Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
J Thorac Oncol. 2019 Jul;14(7):1192-1203. doi: 10.1016/j.jtho.2019.03.014. Epub 2019 Apr 3.
Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States. We and others have previously shown a relationship between immune and inflammation proteins with lung cancer in EAs. Our aim was to investigate the etiologic relationship between inflammation and lung cancer in AAs.
We adopted a two-stage, independent study design (discovery cases, n = 316; control cases, n = 509) (validation cases, n = 399; control cases, n = 400 controls) and measured 30 inflammation proteins in blood using Meso Scale Discovery V- PLEX multiplex assays.
We identified and validated 10 proteins associated with lung cancer in AAS, some that were common between EAs and AAs (C-reactive proteins [OR: 2.90; 95% confidence interval (CI): 1.99-4.22], interferon γ [OR: 1.55; 95% CI: 1.10-2.19], interleukin 6 [OR: 6.28; 95% CI: 4.10-9.63], interleukin 8 [OR: 2.76; 95% CI: 1.92-3.98]) and some that are only observed among AAs (interleukin 10 [OR: 1.69; 95% CI: 1.20-2.38], interleukin 15 [OR: 2.83; 95% CI: 1.96-4.07], interferon gamma-induced protein 10 [OR: 1.54; 95% CI: 1.09-2.18], monocyte chemotactic protein-4 [OR: 0.54; 95% CI: 0.38-0.76], macrophage inflammatory protein-1 alpha [OR: 1.57; 95% CI: 1.12-2.21], and tumor necrosis factor β [OR: 0.52; 95% CI: 0.37-0.74]). We did not find evidence that either menthol cigarette smoking or global genetic ancestry drove these population differences.
Our results highlight a distinct inflammation profile associated with lung cancer in AAs compared with EAs. These data provide new insight into the etiology of lung cancer in AAs. Further work is needed to understand what drives this relationship with lung cancer and whether these proteins have utility in the setting of early diagnosis.
与欧洲裔美国人(EAs)相比,非裔美国人(AAs)的肺癌发病率更高。我们和其他人之前已经证明了免疫和炎症蛋白与 EAs 中的肺癌之间存在关系。我们的目的是研究 AAs 中炎症与肺癌之间的病因关系。
我们采用了两阶段、独立的研究设计(发现病例,n=316;对照病例,n=509)(验证病例,n=399;对照病例,n=400 对照),并使用 Meso Scale Discovery V-PLEX 多重分析试剂盒测量血液中的 30 种炎症蛋白。
我们确定并验证了与 AAS 肺癌相关的 10 种蛋白,其中一些蛋白在 EAs 和 AAs 之间是共同的(C 反应蛋白[OR:2.90;95%置信区间(CI):1.99-4.22]、干扰素 γ[OR:1.55;95% CI:1.10-2.19]、白细胞介素 6[OR:6.28;95% CI:4.10-9.63]、白细胞介素 8[OR:2.76;95% CI:1.92-3.98]),而有些则仅在 AAs 中观察到(白细胞介素 10[OR:1.69;95% CI:1.20-2.38]、白细胞介素 15[OR:2.83;95% CI:1.96-4.07]、干扰素γ诱导蛋白 10[OR:1.54;95% CI:1.09-2.18]、单核细胞趋化蛋白-4[OR:0.54;95% CI:0.38-0.76]、巨噬细胞炎症蛋白-1α[OR:1.57;95% CI:1.12-2.21]和肿瘤坏死因子β[OR:0.52;95% CI:0.37-0.74])。我们没有发现薄荷香烟吸烟或全球遗传血统驱动这些人群差异的证据。
我们的结果突出了与 EAs 相比,AAs 肺癌相关的独特炎症特征。这些数据为 AAs 肺癌的病因学提供了新的见解。需要进一步研究以了解是什么驱动了这种与肺癌的关系,以及这些蛋白是否在早期诊断中有应用价值。