Diesel engine exhaust and lung cancer risks - evaluation of the meta-analysis by Vermeulen et al. 2014.
BACKGROUND
Vermeulen et al. 2014 published a meta-regression analysis of three relevant epidemiological US studies (Steenland et al. 1998, Garshick et al. 2012, Silverman et al. 2012) that estimated the association between occupational diesel engine exhaust (DEE) exposure and lung cancer mortality. The DEE exposure was measured as cumulative exposure to estimated respirable elemental carbon in μg/m(3)-years. Vermeulen et al. 2014 found a statistically significant dose-response association and described elevated lung cancer risks even at very low exposures.


METHODS
We performed an extended re-analysis using different modelling approaches (fixed and random effects regression analyses, Greenland/Longnecker method) and explored the impact of varying input data (modified coefficients of Garshick et al. 2012, results from Crump et al. 2015 replacing Silverman et al. 2012, modified analysis of Moehner et al. 2013).


RESULTS
We reproduced the individual and main meta-analytical results of Vermeulen et al. 2014. However, our analysis demonstrated a heterogeneity of the baseline relative risk levels between the three studies. This heterogeneity was reduced after the coefficients of Garshick et al. 2012 were modified while the dose coefficient dropped by an order of magnitude for this study and was far from being significant (P = 0.6). A (non-significant) threshold estimate for the cumulative DEE exposure was found at 150 μg/m(3)-years when extending the meta-analyses of the three studies by hockey-stick regression modelling (including the modified coefficients for Garshick et al. 2012). The data used by Vermeulen and colleagues led to the highest relative risk estimate across all sensitivity analyses performed. The lowest relative risk estimate was found after exclusion of the explorative study by Steenland et al. 1998 in a meta-regression analysis of Garshick et al. 2012 (modified), Silverman et al. 2012 (modified according to Crump et al. 2015) and Möhner et al. 2013. The meta-coefficient was estimated to be about 10-20 % of the main effect estimate in Vermeulen et al. 2014 in this analysis.


CONCLUSIONS
The findings of Vermeulen et al. 2014 should not be used without reservations in any risk assessments. This is particularly true for the low end of the exposure scale.
Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research of Cologne University, Kerpener Str. 62, 50937 Köln, Germany ; Institute for Occupational Epidemiology and Risk Assessment (IERA) of Evonik Industries AG, Rellinghauser Str. 1-11, D-45128 Essen, Germany.
Peter
P
Morfeld
Institute for Occupational, Social and Environmental Medicine of the Goethe University Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany ; European Research Group on Environment and Health in the Transport Sector (EUGT e.V.), Fritschestr. 35, 10627 Berlin, Germany.
Michael
M
Spallek
DEE; Diesel; Epidemiology; Lung cancer; Meta-analysis