Affiliations of authors: Infections and Immunoepidemiology Branch (MSS, AH, EAE, JK, AKC), Biostatistics Branch (RMP, HAK), and Genetic Epidemiology Branch (NEC), Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; HPV Immunology Laboratory, SAIC-Frederick Inc., Frederick, MD (TJK, GS, LAP); Department of Statistics, Dongguk University, Seoul, Korea (J-HP).
J Natl Cancer Inst. 2013 Dec 18;105(24):1871-80. doi: 10.1093/jnci/djt309. Epub 2013 Nov 18.
Despite growing recognition of an etiologic role for inflammation in lung carcinogenesis, few prospective epidemiologic studies have comprehensively investigated the association of circulating inflammation markers with lung cancer.
We conducted a nested case-control study (n = 526 lung cancer patients and n = 592 control subjects) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Control subjects were matched to lung cancer case patients on age, sex, follow-up time (median = 2.9 years), randomization year, and smoking (pack-years and time since quitting). Serum levels of 77 inflammation markers were measured using a Luminex bead-based assay. Conditional logistic regression and weighted Cox models were used to estimate odds ratios (ORs) and cumulative risks, respectively.
Of 68 evaluable markers, 11 were statistically significantly associated with lung cancer risk (P trend across marker categories < .05), including acute-phase proteins (C-reactive protein [CRP], serum amyloid A [SAA]), proinflammatory cytokines (soluble tumor necrosis factor receptor 2 [sTNFRII]), anti-inflammatory cytokines (interleukin 1 receptor antagonist [IL-1RA]), lymphoid differentiation cytokines (interleukin 7 [IL-7]), growth factors (transforming growth factor alpha [TGF-A]), and chemokines (epithelial neutrophil-activating peptide 78 [ENA 78/CXCL5], monokine induced by gamma interferon [MIG/CXCL9], B cell-attracting chemokine 1 [BCA-1/CXCL13], thymus activation regulated chemokine [TARC/CCL17], macrophage-derived chemokine [MDC/CCL22]). Elevated marker levels were associated with increased lung cancer risk, with odds ratios comparing the highest vs the lowest group ranging from 1.47 (IL-7) to 2.27 (CRP). For IL-1RA, elevated levels were associated with decreased lung cancer risk (OR = 0.71; 95% confidence interval = 0.51 to 1.00). Associations did not differ by smoking, lung cancer histology, or latency. A cross-validated inflammation score using four independent markers (CRP, BCA-1/CXCL13, MDC/CCL22, and IL-1RA) provided good separation in 10-year lung cancer cumulative risks among former smokers (quartile [Q] 1 = 1.1% vs Q4 = 3.1%) and current smokers (Q1 = 2.3% vs Q4 = 7.9%) even after adjustment for smoking.
Some circulating inflammation marker levels are associated with prospective lung cancer risk.
尽管炎症在肺癌发生中的病因作用已得到越来越多的认识，但很少有前瞻性的流行病学研究全面调查循环炎症标志物与肺癌之间的关联。
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嵌套病例对照研究（n=526 例肺癌患者和 n=592 例对照）。对照与肺癌病例患者按年龄、性别、随访时间（中位数=2.9 年）、随机化年份和吸烟情况（包年数和戒烟时间）匹配。使用 Luminex 珠基检测法测量了 77 种炎症标志物的血清水平。使用条件逻辑回归和加权 Cox 模型分别估计比值比（OR）和累积风险。
在 68 种可评估的标志物中，有 11 种与肺癌风险呈统计学显著相关（P 趋势<.05），包括急性期蛋白（C 反应蛋白[CRP]、血清淀粉样蛋白 A[SAA]）、促炎细胞因子（可溶性肿瘤坏死因子受体 2[sTNFRII]）、抗炎细胞因子（白细胞介素 1 受体拮抗剂[IL-1RA]）、淋巴样分化细胞因子（白细胞介素 7[IL-7]）、生长因子（转化生长因子 α[TGF-α]）和趋化因子（上皮中性粒细胞激活肽 78[ENA 78/CXCL5]、γ 干扰素诱导的单核细胞增多症[MIG/CXCL9]、B 细胞吸引趋化因子 1[BCA-1/CXCL13]、胸腺激活调节趋化因子[TARC/CCL17]、巨噬细胞衍生趋化因子[MDC/CCL22]）。标志物水平升高与肺癌风险增加相关，最高组与最低组比较的比值比范围为 1.47（IL-7）至 2.27（CRP）。对于 IL-1RA，升高的水平与肺癌风险降低相关（OR=0.71；95%置信区间=0.51 至 1.00）。关联不因吸烟、肺癌组织学或潜伏期而不同。使用四个独立标志物（CRP、BCA-1/CXCL13、MDC/CCL22 和 IL-1RA）的经过交叉验证的炎症评分可在戒烟者（四分位[Q]1=1.1% vs Q4=3.1%）和吸烟者（Q1=2.3% vs Q4=7.9%）的 10 年肺癌累积风险中进行很好的区分，即使在调整吸烟情况后也是如此。
一些循环炎症标志物水平与前瞻性肺癌风险相关。
