title: Endothelin-1 gene polymorphisms and risk of chemoresistant pediatric osteosarcoma.
abstract: BACKGROUND
  Osteosarcoma (OS) is the most common childhood bone cancer. Chemoresistance is the principal reason for poor survival and disease recurrence in OS patients, and ET-1 reportedly plays an important role in the development of chemoresistance in OS cells. In the present study, we for the first time explored the association of endothelin-1 (ET-1) SNPs and haplotypes with the risk of chemoresistant pediatric OS.
  
  
  METHODS
  We genotyped three SNPs (rs1800541, rs2070699, and rs5370) in the ET-1 gene in a case-control study, using 350 pairs of age, sex, and tumor location and stage matched pediatric patients with OS. Patients who showed <90% tumor necrosis after neochemotherapy were defined as poor responders (cases), and those who showed ≥90% tumor necrosis were defined as good responders (controls).
  
  
  RESULTS
  The G allele at rs1800541 and the G allele at rs2070699 were associated with reduced and increased risk of chemoresistant OS, respectively. The rs1800541-rs2070699 haplotypes TG and GT were respectively associated with increased (P = 0.012; adjusted OR, 1.82; 95% CI, 1.10-5.65) and reduced (P = 0.009; adjusted OR, 0.25; 95% CI, 0.14-0.84) risk of chemoresistant OS. The TG and the GT haplotypes have a gene-dosage effect on increasing and decreasing the ET-1 expression in primary OS tumor cells from chemoresistant pediatric OS subjects, respectively.
  
  
  CONCLUSIONS
  This study provides the first evidence of an association between the ET-1 gene SNPs and haplotypes and the risk of chemoresistant pediatric OS, potentially adding new insights into the pathophysiology and treatment of chemoresistant OS.
authors.affiliation: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jiangdong
authors.initials: J
authors.lastname: Ni
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis
chemical_list: D019332:Endothelin-1
keywords: chemoresistance; endothelin-1; haplotype; osteosarcoma; single nucleotide polymorphism