Ezennia Somayina C, Beane Freeman Laura E, Chang Vicky C, Xie Shuai, Sandler Dale P, Andreotti Gabriella, Parks Christine G, Friesen Melissa C, Hofmann Jonathan N
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, Maryland, USA
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, Maryland, USA.
Occup Environ Med. 2025 Feb 12;81(12):635-638. doi: 10.1136/oemed-2024-109646.
Occupational exposure to endotoxin has been associated with reduced lung cancer risk. The mechanisms underlying this association are unclear, though immunological alterations likely play a role. Farmers who perform certain tasks (eg, raising hogs) can be highly exposed to endotoxin. We, therefore, leveraged measurements of circulating immune markers from a prior investigation among male farmers in the Biomarkers of Exposure and Effect in Agriculture study to evaluate associations with newly developed estimates of endotoxin exposure.
Our investigation included 122 non-smoking farmers from Iowa, oversampling those raising hogs. Serum levels of 60 markers were measured using multiplex bead-based assays and ELISA. Based on an algorithm linking measurement-based task intensity estimates with self-reported task frequency, we estimated cumulative endotoxin exposure in the 30 days up to sample collection. We used multivariable linear regression to estimate geometric mean ratios of immune markers across exposure quartiles.
Higher endotoxin exposure in the last 30 days was associated with increased levels of fibroblast growth factor-2, macrophage inflammatory protein-3 alpha/CCL20 and sIL-4R (P≤0.02) and decreased levels of macrophage-derived chemokine/CCL22 (P=0.02). We also identified novel associations with several additional markers; those with the highest (vs lowest) exposure to endotoxin had decreased levels of TARC/CCL17, sCD27 and IL-1B.
Several circulating immune markers were associated with endotoxin levels in an exposure-response manner. Our findings are consistent with prior work on hog farming and suggest possible biological mechanisms through which endotoxin may confer a reduced risk of lung cancer.
职业性接触内毒素与肺癌风险降低有关。尽管免疫改变可能起作用，但这种关联的潜在机制尚不清楚。从事某些任务（如养猪）的农民可能会高度接触内毒素。因此，我们利用农业暴露与效应生物标志物研究中对男性农民先前调查的循环免疫标志物测量结果，来评估与新开发的内毒素暴露估计值之间的关联。
我们的调查包括来自爱荷华州的122名不吸烟农民，对养猪农民进行了过度抽样。使用基于多重微珠的检测方法和酶联免疫吸附测定法测量了60种标志物的血清水平。基于将基于测量的任务强度估计值与自我报告的任务频率联系起来的算法，我们估计了直至样本采集前30天的累积内毒素暴露量。我们使用多变量线性回归来估计各暴露四分位数中免疫标志物的几何平均比值。
过去30天内较高的内毒素暴露与成纤维细胞生长因子-2、巨噬细胞炎性蛋白-3α/CCL20和可溶性白细胞介素-4受体水平升高（P≤0.02）以及巨噬细胞衍生趋化因子/CCL22水平降低（P = 0.02）有关。我们还发现了与其他几种标志物的新关联；内毒素暴露最高（与最低相比）的人群中，胸腺活化调节趋化因子/CCL17、可溶性CD27和白细胞介素-1β水平降低。
几种循环免疫标志物与内毒素水平呈暴露反应关系。我们的研究结果与先前关于养猪业的研究一致，并提示了内毒素可能降低肺癌风险的潜在生物学机制。
