Lung cancer risk and occupational pulmonary fibrosis: systematic review and meta-analysis

Abstract

Background: Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.

Research question: Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?

Study design and methods: A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.

Results: 52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.

Interpretation: This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.

FIGURE 1

Flow diagram of literature search, eligibility, and inclusion process according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

FIGURE 2

Risk-of-bias ratings for studies reporting on a) asbestos (n=21), b) silica (n=25) and c) mining (n=6). Criteria ratings served as the basis for the assignment of individual studies to one out of three study quality categories. ++: Definitely low risk of bias; +: probably low risk of bias; −: probably high risk of bias; − −: definitely high risk of bias; NR: not reported.

FIGURE 3

Meta-analysis with forest plots for the association of silicosis and lung cancer taken from studies reporting a) lung cancer rates in dead patients, e.g. in autopsies (OR_dead), and b) risk rates to die from lung cancer (OR_mortality). c) Meta-analysis with forest plot for the association of silicosis and lung cancer taken from studies with risk adjustment for smoking. df: degree of freedom; IV: inverse variance.