Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crystalline silica was recently classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, the direct genotoxic effect of silica in humans remains unclear. We examined the p53 and K-ras gene mutations in lung cancer in workers with silicosis (LCWS). DNA was extracted from paraffin-embedded tissues and examined by PCR-RFLP, PCR-SSCP, and DNA sequencing. The mutation frequencies of p53 gene were high, but the mutation distributions in exons and among the histological types of LCWS differed from those of common (i.e., not silicosis-related) lung cancer. Furthermore, no mutations in codon 12 of K-ras gene (predominant in common lung cancer) were found in LCWS. These findings in the mutational spectrum support a carcinogenic effect of silica dust at the DNA molecular level.
 ...
PMID:A distinct mutational spectrum of p53 and K-ras genes in lung cancer of workers with silicosis. 1090 1

The eastern part of the Toyama Prefecture in Japan is one of the high-incidence areas of silicosis due to tunnel construction. In 1977 and 1978, we conducted a questionnaire survey primarily concerning the occupational history of all male inhabitants over 30 years of age living in five villages in this area and found 603 tunnel workers and inhabitants without dust history. These workers have been followed up to 1994 for about 17 to 18 years to clarify the relationship between tunnel work and lung cancer mortality. The SMR's of workers with dust exposure for all causes and for lung cancer was 120 and 188, respectively, which was significantly higher than those of the Japanese general population. After adjustment for age and smoking habits using Cox's proportional hazard model, tunnel work showed a significant relationship to mortality. Mortality risk ratio of tunnel workers was 2.15 compared with that of inhabitants without dust exposure history.
 ...
PMID:Dust exposure and lung cancer mortality in tunnel workers. 1090 15

The relationship between crystalline silica and lung cancer has been the subject of many recent publications, conferences, and regulatory considerations. An influential, international body has determined that there was sufficient evidence to conclude that quartz and cristobalite are carcinogenic in humans. The present authors believe that the results of these studies are inconsistent and, when positive, only weakly positive. Other, methodologically strong, negative studies have not been considered, and several studies viewed as providing evidence supporting the carcinogenicity of silica have significant methodological weaknesses. Silica is not directly genotoxic and is a pulmonary carcinogen only in the rat, a species that seems to be inappropriate for assessing particulate carcinogenesis in humans. Data on humans demonstrate a lack of association between lung cancer and exposure to crystalline silica. Exposure-response relationships have generally not been found. Studies in which silicotic patients were not identified from compensation registries and in which enumeration was complete did not support a causal association between silicosis and lung cancer, which further argues against the carcinogenicity of crystalline silica.
 ...
PMID:Silica, silicosis, and lung cancer: a response to a recent working group report. 1128 67

The 'Sendzimir' Steel Mill, Cracow, Poland, gives employment to approximately 17,000 workers. During the years 1994-98, 1396 compensation claims for diseases related to occupational hazards were registered. After a scrupulous investigation, 851 cases were certified as occupation-related diseases. Of this number, 481 cases (56.5%) were diagnosed as pulmonary diseases, including silicosis (n = 225, 46.7%); chronic bronchitis (n = 138, 28.7%); lung carcinoma (n = 59, 12.3%); epithelial cancer (n = 42); adenocarcinoma (n = 12); microcellular carcinoma (n = 5); asthma, 12 atopic and 24 non-atopic (n = 36, 7.5%); and asbestosis (n = 23, 4.8%). Chronic bronchitis was diagnosed in patients exposed to industrial dusts, containing SiO2, NOx, and SO2. Asthma occurred most frequently among those exposed mainly to Cr+6, Co and Ni containing dusts, and lung carcinoma in those exposed to policyclic aromatic hydrocarbons, including benz(a)pyren, asbestos, chromium, vapours of oils and lubricants. In 1994-96, chronic bronchitis and silicosis, and in 1997-98, lung carcinoma and asthma were most frequently diagnosed in the workers under study. It is likely that the diminishing frequency of chronic bronchitis and silicosis was the consequence of technological progress, and greater concern for hygiene standards. Increasing incidence of lung cancer reflects long latency characteristic of this illness.
 ...
PMID:Occurrence of pulmonary diseases in steel mill workers. 1096 40

In 1997, the International Agency for Research on Cancer determined that crystalline silica was a human carcinogen but noted inconsistencies in the epidemiology. There are few exposure-response analyses. The authors examined lung cancer mortality among 4,626 industrial sand workers, estimating exposure via a job-exposure matrix based on 4,269 industrial hygiene samples collected in 1974--1995. The average length of employment was 9 years, and estimated average exposure was 0.05 mg/m(3) (the National Institute of Occupational Safety and Health Recommended Exposure Limit). Results confirmed excess mortality from silicosis/pneumoconioses (standardized mortality ratio = 18.2, 95% confidence interval: 10.6, 29.1; 17 deaths). The lung cancer standardized mortality ratio was 1.60 (95% confidence interval: 1.31, 1.93; 109 deaths). Limited data suggested that smoking might account for 10--20% of the lung cancer excess. Exposure-response analyses by quartile of cumulative exposure (15-year lag) yielded standardized rate ratios of 1.00, 0.78, 1.51, and 1.57 (p for trend = 0.07). Nested case-control analyses after exclusion of short-term workers, who had high overall morality, yielded odds ratios by quartile of cumulative exposure (15-year lag) of 1.00, 1.35, 1.63, and 2.00 (p for trend = 0.08) and odds ratios by quartile of average exposure of 1.00, 0.92, 1.44, and 2.26 (p = 0.005). These data lend support to the labeling by the International Agency for Research on Cancer of silica as a human carcinogen. There are approximately 2 million US workers exposed to silica; 100,000 are exposed to more than 0.1 mg/m(3).
 ...
PMID:Lung cancer among industrial sand workers exposed to crystalline silica. 1159 92

