title: Meta-analyses of published epidemiological studies, 1979-2006, point to open causal questions in silica-silicosis-lung cancer research.
abstract: OBJECTIVE
  Following up on a previous meta-analysis of lung cancer risk in individuals without silicosis, we provide more detailed results of silica associated lung cancer risk in both silicotics and non-silicotics. The objective was to examine in depth whether current data allows to answer the pressing question "does silica cause lung cancer in the absence of silicosis"?
  
  
  METHODS
  We updated earlier meta-analyses of silicosis and lung cancer and compared the results with our 2009 meta-analysis of risks in individuals without silicosis. We performed fixed (FE) and random (RE) effects meta-analyses, calculated heterogeneity statistics, stratified the study material, performed sensitivity analyses with modified study results and meta-regressions to detect effect modification.
  
  
  RESULTS
  In silicotics, lung cancer risks were found to be doubled in 38 studies (FE: RR = 2.1; 95% CI = 2.0-2.3). In non-silicotics, eight studies without smoking adjustment suggested marginally elevated risks (FE: RR = 1.2; 95% CI = 1.1-1.3; RE: RR = 1.2; 95% CI =1.0-1.4) but three studies which were controlled for smoking showed null results (FE and RE: RR = 1.0; 95% CI = 0.8-1.3). Heterogeneity was substantial but could be linked to study characteristics, like sector of industry, and other second-level data in meta-regression. As no excess was observe dfor other smoking-related effects in studies ofllung cancer among non-silicotics, smoking was not considered to be an important confounder or modifier. CONCLUSIONn: Our meta-analyses further substantiate evidence of a strong association between silicosis and lung cancer. However, questions remain regarding lung cancer caused by silica in non-silicotics. Ideally, future investigations should consider the entire exposure-response range between silica exposure, silicosis development and lung cancer occurrence, and analyze data in terms of processes taking intermediate confounding into account.
authors.affiliation: Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University of Cologne, Germany. tim.erren@uni-koeln.de
authors.forename: T C
authors.initials: TC
authors.lastname: Erren
authors.forename: P
authors.initials: P
authors.lastname: Morfeld
authors.forename: Christine B
authors.initials: CB
authors.lastname: Glende
authors.forename: C
authors.initials: C
authors.lastname: Piekarski
authors.forename: P
authors.initials: P
authors.lastname: Cocco
mesh_terms: D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D015201:Meta-Analysis as Topic; D009784:Occupational Diseases / Q000453:epidemiology* / Q000209:etiology*; D012822:Silicon Dioxide / Q000009:adverse effects*; D012829:Silicosis / Q000150:complications* / Q000453:epidemiology* / Q000209:etiology
chemical_list: D012822:Silicon Dioxide