PDF(Pubmed)
Abstract：
UNASSIGNED: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children.
UNASSIGNED: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3.
UNASSIGNED: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA.
UNASSIGNED: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.
UNASSIGNED: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3.
UNASSIGNED: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA.
UNASSIGNED: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.
摘要：
■横纹肌肉瘤（RMS）是儿童中最常见的软组织肉瘤，某些基因中的单核苷酸多态性（SNP）会影响RMS的风险。尽管FOXO3已被报道在包括RMS在内的多种癌症中，FOXO3多态性在RMS中的作用尚不清楚.在这项病例对照研究中，我们评估了FOXO3SNP与儿童RMS风险和预后的相关性.
■四个FOXO3SNP（rs17069665A>G，rs4946936T>C,rs4945816C>T和rs9400241C>A）在110例RMS病例和359例对照中进行基因分型。FOXO3多态性与RMS风险之间的关联通过比值比（ORs）和95％置信区间（CI）确定。使用Kaplan-Meier方法和对数秩检验估计rs17069665和rs4946936与RMS儿童总体生存率的关联。进行了硅片中的功能分析以估计rs17069665和rs4946936可能影响FOXO3调节的概率。
■我们发现rs17069665（GGvs.AA+AG,调整后的OR=2.96；95CI[1.10-3.32]；P=0.010）和rs4946936（TC+CCvs.TT,校正后的OR=0.48；95CI[0.25-0.90]；P=0.023）与RMS风险的增加和降低有关，分别。此外,rs17069665（P<0.001）和rs4946936（P<0.001）与RMS患者的总生存率降低和增加相关，分别。功能分析显示rs17069665和rs4946936可能通过改变与MYC的结合而影响FOXO3的转录和表达,CTCF,和/或RELA。
■本研究显示FOXO3多态性影响儿童RMS易感性和预后,并可能改变FOXO3的表达。FOXO3多态性被认为是RMS易感性和预后的生物标志物。
■四个FOXO3SNP（rs17069665A>G，rs4946936T>C,rs4945816C>T和rs9400241C>A）在110例RMS病例和359例对照中进行基因分型。FOXO3多态性与RMS风险之间的关联通过比值比（ORs）和95％置信区间（CI）确定。使用Kaplan-Meier方法和对数秩检验估计rs17069665和rs4946936与RMS儿童总体生存率的关联。进行了硅片中的功能分析以估计rs17069665和rs4946936可能影响FOXO3调节的概率。
■我们发现rs17069665（GGvs.AA+AG,调整后的OR=2.96；95CI[1.10-3.32]；P=0.010）和rs4946936（TC+CCvs.TT,校正后的OR=0.48；95CI[0.25-0.90]；P=0.023）与RMS风险的增加和降低有关，分别。此外,rs17069665（P<0.001）和rs4946936（P<0.001）与RMS患者的总生存率降低和增加相关，分别。功能分析显示rs17069665和rs4946936可能通过改变与MYC的结合而影响FOXO3的转录和表达,CTCF,和/或RELA。
■本研究显示FOXO3多态性影响儿童RMS易感性和预后,并可能改变FOXO3的表达。FOXO3多态性被认为是RMS易感性和预后的生物标志物。
