Lützen Portengen

Background: Occupational epidemiological analyses typically focus on a priori hypotheses relating disease to specific exposures or occupations. We used regularized regression models to agnostically identify occupations associated with lung cancer while accounting for known lung carcinogens. Methods: We pooled data from 14 European and Canadian lung cancer case–control studies. The main analysis included 13 587 cases and 16 410 controls for men and 3199 cases and 4408 controls for women. Associations between ever-employment in various occupations and lung cancer risks were evaluated using two selection approaches: a least absolute shrinkage and selection operator regression and a two-stage Bayesian hierarchical horseshoe model accounting for age, study, smoking, and occupational exposure to known lung carcinogens. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for selected occupations. Results: For men, occupations consistently identified as positively associated with lung cancer included miners (OR = 1.28, 95% CI: 1.06–1.54) and bricklayers (OR = 1.30, 95% CI: 1.12–1.52), while secondary education teachers (OR = 0.37, 95% CI: 0.22–0.60), production managers (OR = 0.66, 95% CI: 0.54–0.81), and government executive officials (OR = 0.72, 95% CI: 0.62–0.83) were negatively associated. For women, secondary language and literature teachers (OR = 0.39, 95% CI: 0.20–0.72) and government executive officials (OR = 0.63, 95% CI: 0.48–0.81) showed negative associations. Conclusion: Two agnostic, data-driven models identified several occupations associated with both increased and decreased lung cancer risks. These associations persisted after accounting for known exposures and covariates, highlighting the need to investigate unidentified occupational factors.

Background: Lung cancer compensation systems for occupational exposure to asbestos commonly apply Helsinki criteria, which assume 4% excess lung cancer risk per fibre-year of asbestos exposure. The ′Probability of Causation (PoC)′ is ≥50% at 25 fibre-years (risk doubling threshold). Large case-control studies have suggested steeper exposure-response relations at lower exposures. We aimed to estimate PoC of asbestos-related lung cancer to evaluate exposure thresholds for compensation of lung cancer cases occupationally exposed to asbestos. Methods: Relative risk of asbestos-related lung cancer was estimated using two approaches: » A meta-regression of 22 occupational studies forming the core evidence on cumulative asbestos exposure and lung cancer since the 1980s (130,341 participants). » A meta-analysis of the recently conducted SYNERGY pooled case-control study (14 studies, 37,866 participants), adjusted for age, sex, smoking, and study. The likelihood that lung cancer was caused by asbestos was estimated as the PoC with 95% prediction intervals (95%PI). Results: Occupational cohort studies produced a shallow exposure-response relation with substantial heterogeneity (I² = 92.7%). SYNERGY showed a steeper relation with 6.8% (95%PI: 0% – 17.7%) lung cancer risk increase per fibre-year and lower heterogeneity (I² = 63.4%). PoC ≥50% occurred at 62.9 (point estimate) and 18.2 fibre-years (upper 95%PI) for occupational asbestos studies, compared to 10.5 and 4.3, respectively, in SYNERGY. Conclusions: The SYNERGY pooled case-control study provided exposure-response estimates that are more representative of current exposure to lower mixed asbestos fibres in the Netherlands, supporting lower exposure thresholds than the existing Helsinki criteria when estimating PoC in compensation contexts.

Supplementary Data from Estimation of the Exposure–Response Relation between Benzene and Acute Myeloid Leukemia by Combining Epidemiologic, Human Biomarker, and Animal Data

Supplementary Data from Estimation of the Exposure–Response Relation between Benzene and Acute Myeloid Leukemia by Combining Epidemiologic, Human Biomarker, and Animal Data