Meta-Analysis of Lung Cancer in Asphalt Roofing and Paving Workers with External Adjustment for Confounding by Coal Tar

Abstract

The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. Confidence intervals on adjusted RRs were estimated by the Monte Carlo methods outlined by Steenland and Greenland (2004). The meta-Relative Risk (meta-RR) and its variance were estimated by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chisquare and I 2 tests. Also explored were the influences of study design; differences between internally and externally adjusted RRs; and the potential impact of coal tar misclassification. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. The unadjusted meta-RR (random effects model) for the roofing studies was elevated (meta-RR = 1.67, 95% CI = 1.39-2.02, I 2 = 80%) and significantly greater than the meta-RR for the paving studies (meta-RR = 0.98, 95% CI = 0.81-1.18, I 2 = 59%). After adjustment for confounding by coal tar, however, the corrected roofers' meta-RR dropped to 1.10 (meta-RR = 1.10, 95% CI = 0.91-1.33, I 2 = 60%), while the corrected pavers' meta-RR was nearly unchanged at 0.96 (meta-RR = 0.96, 95% CI = 0.80-1.16, I 2 = 56%). Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Stratifying the roofing and paving studies by study design revealed that statistical heterogeneity was concentrated in the weaker designs such as those relying on death certificates for work history. When the weaker studies were excluded, the remaining roofing and paving studies had a combined meta-RR close to 1.0 (meta-RR = 1.01, 95% CI = 0. 88-1.17) with no significant heterogeneity (I 2 = 0%). Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.

Bayesian modelling of lung cancer risk and bitumen fume exposure adjusted for unmeasured confounding by smoking

“…As such, these assumptions are likely to inflate the bias factor. Similarly, a meta-analysis by Fayerweather33 addressing residual confounding by coal tar use also depended on the unrealistic assumptions about the exposure distributions as discussed in detail by Burstyn and Kromhout 34. This indicates that great care must be taken in defending assumptions used in sensitivity analysis, but it must be said in defence of quantitative sensitivity analyses that the transparent nature of assumptions they entail elevates the discussion of latent confounding from the realm of speculation to numerical analysis.…”

Hypothesis-based weight-of-evidence evaluation and risk assessment for naphthalene carcinogenesis

“… Lewis (2012) reviewed several studies of lung cancer risk in connection with industries and occupations in which naphthalene exposure is common, including the petroleum ( Wong and Raabe, 2000 ; Consonni et al 1999 ; Lewis et al 2003 ; Rushton, 1993 ), asphalt ( Boffetta et al 2003a , b ; Olsson et al 2010 ; Fayerweather 2007 ), and creosote industries ( Wong and Harris, 2005 ), and jet-fuel handlers ( D’Mello and Yamane, 2007 ; Yamane, 2006 ). No association with lung or nasal cancer was reported in any of the studies.…”

Primary and Secondary Emissions of VOCs and PAHs in Indoor Air from a Waterproof Coal-Tar Membrane: Diagnosis and Remediation

“…Normally, the coal-tar-based sealants contain more than >50,000 mg/kg of the 16 PAHs [ 26 , 30 ] that makes them potentially a source of toxic emission. The meta-analysis performed in [ 31 ] provided evidences supporting the hypothesis that the exposure to the combination of various coal tar-related PAHs can explain most if not all cases of lung cancer among workers of asphalt roofing and paving. Van Metre et al [ 32 ] carried out a quantitative study of PAH volatilization after application of coal-tar-based pavement.…”