Department of Orthopaedic Trauma, HongHui Hospital, Xi'an Jiaotong University, 555 Youyi East Road, Beilin District, Xi'an, 710053, Shaanxi, China.
Department of Neonatology, Xi'an Children's Hospital, Xi'an, Shaanxi, China.
Sci Rep. 2020 Sep 29;10(1):15939. doi: 10.1038/s41598-020-72995-4.
Accumulating evidence has shown that both MDM2 and GNRH2 might be related to Osteosarcoma (OS) susceptibility. The study aimed to evaluate the effects of common variants in MDM2 and GNRH2 genes on the risk and survival of osteosarcoma in Han populations from Northwest China. In the study, we recruited 2292 subjects including 596 OS patients and 1696 healthy controls and genotyped 16 selected tag SNPs (6 from GNRH2 and 10 from MDM2). Genetic association analyses were performed at the genotypic and allelic levels. Survival curves were made for OS patients with different genotypes. Two SNPs, rs1690916 (MDM2, P = 0.0002) and rs3761243 (GNRH2, P = 0.0004), were identified to be significantly associated with OS risk. Moreover, SNP rs3761243 was strongly associated with pathological fracture (P = 2.61 × 10), metastasis (P < 2.2 × 10), and Enneking stage (P < 2.2 × 10) in the OS group. Furthermore, survival curves based on different genotypes of SNP rs3761243 were found to be significantly different (P = 0.0003), suggesting increased risk with more copies of C alleles. Our results provide supportive evidence for genetic associations of MDM2 and GNRH2 genes with susceptibility to OS, and for the positive correlation of SNP rs3761243 in GNRH2 with the survival status of OS patients in Han populations from Northwest China.
越来越多的证据表明，MDM2 和 GNRH2 可能与骨肉瘤（OS）易感性有关。本研究旨在评估 MDM2 和 GNRH2 基因常见变异对中国西北地区汉族人群骨肉瘤发病风险和生存的影响。在这项研究中，我们招募了 2292 名受试者，包括 596 名骨肉瘤患者和 1696 名健康对照者，并对 16 个选定的标签 SNP（6 个来自 GNRH2，10 个来自 MDM2）进行了基因分型。在基因型和等位基因水平上进行了遗传关联分析。为不同基因型的 OS 患者绘制了生存曲线。两个 SNP，rs1690916（MDM2，P = 0.0002）和 rs3761243（GNRH2，P = 0.0004），被确定与 OS 风险显著相关。此外，SNP rs3761243 与骨肉瘤组的病理性骨折（P = 2.61 × 10）、转移（P < 2.2 × 10）和 Enneking 分期（P < 2.2 × 10）显著相关。此外，基于 SNP rs3761243 不同基因型的生存曲线存在显著差异（P = 0.0003），提示 C 等位基因拷贝数增加会增加风险。我们的结果为 MDM2 和 GNRH2 基因与 OS 易感性的遗传关联以及 GNRH2 中 SNP rs3761243 与中国西北地区汉族人群骨肉瘤患者生存状况的正相关提供了支持性证据。
