Department of Hematology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
PLoS One. 2012;7(12):e51640. doi: 10.1371/journal.pone.0051640. Epub 2012 Dec 10.
Dicer, an endonuclease in RNase III family, is essential for the RNA interference (RNAi) pathway. Aberrant expression of Dicer has been shown in various cancers including some subtypes of T cell lymphoma (TCL), which influences patient prognosis. A single-nucleotide polymorphism (SNP) rs3742330A>G has been identified in the Dicer gene, located in the 3' untranslated region (3' UTR) that is important for mRNA transcript stability. We investigated whether rs3742330 is associated with the survival in 163 TCL patients. Significant association between Dicer rs3742330 and TCL survival were found. Patients carrying the GG genotype (n = 12) had a significantly increased overall survival (OS) compared with those carrying the GA and AA genotypes (n = 70 and n = 81, respectively; p = 0.031). Moreover, the significant association was maintained for patients with mature T type (n = 134; p = 0.026). In multivariate Cox-regression analysis, rs3742330 proved to be an independent predictor for OS, together with the commonly used International Prognostic Index (IPI) and BAFF rs9514828, another SNP we have previously reported to be associated with TCL survival, with hazard ratios (HRs) for patient death rate of 8.956 (95% CI, 1.210 to 66.318; p = 0.032) for the GA genotype and 10.145 (95% CI, 1.371 to 75.084; p = 0.023) for the AA genotype. Furthermore, we observed cumulative effects of Dicer rs3742330 and BAFF rs9514828 on TCL survival. Compared with patients carrying zero unfavorable genotype, those carrying one and two unfavorable genotypes had an increased risk of death with a HR of 7.104 (95% CI, 0.969-53.086; p = 0.054) and 14.932 (95% CI, 1.950-114.354; p = 0.009), respectively, with a significant dose-response trend (p(trend) = 0.004). In conclusion, Dicer rs3742330 is associated with TCL survival, suggesting that genetic variation might play a role in predicting prognosis of TCL patients.
Dicer，一种 RNA 酶 III 家族的内切核酸酶，是 RNA 干扰 (RNAi) 途径所必需的。在包括某些 T 细胞淋巴瘤 (TCL) 亚型在内的各种癌症中已经发现 Dicer 的异常表达，这会影响患者的预后。在 Dicer 基因的 3'非翻译区 (3'UTR) 中发现了一个单核苷酸多态性 (SNP) rs3742330A>G，该 SNP 对于 mRNA 转录本的稳定性很重要。我们研究了 rs3742330 是否与 163 例 TCL 患者的生存有关。在 163 例 TCL 患者中，Dicer rs3742330 与 TCL 生存之间存在显著关联。与携带 GA 和 AA 基因型的患者相比（分别为 n=70 和 n=81），携带 GG 基因型（n=12）的患者总生存期 (OS) 显著延长（p=0.031）。此外，在成熟 T 型（n=134）患者中，这种显著关联仍然存在（p=0.026）。在多变量 Cox 回归分析中，rs3742330 与常用的国际预后指数 (IPI) 和 BAFF rs9514828 一起，被证明是 OS 的独立预测因子，这是我们之前报道过与 TCL 生存相关的另一个 SNP。GA 基因型患者的死亡风险比（HR）为 8.956（95%CI，1.210 至 66.318；p=0.032），AA 基因型患者的 HR 为 10.145（95%CI，1.371 至 75.084；p=0.023）。此外，我们观察到 Dicer rs3742330 和 BAFF rs9514828 对 TCL 生存的累积效应。与携带零个不利基因型的患者相比，携带一个和两个不利基因型的患者死亡风险增加，HR 分别为 7.104（95%CI，0.969-53.086；p=0.054）和 14.932（95%CI，1.950-114.354；p=0.009），且呈显著剂量反应趋势（p(trend)=0.004）。总之，Dicer rs3742330 与 TCL 生存相关，提示遗传变异可能在预测 TCL 患者预后方面发挥作用。
