title: Predictive potential of ABCB1, ABCC3, and GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Shizhang
authors.initials: S
authors.lastname: Liu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yi
authors.forename: Ming
authors.initials: M
authors.lastname: Ling
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Shi
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Shujuan
authors.initials: S
authors.lastname: Yang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002648:Child; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D051549:Glutathione S-Transferase pi; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C114462:multidrug resistance-associated protein 3; C496556:GSTP1 protein, human