Abstract / Summary
Background: Compensation systems for asbestos-related lung cancer commonly apply the Helsinki criteria, which assume a 4% excess relative risk per fibre-year. Under linearity, the relative risk (RR) doubles at 25 fibre-years, where the probability of causation (PoC), estimated as (RR-1)/RR, reaches 50%. Recent large case-control studies suggest 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. PoC was estimated with 95% prediction intervals (95%PI) and interpreted as a lower bound. Results: Occupational cohort studies showed a shallow non-linear exposure-response relation at low exposure ranges (0-65 fibre-years) with substantial heterogeneity (I2 = 92.7%). SYNERGY showed a steeper relation with 6.8% (95%PI: 0% - 17.5%) 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 study, a high-quality study with harmonised exposure assessment, provided exposure-response estimates relevant to current exposure to lower levels of mixed asbestos fibres in the Netherlands, supporting lower exposure thresholds than the existing Helsinki criteria when estimating PoC in compensation contexts.