Ji Wei-Ping, He Neng-Bin
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai, China.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):894-9. eCollection 2015.
The aim of the present study was to evaluate the influence of polymorphisms in NER and HRR pathways on the response to cisplatin-based treatment and clinical outcome in osteosarcoma patients. 214 osteosarcoma patients treated with cisplatin-based chemotherapy were collected between January 2008 and January 2011. Genotypes of ERCC1 rs11615, ERCC2 rs1799793 and rs13181, NBN rs709816, RAD51 rs1801320, and XRCC3 rs861539 were conducted by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) assay. By conditional logistic regression analysis, patients carrying CC genotype of ERCC1 rs11615 showed a significant more good responder than TT genotype, and the OR (95% CI) was 2.51 (1.02-6.85). In the Cox proportional hazards model, after adjusting for potential confounding factors, we found that individuals carrying CC genotype of ERCC1 rs11615 was associated with decreased risk of death from osteosarcoma, and the HR (95% CI) was 0.43 (0.15-0.93). In conclusion, our results suggest that ERCC1 rs11615 polymorphism in the DNA repair pathways play an important role in the response to chemotherapy and overall survival of osteosarcoma.
本研究的目的是评估核苷酸切除修复（NER）和同源重组修复（HRR）途径中的多态性对骨肉瘤患者顺铂治疗反应及临床结局的影响。2008年1月至2011年1月期间收集了214例接受顺铂化疗的骨肉瘤患者。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析检测了ERCC1 rs11615、ERCC2 rs1799793和rs13181、NBN rs709816、RAD51 rs1801320以及XRCC3 rs861539的基因型。通过条件逻辑回归分析，携带ERCC1 rs11615 CC基因型的患者比TT基因型患者显示出显著更多的良好反应者，比值比（OR，95%可信区间）为2.51（1.02 - 6.85）。在Cox比例风险模型中，在调整潜在混杂因素后，我们发现携带ERCC1 rs11615 CC基因型的个体与骨肉瘤死亡风险降低相关，风险比（HR，95%可信区间）为0.43（0.15 - 0.93）。总之，我们的结果表明DNA修复途径中的ERCC1 rs11615多态性在骨肉瘤化疗反应和总生存中起重要作用。
