淋巴毒素α和受体相互作用蛋白激酶 1 基因多态性可能与 R-CHOP 治疗弥漫性大 B 细胞淋巴瘤患者的预后相关。
Lymphotoxin alfa and receptor-interacting protein kinase 1 gene polymorphisms may correlate with prognosis in patients with diffuse large B cell lymphoma treated with R-CHOP.
机构信息
Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, 700-721, Korea.
出版信息
Cancer Chemother Pharmacol. 2010 Feb;65(3):571-7. doi: 10.1007/s00280-009-1066-x. Epub 2009 Jul 24.
PURPOSE
Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease entity due to diverse clinical outcomes to treatment. Most anticancer agents, regardless of their distinct mechanisms of action, ultimately kill cancer cells by inducing apoptosis. Accordingly, the present study analyzed the impact of polymorphisms of apoptosis-related genes on outcome in DLBCL patient treated with R-CHOP.
PATIENTS AND METHODS
Ninety patients with DLBCL treated with R-CHOP were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and 22 polymorphisms of 18 apoptosis-related genes were assessed using a polymerase chain reaction-restriction fragment length polymorphism assay.
RESULTS
All the evaluable patients were responsive to R-CHOP. The multivariate analysis showed that the AA genotype of lymphotoxin alpha (LTA) C804A (rs1041981) and GG genotype of RIPK1 G83A (rs2272990) were significantly correlated with a worse time to progression (TTP) compared with the combined C/A and C/C genotype and the combined G/A and A/A genotype (hazard ratio [HR]=7.92; 95% confidence interval [CI]=1.42-44.18; P=0.018 and HR=20.02; 95% CI=1.59-251.52; P value=0.018, respectively), whereas no association was observed between the other polymorphisms and TTP.
CONCLUSION
The polymorphisms of LTA (rs1041981) and RIPK1 (rs2272990) may correlate with TTP in patients with DLBCL treated with R-CHOP.
目的
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种异质性疾病实体，其治疗结果存在差异。大多数抗癌药物，无论其作用机制如何不同，最终都是通过诱导细胞凋亡来杀死癌细胞。因此，本研究分析了凋亡相关基因多态性对接受 R-CHOP 治疗的 DLBCL 患者结局的影响。
方法
本研究纳入了 90 例接受 R-CHOP 治疗的 DLBCL 患者。从石蜡包埋组织中提取基因组 DNA，并使用聚合酶链反应-限制性片段长度多态性分析评估 18 个凋亡相关基因的 22 个多态性。
结果
所有可评估的患者对 R-CHOP 均有反应。多变量分析显示，淋巴毒素α（LTA）C804A（rs1041981）的 AA 基因型和 RIPK1 G83A（rs2272990）的 GG 基因型与无进展时间（TTP）较差相关，与 C/A 和 C/C 基因型以及 C/A 和 A/A 基因型相比（风险比[HR]=7.92；95%置信区间[CI]：1.42-44.18；P=0.018 和 HR=20.02；95%CI：1.59-251.52；P 值=0.018），而其他多态性与 TTP 之间无相关性。
结论
LTA（rs1041981）和 RIPK1（rs2272990）的多态性可能与接受 R-CHOP 治疗的 DLBCL 患者的 TTP 相关。
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