期刊
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 107, 期 7, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djv101
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- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD [U10 CA180886-01, U24 CA114766]
- WWWW (QuadW) Foundation, Inc.
- Ontario Cancer Research Network
- Canadian Institutes of Health Research
- Ontario Research Fund
- Canadian Foundation for Innovation
The etiologic contribution of germline genetic variation to sporadic osteosarcoma is not well understood. Osteosarcoma is a sentinel cancer of Li-Fraumeni syndrome (LFS), in which approximately 70% of families meeting the classic criteria have germline TP53 mutations. We sequenced TP53 exons in 765 osteosarcoma cases. Data were analyzed with chi(2) tests, logistic regression, and Cox proportional hazards regression models. We observed a high frequency of young osteosarcoma cases (age <30 years) carrying a known LFS- or likely LFS-associated mutation (3.8%) or rare exonic variant (5.7%) with an overall frequency of 9.5%, compared with none in case patients age 30 years and older (P < .001). This high TP53 mutation prevalence in young osteosarcoma cases is statistically significantly greater than the previously reported prevalence of 3% (P = .0024). We identified a novel association between a TP53 rare variant and metastasis at diagnosis of osteosarcoma (rs1800372, odds ratio = 4.27, 95% confidence interval = 1.2 to 15.5, P = .026). Genetic susceptibility to young onset osteosarcoma is distinct from older adult onset osteosarcoma, with a high frequency of LFS-associated and rare exonic TP53 variants.
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