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Endothelin‐1 gene polymorphisms and risk of chemoresistant pediatric osteosarcoma
Author(s) -
Zhou Yu,
Liu Bo,
Wang Min,
Ni Jiangdong
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24790
Subject(s) - medicine , haplotype , single nucleotide polymorphism , osteosarcoma , allele , oncology , case control study , disease , genotype , gene , pathology , genetics , biology
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. Procedure 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. Pediatr Blood Cancer 2014;61:612–617. © 2013 Wiley Periodicals, Inc.