Increased Levels of Circulating Interleukin 6, Interleukin 8, C-Reactive Protein, and Risk of Lung Cancer
Increased Levels of Circulating Interleukin 6, Interleukin 8, C-Reactive Protein, and Risk of Lung Cancer
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DOI：
10.1093/jnci/djr216
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发表时间：
2011-07-01
影响因子：
10.3
通讯作者：
Harris, Curtis C.
中科院分区：
文献类型：
--
作者：
Pine, Sharon R.;Mechanic, Leah E.;Harris, Curtis C.
背景以前的研究主要基于少数患者，表明某些循环中的促炎细胞因子可能与肺癌有关;但是，在此情况下，方法分析270例肺癌患者和296例对照者血清白细胞介素6（IL-6）和白细胞介素8（IL-8）水平与肺癌的关系。在前瞻性前列腺、肺、结直肠和卵巢（PLCO）癌症筛查试验内的巢式病例对照研究中，在532例病例患者和595例对照受试者中验证结果。还分析了与全身炎症生物标志物C反应蛋白（CRP）的相关性。使用logistic回归模型评估生物标志物与肺癌之间的关联，该模型调整了吸烟、分期、组织学、年龄和性别。采用加权考克斯回归模型估计10年标准化肺癌绝对危险度。结果在NCI-MD研究中，血清IL-6和IL-8水平最高四分位数与肺癌相关（IL-6，比值比[OR] = 3.29，95%可信区间[CI] = 1.88 ~ 5.77; IL-8，OR = 2.06，95% CI = 1.19至3.57），并与PLCO研究中的肺癌风险相关（IL-6，OR = 1.48，95%CI = 1.04至2.10; IL-8，OR = 1.57，95%CI = 1.10至2.24）。在PLCO研究中，IL-6水平升高仅与采血后2年内诊断的肺癌相关，而IL-8水平升高与采血后2年以上诊断的肺癌相关（OR = 1.57，95%CI = 1.15至2.13）。在PLCO研究中，目前吸烟且IL-8和CRP水平较高的人群中，10年标准化肺癌绝对风险最高（绝对危险度= 8.01%，95%CI = 5.77%~ 11.05%）。结论血清IL-6、IL-8水平升高与肺癌的发生有关，只有IL-8水平与诊断前几年的肺癌风险有关。IL-8和CRP的组合在预测随后的肺癌方面比单独的任一标志物更稳健。J Natl Cancer Inst 2011;103：1112-1122
Background Previous studies that were based primarily on small numbers of patients suggested that certain circulating proinflammatory cytokines may be associated with lung cancer; however, large independent studies are lacking.Methods Associations between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and lung cancer were analyzed among 270 case patients and 296 control subjects participating in the National Cancer Institute-Maryland (NCI-MD) case-control study.Results were validated in 532 case patients and 595 control subjects in a nested case-control study within the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Association with C-reactive protein (CRP), a systemic inflammation biomarker, was also analyzed. Associations between biomarkers and lung cancer were estimated using logistic regression models adjusted for smoking, stage, histology, age, and sex. The 10-year standardized absolute risks of lung cancer were estimated using a weighted Cox regression model. Results Serum IL-6 and IL-8 levels in the highest quartile were associated with lung cancer in the NCI-MD study (IL-6, odds ratio [OR] = 3.29, 95% confidence interval [CI] = 1.88 to 5.77; IL-8, OR = 2.06, 95% CI = 1.19 to 3.57) and with lung cancer risk in the PLCO study (IL-6, OR = 1.48, 95% CI = 1.04 to 2.10; IL-8, OR = 1.57, 95% CI = 1.10 to 2.24), compared with the lowest quartile. In the PLCO study, increased IL-6 levels were only associated with lung cancer diagnosed within 2 years of blood collection, whereas increased IL-8 levels were associated with lung cancer diagnosed more than 2 years after blood collection (OR = 1.57, 95% CI = 1.15 to 2.13). The 10-year standardized absolute risks of lung cancer in the PLCO study were highest among current smokers with high IL-8 and CRP levels (absolute risk = 8.01%, 95% CI = 5.77% to 11.05%).Conclusions Although increased levels of both serum IL-6 and IL-8 are associated with lung cancer, only IL-8 levels are associated with lung cancer risk several years before diagnosis. Combination of IL-8 and CRP are more robust biomarkers than either marker alone in predicting subsequent lung cancer. J Natl Cancer Inst 2011;103:1112-1122