title: Single nucleotide polymorphisms in the NER pathway and clinical outcome of patients with bone malignant tumors.
abstract: The effects of polymorphisms in ERCC5, ERCC6, XPC, CCNH and MMS19L on osteosarcoma response to chemotherapy and the survival of the affected patients were assessed. Genotyping of ERCC5, ERCC6, XPC, CCNH and MMS19L was performed by PCR-RFLP assay. The median PFS was 12.8 months, and the median OS was 18.6 months. Individuals carrying homozygous genotypes of ERCC5 rs17655 and ERCC5 rs1047768 were more like to have good response to treatment, while those carrying homozygous genotypes of MMS19L rs29001322 showed poor response. Osteosarcoma patients carrying TT genotype of ERCC5 rs1047768 showed a significantly longer PFS (16.8 months) and OS (21.4 months) than CC genotype, with HRs(95% CI) of 0.31 (0.10-0.93) and 0.32 (0.06-0.97), respectively. Conversely, those with the TT genotype of MMS19L rs29001322 demonstrated shorter PFS and OS, the HRs (95% CI) being 2.23 (1.08-4.15) and 4.62 (1.45-16.08), respectively. Our findings showed polymorphisms in ERCC5 rs1047768 and MMS19L rs29001322 to be associated with clinical outcome of osteosarcoma patients undergoing chemotherapy.
authors.affiliation: Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University, Weihui, China. sunxiaohui_xxmu@163.com
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Sun
authors.forename: Wen-Gen
authors.initials: WG
authors.lastname: Hou
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhao
authors.forename: Yi-Lei
authors.initials: YL
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D056748:Cyclin H / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin; D056748:Cyclin H; D004265:DNA Helicases; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004720:Endonucleases; D008727:Methotrexate; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C534751:CCNH protein, human; C416322:MMS19 protein, human; C086984:XPC protein, human; C078673:ERCC6 protein, human