[肿瘤坏死因子-α基因多态性对沙利度胺方案治疗多发性骨髓瘤疗效的影响]

[Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma].

作者信息

DU Juan, Yuan Zhen-Gang, Zhang Chun-Yang, Fu Wei-Jun, Jiang Hua, Chen Bao-An, Hou Jian

机构信息

Southeast University Medical School, Nanjing 210009, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2009 Oct;30(10):649-53.

PMID:19954656

Abstract

OBJECTIVE

To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM).

METHODS

The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis.

RESULTS

In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049).

CONCLUSION

The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

摘要

目的

评估肿瘤坏死因子-α（TNF-α）启动子区域-238和-308位点的多态性对沙利度胺（Thal）方案治疗多发性骨髓瘤（MM）临床疗效的影响。

方法

采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对168例接受Thal方案治疗的MM患者TNF-α启动子区域-238和-308位点的多态性进行检测。通过逻辑回归分析基因型与总缓解率的相关性，并采用单因素和多因素分析评估生存率。

结果

在TNF-α -238位点，11例（6.5%）患者为GA基因型，1例（0.6%）为AA基因型。在TNF-α -308位点，19例（11.3%）为GA基因型，1例（0.6%）为AA基因型。单因素分析显示，TNF-α -238 GA + AA基因型与无进展生存期（PFS）显著延长相关（P = 0.017），总生存期（OS）较好（P = 0.150）。多因素COX回归分析表明，TNF-α -238多态性状态是PFS延长的独立预后因素（P = 0.049）。