Meta-analysis Of The Association Between ABCB1 Gene Polymorphisms And Paclitaxel In The Treatment Of Breast Cancer

Background: The mutation rate of ABCB1 in breast cancer tissues is higher than that in normal tissues.The encoded P-glycoprotein of the ABCB1 gene is an important transmembrane transporter on the cell membrane and is an ATP-dependent efflux pump with extensive substrate specificity.P-gp is excreted in the intestine cavity,bile duct,urine,etc,by combining with various exogenous substances and other substrates(including drugs,such as paclitaxel,etc.),and is regulated in pharmacokinetics.The source drug-the concentration of P-gp substrate,thereby reducing the therapeutic effect of the drug.At the same time,the correlation between ABCB1 gene polymorphism and paclitaxel chemotherapy in other tumors has been increasingly reported as lung cancer,ovarian cancer and so on.We hope to verify the relationship between ABCB1 gene polymorphisms and chemotherapy regimens containing taxanes in the treatment of breast cancer.Methods: Systematic search PubMed,EMBase,Web of Science,Cochrane Library,China Knowledge Network,Wanfang Database,Weipu Chinese Sci-Tech Periodical database,collecting information about ABCB1 gene polymorphism and taxane-containing chemotherapy regimen for breast cancer.The research literature on the relationship between cancer chemotherapy efficacy and chemotherapy-induced hematologic toxicity,and the search time limit were built from each database to March 17,2018.The two reviewers independently selected and extracted the data according to the inclusion and exclusion criteria.Then they used the random effects model to evaluate the combined data.Meta-analysis was performed using RevMan 5.3 software and STATA 12.0 statistical software was used for sensitivity analysis and publication bias assessment.Results : A total of 5 studies and 592 breast cancer patients were included.Breast cancer patients with C3435 T CC genotype were less effective in chemotherapy with paclitaxel-based chemotherapy than breast cancer patients with C3435 T TC + TT genotype.Heterogeneity between the groups was statistically significant(OR:0.46,95%CI:0.22-0.98,I2=46%,P=0.04);breast cancer patients carrying the C3435 T C allele are less effective than paclitaxel-based chemotherapy regimens in breast cancer patients with the C3435 T T allele.The efficiency was low and the heterogeneity between groups was statistically significant(OR: 0.57,95% CI: 0.41-0.81,I2=0%,P=0.002).Breast cancer patients with C3435 T CC genotype had lower incidence of III-IV neutropenia with paclitaxel-based chemotherapy than breast cancer patients with C3435 T TC + TT genotype.The heterogeneity between groups was statistically significant.(OR: 0.12,95% CI: 0.04-0.40,I2=0%,P=0.0005);Breast cancer patients carrying the C3435 T C allele have chemotherapy regimens involving paclitaxel compared to breast cancer patients with the C3435 T T allele.The incidence of III-IV neutropenia was low,and the heterogeneity between the groups was statistically significant(OR: 0.43,95% CI: 0.29-0.63,I2=0%,P<0.0001).G2677T/A genotype and alleles between breast cancer,chemotherapy efficacy with paclitaxel chemotherapy and the incidence of III-IV neutropenia were not significantly different.Conclusion: Our study systematically reviewed existing studies on the relationship between genetic polymorphisms of ABCB1 C3435 T,ABCB1 G2677T/A,and taxane-containing chemotherapy regimens in the treatment of breast cancer chemotherapy and chemotherapy-induced hematologic toxicity.To verify the effect of genetic polymorphisms of ABCB1 C3435 T and ABCB1 G2677T/A on chemotherapy in patients with breast cancer.The results showed that the polymorphism of ABCB1 gene C3435 T was related to the chemotherapy effect and blood side effects of paclitaxel in breast cancer patients.