Kube Dieter, Hua Thanh-Duc, von Bonin Frederike, Schoof Nils, Zeynalova Samira, Klöss Marita, Gocht Daniela, Potthoff Bernd, Tzvetkov Mladen, Brockmöller Jürgen, Löffler Markus, Pfreundschuh Michael, Trümper Lorenz
Department of Hematology and Oncology and Pharmacology, Medical School of the Georg-August-University, Göttingen, Germany.
Clin Cancer Res. 2008 Jun 15;14(12):3777-84. doi: 10.1158/1078-0432.CCR-07-5182.
Current chemotherapy can achieve high response rates in aggressive non-Hodgkin's lymphoma (NHL), but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis whether interleukin-10 (IL-10) polymorphisms predict clinical outcome, leukocytopenia, or infectivity during therapy. IL-10 was chosen because immune alterations are a major risk factor for NHL, and IL-10 is a cytokine involved in inflammatory processes associated with clinical outcome.
Five hundred patients with aggressive NHL treated with CHOP/CHOEP were analyzed for IL-10 gene polymorphisms, including distal loci -7400InDel, -6752AT (rs6676671), and -6208CG (rs10494879) in comparison with proximal loci -3538AT (rs1800890), -1087AG (rs1800896), and -597AC (rs1800872) according to the incidence and outcome of the lymphoma.
No differences in allele frequencies or haplotypes were found comparing a cohort of patients with aggressive NHL/diffuse large B-cell lymphoma with a healthy control group. Patients with aggressive NHL characterized by IL-10(-7400DelDel) had shorter overall survival periods compared with the other genotypes (P = 0.004). The 3-year rate is 43.4% for IL-10(-7400DelDel) and 73.4% for IL-10(-7400InIn) and IL-10(-7400InDel) together. A significant increased risk for event-free survival is found for carriers of the genotype IL-10(-6752TT-6208CC-3538AA) (P = 0.047). Multivariate analysis of IL-10(-7400) gene variation in relation to overall survival adjusted to international prognostic index revealed a relative risk of 1.9 for carriers of IL-10(-7400DelDel) (P = 0.037). No associations were found analyzing diffuse large B-cell lymphoma patients separately.
Our results indicate that IL-10 gene variations could be associated to the clinical course of aggressive NHL, which points out the importance of host factors and respective genetic elements for treatment response.
当前化疗在侵袭性非霍奇金淋巴瘤（NHL）中可实现高缓解率，但影响肿瘤消退和生存的因素仍不明确。本探索性研究检验了白细胞介素-10（IL-10）基因多态性是否可预测治疗期间的临床结局、白细胞减少或感染性这一假设。选择IL-10进行研究是因为免疫改变是NHL的主要危险因素，且IL-10是一种参与与临床结局相关的炎症过程的细胞因子。
对500例接受CHOP/CHOEP治疗的侵袭性NHL患者进行IL-10基因多态性分析，包括远端位点-7400InDel、-6752AT（rs6676671）和-6208CG（rs10494879），并与近端位点-3538AT（rs1800890）、-1087AG（rs1800896）和-597AC（rs1800872）进行比较，同时根据淋巴瘤的发病率和结局进行分析。
将侵袭性NHL/弥漫性大B细胞淋巴瘤患者队列与健康对照组进行比较，未发现等位基因频率或单倍型存在差异。与其他基因型相比，具有IL-10（-7400DelDel）特征的侵袭性NHL患者总生存期较短（P = 0.004）。IL-10（-7400DelDel）的3年生存率为43.4%，IL-10（-7400InIn）和IL-10（-7400InDel）合并的3年生存率为73.4%。发现基因型IL-10（-6752TT-6208CC-3538AA）携带者无事件生存期风险显著增加（P = 0.047）。对与国际预后指数调整后的总生存期相关的IL-10（-7400）基因变异进行多变量分析，结果显示IL-10（-7400DelDel）携带者的相对风险为1.9（P = 0.037）。单独分析弥漫性大B细胞淋巴瘤患者未发现相关性。
我们的结果表明，IL-10基因变异可能与侵袭性NHL的临床病程相关，这指出了宿主因素和相关遗传因素对治疗反应的重要性。
