Meta Analysis Of RRM1,UGT1A1,ABCB1 Gene Polymorphisms And Efficacy And Safety Of Platinum Based Combination Chemotherapy For Non-small Cell Lung Cancer

Objective:Systematic review of ribonucleotide reductase 1 subunit(RRM 1)(-37C>A)/(-524 T>C),multidrug resistance transporter ATP binding cassette transmembrane transporter superfamily B subgroup 1(ABCB1)(2677 G>T/A)/(3435C>T),drug metabolizing enzyme uridine diphosphate glucuronyltransferase 1A(UGT1A1)*28(TA6>TA7)genetic polymorphism and correlation between efficacy and safety of platinum combined with the third generation chemotherapeutic drugs gemcitabine,paclitaxel and irinotecan in patients with NSCLC.Method:Computer search database: China knowledge Network(CNKI),VIP(VIP),Wanfang(WANGFANG),China Biomedical Literature Database(CBM),Pub Med,Embase,Cochrane Library and FMJS(Matt Silvor),searching the literatures about the efficacy and safety of platinum combined with the third generation chemotherapeutic drug GEM/PTX/CPT-11 in the treatment of NSCLC patients published from the establishment of the database to January 2021.The qualified literature was screened by PICO principle.The quality of the included literature was evaluated by Newcastle-Ottawa Scale literature quality evaluation table,and the literature data were extracted.The objective remission rate(ORR)and grade 3 toxicity were used in the outcome index.Rev Man5.3 software was used for Meta analysis.Results:A total of 16 articles including 8 articles of GEM combined with platinum,6articles of CPT-11 alone or combined platinum were analyzed by quantitative Meta,and 2 articles of PTX combined with platinum were analyzed by qualitative Meta to evaluate the correlation between gene polymorphism and the efficacy and safety of NSCLC platinum combination drugs.The RRM1 C37 A gene dominant model(AA+CA)vs.CC included 655 patients,the allele model C vs.A total gene frequency was 1310,the recessive model(CC+CA)vs.AA included 665 patients,the UGT1A1*28 gene dominant model(TA6TA7+TA7TA7)vs TA6TA6 included 332 patients,the allele model TA6 vs TA7 total gene frequency was 392,and the recessive model(TA6TA6+TA6TA7)vs TA7TA7 included 230 patients.RRM1 C37 A locus had no significant effect on the efficacy of GEM combined with platinum chemotherapy.The subgroup analysis of RRM1 C37 A showed that there was a significant effect of RRM1 C37 A genotype on the efficacy of GEM combined with platinum chemotherapy in Caucasians [(AA+CA)vs.CC;OR=0.41,95%CI:0.20-0.85,P=0.02)].RRM1 T524 C had no significant effect on the efficacy of GEM combined with platinum chemotherapy.The number of neutropenia events of grade 3-4 neutropenia with TA7TA7 genotype at UGT1A1*28 polymorphism sites was higher than other genotype[(TA6TA6+TA6TA7)vs TA7TA7;OR=0.19,95%CI:0.09-26.22,P=0.02)].The polymorphism of ABCB1 C3435 T and G2677T/A loci is controversial with the combination of PTX and platinum in the treatment of NSCLC.Conclusion:Meta-analysis results showed that RRM1 C37 A and T524 C polymorphism sites are not predictors of the efficacy of GEM combined with platinum in the treatment of NSCLC patients with stage III and above.The ethnic factor in the subgroup analysis is the source of heterogeneity of the RRM1 C37 A gene polymorphism.ABCB1 C3435 T and G2677T/A polymorphisms are inconsistent with the results of PTX combined with platinum.It still needs to be confirmed by larger and more rigorous prospective studies.UGT1A1*28 is closely related to the level 3 or higher neutrophil adverse reaction of CPT-11,which may be a predictor of its toxicity.