Objective The Synergy project derived quantitative exposure-response associations for five occupational lung carcinogens (asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons, and respirable crystalline silica) and lung cancer in a pooled analysis of population based case-control studies. Considering a proportion of workers were exposed to more than one of these carcinogens, a joint effect on lung cancer risk is possible.

Methods We estimated joint effects by including an interaction term between two occupational carcinogens in the logistic regression models that were developed for the Synergy project. Analyses were conducted with either both exposures dichotomized (ever vs. never exposed), or with one exposure on a continuous scale (cumulative exposure), and the other dichotomized. Analyses were conducted for all lung cancer subtypes combined and stratified by subtype. We applied a Bonferroni correction.

Results We observed a negative interaction between occupational exposure to nickel and asbestos. The interaction effect was largest for the subtype of squamous cell carcinoma: ratio of odds ratios: 0.76 (95% CI 0.65–0.88), odds ratio of the joint effect: 1.40 (95% CI 1.26–1.56). No other interaction effects were statistically significant after correction for multiple testing. Analyses in which one of the exposures was included on a continuous scale resulted in similar results.

Conclusion We observed little evidence for a statistical multiplicative interaction between most of the occupational carcinogens. The negative multiplicative interaction between asbestos and nickel was not explained by a high correlation between these exposures. Ignoring specific study specific matching criteria might have introduced some bias in the results.