Wu Ying-Guang, Li Hong-Fu, Ren Yan-Jun, Zou De-Bo, Zhang Kai-Ning, Xiao Xing
Department of Spine Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong, China,
Department of Orthopedics, Second Hospital of Haibei Tibetan Autonomous Region, Menyuan, Qinghai, China.
Cancer Manag Res. 2018 Oct 25;10:4959-4967. doi: 10.2147/CMAR.S177452. eCollection 2018.
The association of single-nucleotide polymorphisms at X-ray repair cross-complementing group-1 (XRCC1) with osteosarcoma (OS) development has not been fully clear to date. The aim of the present study is to evaluate the association of XRCC1 polymorphisms with risk, clinicopathologic features, and prognosis in Chinese OS patients.
A total of 146 patients with primary OS and 248 age- and gender-matched controls were included in the present study. The frequencies of four XRCC1 polymorphisms (rs25487, rs1799782, rs25489, and rs3213245) were determined between OS patients and controls. The association of XRCC1 polymorphism with clinicopathologic characteristics, prognosis, and XRCC1 expression was further evaluated.
Compared with TT genotype, individuals carrying the minor C allele (TC+ CC) of rs3213245 had significantly increased risk of OS development (OR =1.83, 95% CI 1.14-3.00). OS patients carrying TC genotype and C allele at rs3213245 were more likely to be with larger tumor size and metastasis. Survival analysis demonstrated that OS patients carrying C allele (TC + CC) at rs3213245 had shorter survival time than those with TT genotype. The T to C substitution at rs3213245 could decrease gene transcriptional activity in vitro. XRCC1 mRNA and protein expression levels were lower in OS patients carrying TC or CC genotype at rs3213245. Besides, no significant association of rs25487, rs1799782, and rs25489 with OS was observed.
In conclusion, these findings revealed that XRCC1 rs3213245 polymorphism was associated with increased risk of OS, which could affect XRCC1 expression in vitro and in vivo.
X射线修复交叉互补基因1（XRCC1）单核苷酸多态性与骨肉瘤（OS）发生之间的关联迄今尚未完全明确。本研究旨在评估XRCC1多态性与中国骨肉瘤患者的发病风险、临床病理特征及预后的相关性。
本研究共纳入146例原发性骨肉瘤患者和248例年龄及性别匹配的对照。测定骨肉瘤患者与对照之间4种XRCC1多态性（rs25487、rs1799782、rs25489和rs3213245）的频率。进一步评估XRCC1多态性与临床病理特征、预后及XRCC1表达的相关性。
与TT基因型相比，携带rs3213245次要C等位基因（TC + CC）的个体发生骨肉瘤的风险显著增加（OR = 1.83，95%CI 1.14 - 3.00）。携带rs3213245的TC基因型和C等位基因的骨肉瘤患者更易出现肿瘤体积较大及发生转移。生存分析表明，携带rs3213245的C等位基因（TC + CC）的骨肉瘤患者的生存时间短于TT基因型患者。rs3213245处的T到C替换可降低体外基因转录活性。携带rs3213245的TC或CC基因型的骨肉瘤患者的XRCC1 mRNA和蛋白表达水平较低。此外，未观察到rs25487、rs1799782和rs25489与骨肉瘤有显著关联。
总之，这些研究结果表明，XRCC1 rs3213245多态性与骨肉瘤发病风险增加相关，这可能在体外和体内影响XRCC1表达。
