Single nucleotide polymorphisms in the NER pathway and clinical outcome of patients with bone malignant tumors

Asian Pac J Cancer Prev. 2013;14(3):2049-52. doi: 10.7314/apjcp.2013.14.3.2049.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / mortality
  • Child
  • Cisplatin / administration & dosage
  • Cyclin H / genetics
  • DNA Helicases / genetics
  • DNA Repair / genetics*
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / genetics
  • Endonucleases / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Neoplasm Metastasis
  • Nuclear Proteins / genetics
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics*
  • Osteosarcoma / mortality
  • Poly-ADP-Ribose Binding Proteins
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Survival Rate
  • Transcription Factors / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CCNH protein, human
  • Cyclin H
  • DNA excision repair protein ERCC-5
  • DNA-Binding Proteins
  • MMS19 protein, human
  • Nuclear Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • XPC protein, human
  • Endonucleases
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes
  • Cisplatin
  • Methotrexate