Atanaskovic Lavinika, Cikota-Aleksic Bojana, Tarabar Olivera, Trimcev Jovana, Zivanovic-Ivic Andelina, Marjanovic Slobodan, Magic Zvonko
Clinic for Hematology, Military Medical Academy, Belgrade, Serbia.
J BUON. 2016 Nov-Dec;21(6):1459-1465.
Polymorphic deletions in glutathione S-transferase (GST) genes are recognized as a risk factor for lymphoma, other hematological and non-hematological malignancies. The purpose of the present study was to investigate whether deletions of GSTT1 and GSTM1 as well as GSTP1 Ile- 105Val single nucleotide polymorphism influence clinical presentation, response to therapy and outcome in patients with diffuse large B-cell lymphoma (DLBCL).
The study included a total of 82 DLBCL patients treated with rituximab-CHOP (R-CHOP) therapy (6-8 cycles). GST genes were analyzed with PCR-based methodology.
The obtained frequencies of GSTT1 and GSTM1 null genotypes were 24 and 63%, respectively. The variant GSTP1 Val allele was present in 76% of the patients. No association between GST genotypes and clinical presentation was found. However, a higher frequency of GSTM1 null genotype was observed in patients who developed DLBCL before the age of 60 [odds ratio (OR) 3.12, 95% confidence interval (CI) 1.11-9.17; p=0.03]. Patients carrying at least one GSTP1 Val allele achieved remission in a shorter time period than patients with GSTP1 Ile/Ile genotype (p=0.05). GST genotypes didn't influence the incidence of relapse and survival. There were no toxic effects, life-threatening infections or significant delay in immunochemotherapy in the analyzed group of patients.
The present study showed the association of GSTM1 null genotype and DLBCL development before the age of 60 (prognostic cutoff). GST genotypes didn't influence survival, but patients with at least one low-producing GSTP1 Val allele achieved clinical remission in a shorter time period.
谷胱甘肽S-转移酶（GST）基因的多态性缺失被认为是淋巴瘤、其他血液系统和非血液系统恶性肿瘤的危险因素。本研究的目的是调查GSTT1和GSTM1基因缺失以及GSTP1 Ile-105Val单核苷酸多态性是否影响弥漫性大B细胞淋巴瘤（DLBCL）患者的临床表现、对治疗的反应和预后。
本研究共纳入82例接受利妥昔单抗-CHOP（R-CHOP）治疗（6-8个周期）的DLBCL患者。采用基于聚合酶链反应的方法分析GST基因。
GSTT1和GSTM1无效基因型的获得频率分别为24%和63%。76%的患者存在GSTP1 Val变异等位基因。未发现GST基因型与临床表现之间存在关联。然而，在60岁之前发生DLBCL的患者中，GSTM1无效基因型的频率更高[比值比（OR）3.12，95%置信区间（CI）1.11-9.17；p=0.03]。携带至少一个GSTP1 Val等位基因的患者比GSTP1 Ile/Ile基因型的患者缓解时间更短（p=0.05）。GST基因型不影响复发率和生存率。在分析的患者组中，没有出现毒性作用、危及生命的感染或免疫化疗的显著延迟。
本研究显示GSTM1无效基因型与60岁之前（预后临界值）DLBCL的发生有关。GST基因型不影响生存率，但携带至少一个低产GSTP1 Val等位基因的患者临床缓解时间更短。
