Prediagnostic serum levels of cytokines and other immune markers and risk of non-hodgkin lymphoma.
Prediagnostic serum levels of cytokines and other immune markers and risk of non-hodgkin lymphoma.
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DOI：
10.1158/0008-5472.can-11-0165
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发表时间：
2011-07-15
期刊：
影响因子：
11.2
通讯作者：
Rothman N
中科院分区：
文献类型：
--
作者：
Purdue MP;Lan Q;Bagni R;Hocking WG;Baris D;Reding DJ;Rothman N
虽然严重的免疫失调是非霍奇金淋巴瘤（NHL）的一个既定的危险因素，目前还不清楚亚临床免疫系统功能是否影响淋巴瘤的发生。为了解决这个问题，我们在前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中进行了一项巢式病例对照研究，以调查细胞因子和其他免疫标志物的循环水平是否与NHL的未来风险相关。检测了297例NHL患者和297例对照者的血清中细胞因子[白细胞介素（IL）-4、IL-6、IL-10、肿瘤坏死因子（TNF）-α]和其他免疫标志物[可溶性TNF受体1（sTNF-R1）、sTNF-R2、C反应蛋白（CRP）、sCD 27]。使用条件Logistic回归计算分析物浓度四分位数与NHL风险相关的比值比（OR）和95%置信区间（CI）。观察到血清sTNF-R1（四分位数4 vs.四分位数1：OR 1.7，95% CI 1.1-2.8; P趋势=0.02）和sCD 27（OR 5.3，95% CI 2.9-9.4; P趋势<0.0001）水平升高与NHL风险增加具有统计学显著相关性。这些相关性在采血后6年以上诊断病例的分析中仍然存在（sTNF-R1：OR 2.1，95% CI 1.0-4.0，Ptrend=0.01; sCD 27：OR 4.1，95% CI 1.9-8.5，Ptrend=0.0001）。IL-10、TNF-α和sTNF-R2水平升高也与NHL总体风险增加显著相关;然而，这些相关性随着从血液采集到病例诊断时间的增加而减弱，并且对于采集后6年以上诊断的病例为零。我们对sTNF-R1和sCD 27（分别为炎症和B细胞刺激状态的可能标志物）的研究结果支持亚临床炎症和慢性B细胞刺激在淋巴瘤发生中的作用。
While severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, tumor necrosis factor (TNF)-α] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein (CRP), sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. Odds ratios (OR) and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR 1.7, 95% CI 1.1–2.8; Ptrend=0.02) and sCD27 (OR 5.3, 95% CI 2.9–9.4; Ptrend<0.0001). These associations remained in analyses of cases diagnosed 6+ years following blood collection (sTNF-R1: OR 2.1, 95% CI 1.0–4.0, Ptrend=0.01; sCD27: OR 4.1, 95% CI 1.9–8.5, Ptrend=0.0001). Elevated levels of IL-10, TNF-α and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis, and were null for cases diagnosed 6+ years post-collection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis.