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A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships?

ABSTRACT: BACKGROUND: Asbestos is a well-recognized cause of lung cancer, but there is considerable between-study heterogeneity in the slope of the exposure-response relationship. OBJECTIVE: We considered the role of quality of the exposure assessment to potentially explain heterogeneity in exposure-response slope estimates. DATA SOURCES: We searched PubMed MEDLINE (1950-2009) for studies with quantitative estimates of cumulative asbestos exposure and lung cancer mortality and identified 19 original epidemiological studies. One was a population-based case-control study, and the others were industry-based cohort studies. DATA EXTRACTION: Cumulative exposure categories and corresponding risks were abstracted. Exposure-response slopes [KL (lung cancer potency factor of asbestos)] were calculated using linear relative risk regression models. DATA SYNTHESIS: We assessed the quality of five exposure assessment aspects of each study and conducted random effects univariate and multivariate meta-regressions. Heterogeneity in exposure-response relationships was greater than expected by chance (I2 = 64%). Stratification by exposure assessment characteristics revealed that studies with well-documented exposure assessment, larger contrast in exposure, greater coverage of the exposure history by exposure measurement data, and more complete job histories had higher meta-KL values than did studies without these characteristics. The latter two covariates were most strongly associated with the KL value. Meta-KL values increased when we incrementally restricted analyses to higher-quality studies. CONCLUSIONS: This meta-analysis indicates that studies with higher-quality asbestos exposure assessment yield higher meta-estimates of the lung cancer risk per unit of exposure. Potency differences for predominantly chrysotile versus amphibole asbestos-exposed cohorts become difficult to ascertain when meta-analyses are restricted to studies with fewer exposure assessment limitations.

SUBMITTER: Lenters V

PROVIDER: S-EPMC3226488 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships?

Lenters Virissa V Vermeulen Roel R Dogger Sies S Stayner Leslie L Portengen Lützen L Burdorf Alex A Heederik Dick D

Environmental health perspectives 20110627 11

<h4>Background</h4>Asbestos is a well-recognized cause of lung cancer, but there is considerable between-study heterogeneity in the slope of the exposure-response relationship.<h4>Objective</h4>We considered the role of quality of the exposure assessment to potentially explain heterogeneity in exposure-response slope estimates.<h4>Data sources</h4>We searched PubMed MEDLINE (1950-2009) for studies with quantitative estimates of cumulative asbestos exposure and lung cancer mortality and identifie ...[more]

PMID: 21708512

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Project description:BackgroundStudies on asbestos-induced tumourigenesis have indicated the role of, e.g., reactive oxygen/nitrogen species, mitochondria, as well as NF-kappaB and MAPK signalling pathways. The exact molecular mechanisms contributing to asbestos-mediated carcinogenesis are, however, still to be characterized.MethodsIn this study, gene expression data analyses together with gene annotation data from the Gene Ontology (GO) database were utilized to identify pathways that are differentially regulated in lung and tumour tissues between asbestos-exposed and non-exposed lung cancer patients. Differentially regulated pathways were identified from gene expression data from 14 asbestos-exposed and 14 non-exposed lung cancer patients using custom-made software and Iterative Group Analysis (iGA). Western blotting was used to further characterize the findings, specifically to determine the protein levels of UBA1 and UBA7.ResultsDifferences between asbestos-related and non-related lung tumours were detected in pathways associated with, e.g., ion transport, NF-kappaB signalling, DNA repair, as well as spliceosome and nucleosome complexes. A notable fraction of the pathways down-regulated in both normal and tumour tissue of the asbestos-exposed patients were related to protein ubiquitination, a versatile process regulating, for instance, DNA repair, cell cycle, and apoptosis, and thus being also a significant contributor of carcinogenesis. Even though UBA1 or UBA7, the early enzymes involved in protein ubiquitination and ubiquitin-like regulation of target proteins, did not underlie the exposure-related deregulation of ubiquitination, a difference was detected in the UBA1 and UBA7 levels between squamous cell carcinomas and respective normal lung tissue (p = 0.02 and p = 0.01) without regard to exposure status.ConclusionOur results indicate alterations in protein ubiquitination related both to cancer type and asbestos. We present for the first time pathway analysis results on asbestos-associated lung cancer, providing important insight into the most relevant targets for future research.

Project description:CONTEXT: A detailed evaluation of the correlation and linearity of industrial hygiene retrospective exposure assessment (REA) for cumulative asbestos exposure with asbestos lung burden analysis (LBA) has not been previously performed, but both methods are utilized for case-control and cohort studies and other applications such as setting occupational exposure limits. OBJECTIVE: (a) To correlate REA with asbestos LBA for a large number of cases from varied industries and exposure scenarios; (b) to evaluate the linearity, precision, and applicability of both industrial hygiene exposure reconstruction and LBA; and (c) to demonstrate validation methods for REA. METHODS: A panel of four experienced industrial hygiene raters independently estimated the cumulative asbestos exposure for 363 cases with limited exposure details in which asbestos LBA had been independently determined. LBA for asbestos bodies was performed by a pathologist by both light microscopy and scanning electron microscopy (SEM) and free asbestos fibers by SEM. Precision, reliability, correlation and linearity were evaluated via intraclass correlation, regression analysis and analysis of covariance. Plaintiff's answers to interrogatories, work history sheets, work summaries or plaintiff's discovery depositions that were obtained in court cases involving asbestos were utilized by the pathologist to provide a summarized brief asbestos exposure and work history for each of the 363 cases. RESULTS: Linear relationships between REA and LBA were found when adjustment was made for asbestos fiber-type exposure differences. Significant correlation between REA and LBA was found with amphibole asbestos lung burden and mixed fiber-types, but not with chrysotile. The intraclass correlation coefficients (ICC) for the precision of the industrial hygiene rater cumulative asbestos exposure estimates and the precision of repeated laboratory analysis were found to be in the excellent range. The ICC estimates were performed independent of specific asbestos fiber-type. CONCLUSIONS: Both REA and pathology assessment are reliable and complementary predictive methods to characterize asbestos exposures. Correlation analysis between the two methods effectively validates both REA methodology and LBA procedures within the determined precision, particularly for cumulative amphibole asbestos exposures since chrysotile fibers, for the most part, are not retained in the lung for an extended period of time.

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A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships?

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A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships?

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