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BACKGROUND The ras-association domain family 1 isoform A (RASSF1A) gene serves as a bona fide tumor suppressor gene. The polymorphisms in RASSF1A were previously reported to be associated with the risk of solid malignant tumors. We hypothesized herein that RASSF1A gene polymorphisms are involved in the risk and prognosis of osteosarcoma (OS). MATERIAL AND METHODS We recruited 279 young OS cases and 286 tumor-free controls from the east Chinese population. Five tagSNPs of RASSF1A gene (rs2236947A/C, rs2073497A/C, rs1989839C/T, rs72932987C/T, and rs4688728G/T) were genotyped. DNA was isolated from blood samples and then underwent PCR analysis for genotyping. RESULTS rs1989839C/T is an important predictor of osteosarcoma risk and outcome. The CT genotype of rs1989839 is highly related to elevated risk of osteosarcoma. Furthermore, rs1989839C/T is also associated with the Enneking stage of osteosarcoma and risk of lung metastasis. One of the other 4 SNPs, rs2236947A/C, shows a borderline significance in predicting osteosarcoma risk. CONCLUSIONS Our study is the first to prove that RASSF1A gene polymorphisms may potentially be predictive for osteosarcoma risk and prognosis.

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Ras-Association Domain Family 1 Isoform A (RASSF1A) Gene Polymorphism rs1989839 is Associated with Risk and Metastatic Potential of Osteosarcoma in Young Chinese Individuals: A Multi-Center, Case-Control Study