Exploring the joint effects of silicosis and smoking on lung cancer risks

Cigarette smoking and silicosis are potential causes of lung cancer among workers exposed to silica dust, but their joint effects are unclear. We explored the possible interactions between silicosis and smoking on lung cancer risks by summarizing data from the published literature. The standardized mortality ratio or standardized incidence ratio reported in each published report was first adjusted using "smoking adjustment factors" to correct for the biased estimation of the expected numbers of lung cancer among smokers and nonsmokers when using general population rates in the indirect standardization process. The ratio of the effect of silicosis on lung cancer risk among smokers to that among nonsmoker was calculated and named the "relative silicosis effect (RSE)". The synergy index was estimated to assess the additive interaction. Metaanalyses were used to obtain the weighed means of the RSE and synergy index. Ten cohort studies were reviewed and combined to yield a weighed RSE of 0.29 (95% CI: 0.20, 0.42), indicating negative risk-ratio multiplication between smoking and silicosis on the lung cancer risk. The combined weighed synergy index was 1.00 (95% CI: 0.79, 1.26), suggesting no departure from additivity. Sensitivity analyses showed that both estimates were quite robust. The independent risk-ratio effect of silicosis on lung cancer in smokers was about 30% of that in nonsmokers, and the joint effects of smoking and silicosis on the risk of lung cancer did not deviate from additivity and hence did not support biological synergism/antagonism.