Prognostic significance of ABCB1 (MDR-1) gene variants (C1236T and G2677T) in lung cancer patients treated with platinum-based doublet chemotherapy

Abstract

ABCB1 gene encodes P-glycoprotein which is involved in the transport of substrates in and out of the cell. However, some of the substrates of P-glycoprotein include numerous structurally unrelated chemotherapeutic drugs which play a major role in drug resistance. Also, single nucleotide polymorphisms of ABCB1 gene are known to affect the structure and function of P-glycoprotein thus affecting their efflux system. The most common SNPs of ABCB1 gene that has been widely studied include rs1128503 (C1236T) and rs2032582 (G2677T). Various studies have evaluated the association of the above mentioned genetic polymorphisms of ABCB1 gene with overall survival of cancer (colorectal cancer, breast cancer, osteosarcoma, acute myeloid leukemia) on the basis of age, gender, smoking status, performance status and chemotherapy response. However, not much study has been done with regard to ABCB1 gene polymorphism and lung cancer. The aim of this study is to find the association between genetic polymorphisms rs1128503 and rs2032582, individually, with overall survival and treatment outcomes in lung cancer patients receiving platinum-based doublet chemotherapy in North Indian population. Methods: A total of 192 patients for C1236T and 153 patients for G2677T polymorphisms were evaluated. Genotyping was performed using PCR-RFLP method. Results: In the present work, we found no significant association of ABCB1 gene polymorphisms rs1128503 and rs2032582 with overall survival of lung cancer patients. However, statistically significant association of rs2032582 with SQCC was observed in patients harbouring heterozygous genotype GT (HR = 0.13, 95% CI = 0.00063 to 27.19, P = 0.01), mutant genotype TT (HR = 0.04, 95% CI = 0.0000071 to 301.98, P < 0.0001) and combined genotype (HR = 0.08, 95% CI = 0.000087 to 74.56, P = 0.001). Further, association of ABCB1 gene polymorphisms with chemotherapy response were examined. The results suggested no significant association of these polymorphisms with chemotherapy response.