Kan Yutian, Ge Peng, Wang Xinyuan, Xiao Gangfeng, Zhao Haifeng
1Department of Hematology and Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin, 300060 People's Republic of China.
2Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin, People's Republic of China.
Cancer Cell Int. 2018 Oct 22;18:163. doi: 10.1186/s12935-018-0659-z. eCollection 2018.
The aim of the study was to explore the association between the SIRT1 single nucleotide polymorphism (SNP) rs3758391 and diffuse large B cell lymphoma (DLBCL) in a Chinese Han population.
206 patients diagnosed with DLBCL and 219 healthy individuals were recruited in the present study. The genotyping of SIRT1 rs3758391 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. The SIRT1 mRNA expression was detected by the Taqman real-time quantitative PCR.
Our study showed that the genotype TT and allele T frequency were significantly higher in DLBCL patients than that of controls (p = 0.02 and 0.01, respectively). No statistical differences were observed between SIRT1 rs3758391 and clinical characteristics of DLBCL patients. Analysis of the polymorphism revealed an increased risk of DLBCL associated with TC and TT genotype when compared with CC genotype [odds ratio = 2.621 and 3.518, respectively; 95% confidence interval (CI) 1.249-5.501 and 1.675-7.390, respectively; p = 0.011 and 0.001, respectively]. The survival analysis indicated that the patients with C allele had higher overall survival rate than those with genotype TT (p = 0.005). Furthermore, multivariate Cox regression analysis showed that the TT genotype of SIRT1 SNP rs3758391 was an independent poor prognostic factor for DLBCL patients (p = 0.006, HR 1.981, 95% CI 1.215-3.231). The SIRT1 mRNA expression was significantly upregulated in DLBCL patients than that of controls (p < 0.001). In addition, the SIRT1 mRNA expression of TT subgroup was upregulated compared with TC/CC subgroup in DLBCL patients (p < 0.001).
These results suggest that the SIRT1 rs3758391 polymorphism is associated with the risk and survival rate of DLBCL in Chinese Han population.
本研究旨在探讨中国汉族人群中SIRT1单核苷酸多态性(SNP)rs3758391与弥漫性大B细胞淋巴瘤(DLBCL)之间的关联。
本研究招募了206例经诊断患有DLBCL的患者和219名健康个体。采用聚合酶链反应-限制性片段长度多态性方法检测SIRT1 rs3758391多态性的基因分型。通过Taqman实时定量PCR检测SIRT1 mRNA表达。
我们的研究表明,DLBCL患者中基因型TT和等位基因T的频率显著高于对照组(p分别为0.02和0.01)。在SIRT1 rs3758391与DLBCL患者的临床特征之间未观察到统计学差异。多态性分析显示,与CC基因型相比,TC和TT基因型与DLBCL风险增加相关[比值比分别为2.621和3.518;95%置信区间(CI)分别为1.249 - 5.501和1.675 - 7.390;p分别为0.011和0.001]。生存分析表明,携带C等位基因的患者总生存率高于基因型为TT的患者(p = 0.005)。此外,多因素Cox回归分析显示,SIRT1 SNP rs3758391的TT基因型是DLBCL患者独立的不良预后因素(p = 0.006,风险比1.981,95% CI 1.215 - 3.231)。DLBCL患者中SIRT1 mRNA表达显著高于对照组(p < 0.001)。此外,DLBCL患者中TT亚组的SIRT1 mRNA表达高于TC/CC亚组(p < 0.001)。
这些结果表明,SIRT1 rs3758391多态性与中国汉族人群中DLBCL的风险和生存率相关。