Exposure Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies in Europe and Canada

Ann OLSSON, International Agency for Research on Cancer, France
VERMEULEN R. 3 , SCHÜZ J. 1 , PESCH B. 4 , PETERS S. 5 , BEHRENS T. 4 , PORTENGEN L. 3 , MIRABELLI D. 6 , GUSTAVSSON P. 2 , CONSONNI D. 7 , JÖCKEL K. 8 , KROMHOUT H. 3 , BRÜNING T. 4 , STRAIF K. 1 , ON BEHALF OF T. 1

1 Environment and Radiation, International Agency for Research on Cancer, Lyon, France
2 The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
3 Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht, the Netherlands
4 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance – Institute of the Ruhr-Universität Bochum (IPA), Nochum, Germany
5 Occupational Respiratory Epidemiology, School of Population Health, University of Western Australia, Perth, Australia
6 Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piemonte, Turin, Italy
7 Epidemiology Unit, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Milan, Italy
8 Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany

Background: The evidence is limited regarding risk and the shape of the exposure-response curve at low levels of asbestos exposure. We estimated the exposure-response for occupational exposure to asbestos and assessed the joint effect of asbestos exposure and smoking by sex, and lung cancer subtypes (adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma) in general population studies.
Methods: Fourteen case-control studies conducted between 1985 and 2010 from Europe and Canada were pooled, including 16,901 lung cancer cases (13,605 men, 3296 women) and 20,965 controls (16451 men, 4514 women) with detailed information on tobacco habits and lifetime occupations. A quantitative job-exposure-matrix (SYN-JEM) was developed to estimate job-, time period-, and region-specific exposure levels. Fiber years (ff/ml-years) were calculated for each subject by linking SYN-JEM with individual occupational histories. Unconditional logistic regression models were fitted to estimate odds ratios (OR), 95% confidence intervals (CI), and trends.
Results: The OR for the highest quartile of cumulative asbestos exposure (>2.8 ff/ml-years) was 1.38 (95%CI 1.27-1.50) in men and 1.22 (95% CI 0.84-1.78) in women. In men, increasing lung cancer risk was observed with increasing exposure to asbestos in all smoking categories; and for all major subtypes of lung cancer. In women, the asbestos related lung cancer risk was increased for all subtypes in current smokers with ORs approximately 2-fold. The interaction between asbestos exposure and smoking was more than additive among men and women for all lung cancer types, although not statistically significant for all combinations of subtype and gender; moreover the interaction between asbestos and smoking among men did not significantly deviate from multiplicativity.
Conclusions: Our results in men showed an excess risk of lung cancer and its subtypes at low levels of cumulative exposure, with an exposure-response slope steeper in this exposure range than at higher previously studied levels.