Liu Shizhang, Yi Zhi, Ling Ming, Shi Jiyuan, Qiu Yusheng, Yang Shujuan
Department of Orthopaedic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Tumour Biol. 2014 Oct;35(10):9897-904. doi: 10.1007/s13277-014-1917-x. Epub 2014 Jul 5.
Genetic polymorphisms in drug metabolism and transport genes can influence the pharmacokinetics and pharmacodynamics of chemotherapy drugs. We investigated the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. The association between the eight polymorphisms with response to chemotherapy and clinical outcome of patients was carried out by unconditional logistic regression analysis and Cox proportional hazard models. Of 186 patients, 98 patients showed good response to chemotherapy, 64 died, and 97 showed progression at the end of the study. Patients carrying ABCB1 rs1128503 TT genotype and T allele were more likely to have a good response to chemotherapy. ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were associated with poor response to chemotherapy. In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying ABCB1 rs1128503 TT genotype and T allele were associated with lower risk of progression-free survival (PFS) and overall survival (OS). ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were correlated with high risk of PFS and OS. The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter OS. In conclusion, variants of ABCB1 rs128503, ABCC3 rs4148416, and GSTP1 rs1695 are associated with response to chemotherapy and PFS and OS of osteosarcoma patients; these gene polymorphisms could help in the design of individualized therapy.
药物代谢和转运基因中的遗传多态性会影响化疗药物的药代动力学和药效学。我们研究了参与代谢和转运途径的基因在骨肉瘤患者化疗反应及临床结局中的作用。通过无条件逻辑回归分析和Cox比例风险模型分析了这8种多态性与患者化疗反应及临床结局之间的关联。186例患者中，98例对化疗反应良好，64例死亡，97例在研究结束时病情进展。携带ABCB1 rs1128503 TT基因型和T等位基因的患者对化疗更可能有良好反应。ABCC3 rs4148416 TT基因型和T等位基因以及GSTP1 rs1695 GG基因型和G等位基因与化疗反应不佳相关。在Cox比例风险模型中，在调整潜在混杂因素后，携带ABCB1 rs1128503 TT基因型和T等位基因的患者无进展生存期（PFS）和总生存期（OS）风险较低。ABCC3 rs4148416 TT基因型和T等位基因以及GSTP1 rs1695 GG基因型和G等位基因与PFS和OS的高风险相关。ABCB1 TT和GSTP1 GG基因型与较短的OS显著相关。总之，ABCB1 rs128503、ABCC3 rs4148416和GSTP1 rs1695的变异与骨肉瘤患者的化疗反应、PFS和OS相关；这些基因多态性有助于个体化治疗方案的设计。
