Correlation Analysis Of Abcc2, The Abcb1 And Abcg2 Gene Polymorphism And Lung Cancer, Platinum Chemotherapy

Part I Association of ABCC2, ABCB1, ABCG2 Polymorphisms with Platinum-based Chemotherapy Response and Survival in Non-Small Cell Lung Cancer PatientsChemotherapy as the primary means of lung cancer treatment, its efficacy is only 18-40%. The main factor affecting chemotherapy outcome is drug resistance, of which platinum resistance is the most common.ABCC2, ABCB1 and ABCG2 which belong to ATP-binding cassette (ABC) family, are the main genes in drug metabolism and transport pathway, and associate with multidrug resistance. We assume that genetic variations on ABCC2, ABCB1 and ABCG2 may affect individual response to chemotherapy and survival of lung cancer patients. In order to test this hypothesis, we selected the 3 single nucleotide polymorphisms (SNP) in ABCC2,3 SNPs in ABCG2 and 1 SNP in ABCB1, and investigated the association of these SNPs with tumor response and overall survival in 445 patients with stage III and IV NSCLC treated with platinum-based chemotherapy. We determined the genotypes of these three polymorphisms by the MassArray method.We found that the common rs717620 homozygotes C/C was associated with a better treatment response (adjusted odds ratios [OR],1.84; 95%confidence interval [1],1.05-3.23), and the haplotype analysis also showed a trend for a better response. In stratified analysis, we found the same significant association in aged people, male, PS= 0-1, and Adenocarcinoma patients. No association was found between any SNP and overall survival.Our results suggest that, ABCC2 gene polymorphisms may play a role in platinum-based chemotherapy for lung cancer. Partâ…¡Association of ABCC2, ABCB1, ABCG2 Polymorphisms with Platinum-based Chemotherapy Severe Toxicity in Non-Small Cell Lung Cancer PatientsThe efficacy of lung cancer treatment is seriously restricted by chemotherapy side effects, which include hematologic toxicity and gastrointestinal toxicity. Hematologic toxicity contains anemia, agranulocytosis, leukocytopenia, and thrombocytopenia.ABCC2, ABCB1 and ABCG2 which belong to ATP-binding cassette (ABC) family, are the main genes in drug metabolism and transport pathway, and associate with multidrug resistance. We assume that genetic variations on ABCC2, ABCB1 and ABCG2 may affect individual chemotherapy toxicities of lung cancer patients. In order to test this hypothesis, we selected the 3 single nucleotide polymorphisms (SNP) in ABCC2,3 SNPs in ABCB1 and 1 SNP in ABCG2, and investigated the association of these SNPs with tumor response and overall survival in 445 patients with stageâ…¢and IV NSCLC treated with platinum-based chemotherapy. We determined the genotypes of these three polymorphisms by the MassArray method.We found by the first time that, patients with at least one rs3740066 variant (CT+TT) had increased risk of severe thrombocytopenia toxicity (adjusted OR,2.43; 95% CI,1.06-5.56; P= 0.034); and in subgroup analyses, this variant was associated with significantly increased risk of overall toxicity (adjusted OR,2.63; 95% CI, 1.17-5.95; P=0.02), hematologic toxicity (adjusted OR,3.80; 95%CI,1.62-8.87; P= 0.002), leukocytopenia, and thrombocytopenia. Moreover, we found the same associations between rs3740066 and thrombocytopenia in aged people, female, TNM stage IV, and Adenocarcinoma patients. In stratified analysis of chemotherapy regimens, we found variant genotype of rs2032582 in ABCB1 was significantly reduced the risk of Agranulocytosis (adjusted OR,0.36; 95% CI,0.13-0.94).A larger sample size and function analysis are needed for further investigation of the effect of ABCC2, ABCB1 and ABCG2 SNPs in platinum-based chemotherapy.