Zhang Niannian, Jiang Zhenghui, Ren Weifeng, Yuan Li, Zhu Yangyi
Department of Orthopedics, Shaoxing Shangyu People's Hospital, Shaoxing, People's Republic of China.
Division of Musculoskeletal Oncology, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China; Department of Orthopedics, The First People's Hospital of Wenling, Wenling, People's Republic of China.
Onco Targets Ther. 2016 Feb 19;9:807-13. doi: 10.2147/OTT.S99106. eCollection 2016.
The WW domain-containing oxidoreductase (WWOX) gene is a tumor suppressor gene, the abnormal expression of which will lead to osteosarcoma tumorigenesis. Polymorphisms of the WWOX gene are associated with the risk of several malignancies. We hypothesized that genetic variations in the WWOX gene were related to osteosarcoma risk and outcome. In this case-control study, we recruited 276 young osteosarcoma patients and 286 controls from the East Chinese population and genotyped seven tag single-nucleotide polymorphisms (SNPs) of the WWOX gene (rs10220974C>T, rs12918952G>A, rs3764340C>G, rs1074963C>G, rs383362G>T, rs1424110A>G, and rs12828A>G). We discovered that two SNPs (rs3764340C>G and rs383362G>T) were associated with osteosarcoma risk. The CG genotype and dominant model of rs3764340 indicated elevated risk of osteosarcoma, and similar results were found for rs383362. Furthermore, rs3754340C>G was also related to grade and metastasis risk of osteosarcoma. Taken together, our results provide the first evidence that WWOX gene polymorphisms have the potential to be predictive factors for assessing risk and outcome of osteosarcoma.
含WW结构域的氧化还原酶（WWOX）基因是一种肿瘤抑制基因，其异常表达会导致骨肉瘤的发生。WWOX基因的多态性与多种恶性肿瘤的风险相关。我们推测WWOX基因的遗传变异与骨肉瘤的风险及预后有关。在这项病例对照研究中，我们从中国东部人群中招募了276名年轻骨肉瘤患者和286名对照，并对WWOX基因的7个标签单核苷酸多态性（SNP）（rs10220974C>T、rs12918952G>A、rs3764340C>G、rs1074963C>G、rs383362G>T、rs1424110A>G和rs12828A>G）进行了基因分型。我们发现两个SNP（rs3764340C>G和rs383362G>T）与骨肉瘤风险相关。rs3764340的CG基因型和显性模型表明骨肉瘤风险升高，rs383362也有类似结果。此外，rs3754340C>G还与骨肉瘤的分级和转移风险有关。综上所述，我们的结果首次证明WWOX基因多态性有可能成为评估骨肉瘤风险和预后的预测因素。
