Probability of causation in individual workers: Lung cancer due to occupational exposure to asbestos

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 62.93 (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.