Dataset Information

Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.

ABSTRACT:

Objective

Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.

Methods

We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.

Results

A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ?30 years, and the shipbuilding industry presented a significant eRR given a latency ?40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.

Conclusions

This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.

SUBMITTER: Lee LJ

PROVIDER: S-EPMC6303649 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.

Lee Lukas Jyuhn-Hsiarn LJ Lin Cheng-Kuan CK Pan Chih-Hong CH Cheng Yawen Y Chang Yu-Yin YY Liou Saou-Hsing SH Wang Jung-Der JD

BMJ open 20181209 12

<h4>Objective</h4>Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.<h4>Methods</h4>We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed fo ...[more]

PMID: 30530573

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Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.

Project description:BackgroundMalignant pleural mesothelioma (MM) is an aggressive, asbestos-related pulmonary cancer that is increasing in incidence. Because diagnosis is difficult and the disease is relatively rare, most patients present at a clinically advanced stage where possibility of cure is minimal. To improve surveillance and detection of MM in the high-risk population, we completed a series of clinical studies to develop a noninvasive test for early detection.Methodology/principal findingsWe conducted multi-center case-control studies in serum from 117 MM cases and 142 asbestos-exposed control individuals. Biomarker discovery, verification, and validation were performed using SOMAmer proteomic technology, which simultaneously measures over 1000 proteins in unfractionated biologic samples. Using univariate and multivariate approaches we discovered 64 candidate protein biomarkers and derived a 13-marker random forest classifier with an AUC of 0.99±0.01 in training, 0.98±0.04 in independent blinded verification and 0.95±0.04 in blinded validation studies. Sensitivity and specificity at our pre-specified decision threshold were 97%/92% in training and 90%/95% in blinded verification. This classifier accuracy was maintained in a second blinded validation set with a sensitivity/specificity of 90%/89% and combined accuracy of 92%. Sensitivity correlated with pathologic stage; 77% of Stage I, 93% of Stage II, 96% of Stage III and 96% of Stage IV cases were detected. An alternative decision threshold in the validation study yielding 98% specificity would still detect 60% of MM cases. In a paired sample set the classifier AUC of 0.99 and 91%/94% sensitivity/specificity was superior to that of mesothelin with an AUC of 0.82 and 66%/88% sensitivity/specificity. The candidate biomarker panel consists of both inflammatory and proliferative proteins, processes strongly associated with asbestos-induced malignancy.SignificanceThe SOMAmer biomarker panel discovered and validated in these studies provides a solid foundation for surveillance and diagnosis of MM in those at highest risk for this disease.

Dataset Information

Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.

Objective

Methods

Results

Conclusions

Publications

Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.

Similar Datasets

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