A reduced risk of lung cancer has been observed among farmers with increasing numbers of livestock (mainly hogs) in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. This association may be attributable to exposure to endotoxin, a component of the cell wall of gram-negative bacteria that is consistently associated with decreased lung cancer risk in both agricultural and non-agricultural settings. Levels of endotoxin and other bioaerosols are particularly high in hog farming. Therefore, to characterise potential biologic mechanisms underlying the inverse association with lung cancer and explore other immunologic changes associated with these exposures, we measured serum immune marker levels using a multiplexed bead-based assay in 61 active hog farmers and 61 matched controls. Both groups were selected from non-smoking male Iowans in the study of Biomarkers of Exposure and Effect in Agriculture, a molecular epidemiologic study within the AHS. We compared natural log-transformed analyte levels between hog farmers and controls using multivariate linear regression models adjusted for age, season, body mass index, recent infections, recent use of anti-inflammatory medications, and exposure to other animals. Relative to controls, hog farmers had a 17% decrease (95% confidence interval [CI]: −4% to −28%) in circulating levels of macrophage-derived chemokine (MDC/CCL22), a chemokine of particular interest a priori because high levels have been prospectively linked to an increased risk of lung cancer. Levels of other markers were elevated among hog farmers, including macrophage inflammatory protein-3 alpha (MIP-3α; 111% increase, 95% CI: 19% to 273%), basic fibroblast growth factor (FGF-2; 95% increase, 11% to 242%), and soluble interleukin-4 receptor (sIL-4R; 12% increase, 1% to 25%). These results provide insights into potential immunomodulatory mechanisms through which endotoxin or other bioaerosol exposures associated with hog farming may influence lung cancer risk, and warrant further investigation with more detailed bioaerosol exposure assessment.
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