Objectives Explore quantitative exposure-response association for exposure to asbestos, crystalline silica, nickel, chromium and polycyclic aromatic hydrocarbons in the general population; further study effects on specific cell types and potential interaction with smoking and co-occurring occupational exposures.

Method Fourteen studies from Europe and Canada were pooled including 17 700 lung cancer cases and 21 800 controls with detailed information on tobacco habits and lifetime occupations. A quantitative job-exposure-matrix (SYN-JEM) was developed based on more than 350.000 exposure measurements from the participating countries. Different model specifications were compared to predict historical job-, time-, and region-specific exposure levels. Individual exposure levels were calculated for each subject by linking the SYN-JEM with the individual occupational histories. Unconditional logistic regression models were fitted to estimate odds ratios, 95% confidence intervals, and trends.

Results We observed exposure-response relationships with increasing duration and cumulative exposure for all agents and generally saw a stronger effect for squamous- and small cell lung carcinomas than for adenocarcinomas. Smoking and simultaneous exposure to other occupational exposures exerted a minor confounding effect on the risk estimates. The effect modifications with smoking tended to be supra-additive.

Conclusions SYNERGY adds valuable knowledge to the field of occupational cancer epidemiology, and underlines the importance to collect data on histology, and lifelong information on occupational exposures and smoking.