Sarcoidosis in Northern Ontario hard-rock miners: A case series.

Sarcoidosis is a rare multisystem granulomatous disease traditionally considered to be of unknown etiology. The notion that sarcoidosis has no known cause is called into question with the increasing number of case reports and epidemiologic studies showing associations between occupational exposures and disease published in the past 10-20 years. Occupational exposures for which associations are strongest and most consistent are silica and other inorganic dusts, World Trade Center (WTC) dust, and metals. Occupations identified as at-risk for sarcoidosis include construction workers; iron-foundry and diatomaceous earth workers; WTC emergency responders; and metal workers. We report here 12 cases of sarcoidosis in a cohort of hard-rock miners in Northern Ontario, Canada. To our knowledge sarcoidosis has not been reported previously in hard-rock miners. The cases are all male and Caucasian, with average age 74 years. At the time of diagnosis, two were never smokers; six, former smokers; and four, current smokers. Five have extrapulmonary sarcoidosis: two cardiac and three endocrine (hypercalciuria). Using occupational histories and air sampling data from the gold, uranium, and base-metal mines in which they worked, we examined exposure of each case to respirable crystalline silica (RCS). The annual mean RCS exposure for the 12 cases was 0.14 mg/m3 (range: 0.06-1.3 mg/m3 ); and the mean cumulative RCS exposure was 1.93 mg/m3  years (range: 0.64-4.03 mg/m3  years). We also considered their exposure to McIntyre Powder, an aluminum powder used for silicosis prophylaxis.

Sarcoidosis: An Occupational Disease?

Sarcoidosis is an important member of the family of granulomatous lung diseases. Since its recognition in the late 19th century, sarcoidosis has been thought of as a disease of unknown cause. Over the past 20 years, this paradigm has been shifting, more rapidly in the past 10 years. Epidemiologic studies, bolstered by case reports, have provided evidence of causal associations between occupational exposure to specific agents and sarcoidosis. Pathogenesis has been more clearly defined, including the role of gene-exposure interactions. The use of in vitro lymphocyte proliferation testing to detect sensitization to inorganic antigens is being examined in patients with sarcoidosis. These antigens include silica and certain metals. Results of studies to date show differences in immunoreactivity of occupationally exposed sarcoidosis cases compared with control cases, suggesting that lymphocyte proliferation testing may prove useful in diagnosing work-related disease. This review discusses recently published findings regarding associations between occupational exposure to silica and silicates, World Trade Center dust, and metals and risk for sarcoidosis, as well as advances in the development of diagnostic tools. Not all cases of sarcoidosis have an identified cause, but some do. Where the cause is occupational, its recognition is critical to enable effective treatment through removal of the affected worker from exposure and to inform intervention aimed at primary prevention.

Transcriptomic profiling of gamma ray induced mutants from the CGL1 human hybrid cell system reveals novel insights into the mechanisms of radiation-induced carcinogenesis.

BACKGROUND: Somatic cell hybrid systems generated by combining cancerous with non-cancerous cells provide useful model systems to study neoplastic transformation. Combined with recent advances in omics-based technologies, novel molecular signatures that drive radiation-induced carcinogenesis can be analyzed at an exceptional global level. METHODS: Here, we present a complete whole-transcriptome analysis of gamma-induced mutants (GIM) and gamma irradiated control (CON) segregants isolated from the CGL1 (HeLa x normal fibroblast) human hybrid cell-system exposed to high doses of radiation. Using the Human Transcriptome Array 2.0 microarray technology and conservative discrimination parameters, we have elucidated 1067 differentially expressed genes (DEGs) between tumorigenic and non-tumorigenic cells. RESULTS: Gene ontology enrichment analysis revealed that tumorigenic cells demonstrated shifts in extracellular matrix (ECM) and cellular adhesion profiles, dysregulation of cyclic AMP (cAMP) signaling, and alterations in nutrient transport and cellular energetics. Furthermore, putative upstream master regulator analysis demonstrated that loss of TGFß1 signaling due to reduced SMAD3 expression is involved in radiation-induced carcinogenesis. CONCLUSIONS: Taken together, this study presents novel insights into specific gene expression and pathway level differences that contribute to radiation-induced carcinogenesis in a human cell-based model. This global transcriptomic analysis and our published tumor suppressor gene deletion loci analyses will allow us to identify and functionally test candidate nexus upstream tumor suppressor genes that are deleted or silenced after exposure to radiation.

BEIR VI radon: The rest of the story.

The National Academy of Sciences (USA) conducted an extensive review on the health effects of radon (BEIR VI). This was a well written and researched report which had impact on regulations, laws and remediation of radon in homes. There were a number of problems with the interpretation of the report and three are focused on here. First, most of the radiation dose used to estimate risk was from homes with radon levels below the US Environmental Protection Agency's action level so that remediation had minor impact on total calculated attributable risk. Remediation of the high level homes (i.e., above the action level) would therefore have a minor impact on the calculated "population attributable risk". In individual homes with very high levels of radon, remediation may minimally reduce individual risk. Second, the conclusion communicated to the public, regulators and law makers was "Next to cigarette smoking radon is the second leading cause of lung cancer." This is not an accurate evaluation of the report. The correct conclusion would be: Next to cigarette smoking, high levels of radon combined with cigarette smoking is the second leading cause of lung cancer. In the never-smokers, few cancers could be attributable to radon. Thirdly, there is little question that high levels of radon exposure in mines combined with cigarette smoke and other significant insults in the mine environment produces excess lung cancer. However, the biological responses to low doses of radiation are different from those produced by high levels and low doses may result in unique protective responses (e.g. against smoking-related lung cancer). These three points will be discussed in detail. This paper shows that in contrary to the BEIR VI report, risk of lung cancer from residential radon is not increased and radon in homes appears to be helping to prevent smoking-related lung cancer. Thus, laws requiring remediation of homes for radon are providing little if any public health benefits.