Effect of ABCB1 polymorphism on the clinical outcome of osteosarcoma patients after receiving chemotherapy

Abstract

Objective: To investigate the role of three genetic polymorphisms of ABC proteins in response to chemotherapy and overall survival of osteosarcoma patients. Methods: A prospective study was conducted. Genotyping analyses of ABCB1 C3435T, ABCG2 C421A, and ABCC3 C-211T were conducted using the TaqMan methodology. Multivariate Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% CI of effect of each genotype of ABCB1 C3435T, ABCG2 c421A, and ABCC3 C-211T on PFS and OS. Results: During the follow-up period, 135 patients (74.18%) were alive and 47 died (25.82). The median follow-up periods were 36.7 months. Individuals carrying with ABCB1 3435TT genotype and T allele showed less likely to have a poor response to chemotherapy. Cox regression analysis showed that individuals with ABCB1 TT genotype and T allele were associated with high risk of death from osteosarcoma when compared with wide-type genotype. However, we did not find significant association between ABCG2 C421A and ABCC3 C-211T polymorphisms and overall survival of osteosarcoma. Conclusion: ABCB1 C3435T polymorphism may be used as a genetic predictor of clinical outcome in osteosarcoma patients treated with chemotherapy. However, no association was found between polymorphisms in ABCG2 C421A and ABCC3 C-211T and clinical outcome of osteosarcoma.