacy were evaluated by Progression-Free Survival (PFS).The grade of toxicity were evaluated by Common Terminology Criteria for AdverseEvents.Results:1、The GSTP1A313G mutant allele G carriers suffered lymphocyte toxicity is0.086times the GSTP1313AA-carriers in advanced NSCLC patients treated withcisplatin-based chemotherapy (95%CI,0.010-0.758, P=0.027). No significantassociations were noted between GSTP1A313G polymorphisms and efficiency(P>0.05).2、There is no significant difference between the efficiency and toxicity of cisplatinand SNP of ATP7A C767G (P>0.05).3、Patient with a homozygous CC genotype of ERCC1C118T (PFS=221.0days) hadan increased PFS compared with that of patient with one or two T allels (PFS=148.9days)(P=0.027). No significant associations were noted between ERCC1 C118T polymorphisms and short-term efficacy (P>0.05).4、XRCC1A399G mutant allele A appear associated with notable higher risk ofhematological toxicity (OR=2.549,95%CI,1.064-6.104, P=0.036) andlymphocyte toxicity (OR=2.672,95%CI,1.012-7.051, P=0.047) in advancedNSCLC patients treated with cisplatin-based chemotherapy. There is nosignificant difference between the efficiency of cisplatin and SNP of XRCC1A399G (P>0.05).Conclusion：The gene polymorphism of ERCC1C118T is an effective predictor inadvanced NSCLC patients treated cisplatin-based chemotherapy. The GSTP1A313Gwild-type gene AA and XRCC1A399G mutant allele A may increase the risk oflymphocyte toxicity in advanced NSCLC patients treated with cisplatin-basedchemotherapy. Advanced NSCLC patients with XRCC1399A variant would suffermore hematological toxicity when treated by cisplatin-based chemotherapy.