Background: Chlorpyrifos and terbufos, two commonly used organophosphate insecticides, are classified as possibly carcinogenic (Group 2b) by the International Agency for Research on Cancer. Prior investigations of associations between chlorpyrifos and terbufos exposure and lung cancer in the Agricultural Health Study (AHS) have yielded inconsistent results, with a suggestion of higher lung cancer incidence in early studies, and more recently, null findings and one analysis in which 15-year lagged chlorpyrifos exposure was associated with lower incidence.
Objectives: To better understand these discordant results, we investigate whether occupational exposure to endotoxin, a bacterial component of organic dust that elicits a non-specific immune response, may modify observed associations between chlorpyrifos and terbufos and lung cancer incidence among restricted-use pesticide applicators in the AHS. We further examine histologic differences in associations.
Methods: Occupational exposures were reported by 52,205 applicators at the time of enrollment (1993-1997) to the AHS and in a follow-up interview conducted 5 years later. Incident lung cancer cases and tumor morphology were obtained from state cancer registries. We used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between occupational chlorpyrifos and terbufos exposure and incidence of total lung cancer, adenocarcinoma, and squamous cell carcinoma (SqCC) and assessed modification by endotoxin exposure.
Results: In total, 41,186 applicators (78.9%) were classified as endotoxin exposed.
Ever chlorpyrifos use was associated with lower lung cancer incidence for all applicators, RR = 0.80, 95%CI (0.74,0.88), null among endotoxin-unexposed, RR = 1.04, 95%CI (0.90,1.19), and lower for endotoxin-exposed applicators, RR = 0.68, 95%CI (0.60,0.76), p<0.0001. The association of ever terbufos use and lung cancer incidence was null for all applicators, RR = 0.95, 95%CI (0.86,1.04), positive among endotoxin-unexposed, RR=1.15, 95%CI (0.96,1.38), and lower among endotoxin-exposed applicators, RR = 0.73, 95%CI (0.64,0.83), p< 0.001.
Ever chlorpyrifos use was associated with lower adenocarcinoma incidence among all applicators, RR = 0.69, 95%CI (0.52,0.82), but higher incidence among endotoxin-unexposed, RR=1.35, 95%CI (1.01,1.81). Ever terbufos use was associated with SqCC, RR = 1.75, 95%CI (1.46,2.09); the association was of greater magnitude for endotoxin-unexposed, RR = 2.77, 95%CI (2.04,3.76), than endotoxin-exposed, RR = 1.30, 95%CI (1.01,1.67), p<0.0006.
Conclusions/Implications: Endotoxin exposure may modify associations of chlorpyrifos and terbufos exposure with lung cancer incidence, particularly incidence of adenocarcinoma and SqCC. Endotoxin exposure should be considered in studies of agricultural exposures and lung cancer incidence.