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Onco Targets Ther. 2016 Feb 19;9:807-13. doi: 10.2147/OTT.S99106. eCollection 2016.

Association of polymorphisms in WWOX gene with risk and outcome of osteosarcoma in a sample of the young Chinese population.

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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.
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People's Republic of China.


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.


SNP; WWOX; metastasis; osteosarcoma; susceptibility

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