Rationale: Millions of workers around the world are exposed to respirable crystalline
silica. Although
silica is a confirmed human lung
carcinogen, little is known regarding the
cancer risks associated with low levels of exposure and risks by
cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by
cancer subtype.Objectives: We aimed to address current knowledge gaps in
lung cancer risks associated with low levels of occupational
silica exposure and the joint effects of smoking and
silica exposure on
lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate
silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of
silica exposure and smoking on risk of
lung cancer. Stratified analyses by smoking history and
cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects.
Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative
silica exposure was associated (P trend < 0.01) with increasing
lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of
lung adenocarcinoma,
squamous cell carcinoma, and
small cell carcinoma. Supermultiplicative interaction of
silica exposure and smoking was observed on overall
lung cancer risks; superadditive effects were observed in risks of
lung cancer and all three included subtypes.Conclusions:
Silica exposure is associated with
lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking,
silicosis status, and
cancer subtype.