title: Glutathione S-transferase P1 and DNA polymorphisms influence response to chemotherapy and prognosis of bone tumors.
abstract: Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the influence of GSTP1, ERCC1 and ERCC2 polymorphisms on response to chemotherapy among osteosarcoma patients, and the significnace of these genes for prognosis. A total of 187 patients with osteosarcoma were administered methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine. GSTP1, ERCC1 and ERCC2 polymorphisms were genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. Some 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.3). Individuals with the ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated that GSTP1 and ERCC2 Lys751Gln polymorphisms might be candidate pharmacogenomic factors to be explored in the future to identify osteosarcoma patients who might benefit from chemotherapy.
authors: Department of Orthopaedics, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, China.
authors: Li-Min
authors: LM
authors: Yang
authors: Xiu-Hua
authors: XH
authors: Li
authors: Cui-Fen
authors: CF
authors: Bao
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin; D008727:Methotrexate