Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands.
Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1577-84. doi: 10.1158/1055-9965.EPI-09-1237. Epub 2010 May 25.
Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general population.
Using bead-based immunoassays, plasma levels of 11 cytokines, 4 chemokines, and 1 adhesion molecules were measured in prediagnostic blood samples of 86 NHL cases and 86 matched controls (average time between blood collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for body mass index and alcohol consumption was used to analyze the association between individual plasma cytokine levels and the risk of developing NHL.
In multivariate models, excluding cases diagnosed within 2 years after inclusion, we observed a significant association for interleukin 2 (IL2; P trend = 0.004), interferon (IFN)-gamma (P trend = 0.05), and intercellular adhesion molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a significant association with IL2 (P trend = 0.003), tumor necrosis factor-alpha (TNF-alpha; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association with IL5 (P trend = 0.07) and IFN-gamma (P trend = 0.08).
The results of this study suggest, in a prospective setting, a possible association between plasma levels of IL2, ICAM, IFN-gamma, and TNF-alpha with NHL risk and provide some evidence that risk of NHL might be related to a downregulation of T helper 1 cytokines.
Identification of subtle changes in immune response regulation quantified by plasma cytokine levels possibly provides new insights in the etiology of NHL.
最近，人们研究了与免疫系统相关的生物标志物，如细胞因子，以进一步了解非霍奇金淋巴瘤（NHL）的病因。然而，迄今为止，尚无研究前瞻性地研究细胞因子水平与普通人群中 NHL 风险的关系。
使用基于珠的免疫测定法，在 86 例 NHL 病例和 86 例匹配对照者的前瞻性血样中测量了 11 种细胞因子、4 种趋化因子和 1 种黏附分子的血浆水平（采血与诊断之间的平均时间为 4.5 年）。采用条件逻辑回归分析，调整体重指数和饮酒因素后，分析个体血浆细胞因子水平与 NHL 发病风险的关系。
在多变量模型中，排除了纳入后 2 年内诊断的病例，我们观察到白细胞介素 2（IL2；P 趋势=0.004）、干扰素（IFN）-γ（P 趋势=0.05）和细胞间黏附分子（ICAM；P 趋势=0.04）与 NHL 风险呈显著相关。B 细胞 NHL 患者的亚分析显示，IL2（P 趋势=0.003）、肿瘤坏死因子-α（TNF-α；P 趋势=0.03）和 ICAM（P 趋势=0.04）与 NHL 风险呈显著相关，IL5（P 趋势=0.07）和 IFN-γ（P 趋势=0.08）与 NHL 风险呈边缘相关。
本研究结果提示，在前瞻性研究中，IL2、ICAM、IFN-γ 和 TNF-α 的血浆水平与 NHL 风险之间可能存在关联，并提供了一些证据，表明 NHL 的风险可能与 Th1 细胞因子的下调有关。
通过血浆细胞因子水平定量检测免疫反应调节的细微变化，可能为 NHL 的病因学提供新的见解。