A 76-year-old male died of lung cancer. At first, he was diagnosed as a silicosis, because he had worked for 30 years as a caster in shipyard and large opacities detected by chest x-ray and CT scanning. After the operation of lung cancer, numerous asbestos bodies were observed in the operated lung tissues. The detailed occupational inquiry revealed his asbestos use as a caster in shipyard. Early stage of asbestosis was suspected by chest CT scanning, but not definitely diagnosed in premortal examinations. Asbestosis, pleural plaques, silicosis and large cell carcinoma of the lung were histopathologically confirmed at the autopsy. A patient with asbestos-induced lung cancer complicated by silicosis was rarely published in the literature.
 ...
PMID:A patient with asbestos-induced lung cancer complicated by silicosis. 1134 51

Progressive massive fibrosis (PMF) of the lung is caused by coalescence of fibrotic nodules. The center of the PMF often displays necrotic areas. If the necrosis gets in contact to the bronchial system cavitation may occur. We report on a 68 year old patient suffering from severe silicosis of the lung and metastatic spread of a histologically proven lung cancer into the brain. The patient who was administered to the hospital under the intention of cerebral radiotherapy showed a colliquative PMF in the right upper lobe with cavitation and expectoration of large amounts of black-stained sputum (melanoptysis).
 ...
PMID:["Phtisis atra"--a now seldom disease picture as a special disease course of silicosis]. 1140 74

In 1997, the International Agency for Research on Cancer (IARC) upgraded its evaluation of crystalline silica to a Group 1 human carcinogen. Criticism against such decision is based on the lack of consistency in experimental results across animal species, violation of an important principle for causality, such as the replication of findings under different circumstances of exposure, and the lack of a clear dose-response curve. The most recent epidemiological literature on the silica-silicosis-lung cancer link replicates the inconsistent findings that have been characterising 50 years of scientific debate in the occupational arena. Exposure circumstances capable of modifying the silica-lung cancer association include chronic bronchitis, composition of the dust mixing, particularly concerning co-occurrence of other known or probable lung carcinogens, total respirable dust, concentration of silica in respirable dust, type of crystalline silica and particle surface characteristics. The hypothesis of a silicosis-mediated pathway points toward an unspecific mechanism shared with other fibrotic conditions, for which silica might be just one of the triggers. In envisaging a multivariate multistep model of lung cancer among silica-exposed workers, silica might be considered as a "passive components of the sufficient cause", i.e., one of the associated risk factors, concurrent or subsequent to the "active component(s) of the sufficient cause" (including, for instance, smoking, asbestos, radon-daughters, arsenic, hexavalent chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and diesel exhausts among the external risk factors; and DNA repair enzymes polymorphism and spontaneous inactivation of tumour suppressor genes among the internal risk factors), which adds up in modulating the tumoral development in not easily predictable directions. If silica acts as a human lung carcinogen depending on certain occupational exposure circumstances, perhaps those circumstances and not silica itself should be classified for their human carcinogenicity potential.
 ...
PMID:Multifactorial aetiology of lung cancer among silica-exposed workers. 1160 27

Collaborative studies of Chinese workers, using over four decades of dust monitoring data, are being conducted by the National Institute for Occupational Safety and Health (NIOSH) and Tongji Medical University in China. The goal of these projects is to establish exposure-response relationships for the development of diseases such as silicosis or lung cancer in cohorts of pottery and mine workers. It is necessary to convert Chinese dust measurements to respirable silica measurements in order to make results from the Chinese data comparable to other results in the literature. This article describes the development of conversion factors and estimates of historical respirable crystalline silica exposure for Chinese workers. Ambient total dust concentrations (n>17000) and crystalline silica concentrations (n=347) in bulk dust were first gathered from historical industrial hygiene records. Analysis of the silica content in historical bulk samples revealed no trend from 1950 up to the present. During 1988-1989, side-by-side airborne dust samples (n=143 pairs) were collected using nylon cyclones and traditional Chinese samplers in 20 metal mines and nine pottery factories in China. These data were used to establish conversion factors between respirable crystalline silica concentrations and Chinese total dust concentrations. Based on the analysis of the available evidence, conversion factors derived from the 1988-1989 sampling campaign are assumed to apply to other time periods in this paper. The conversion factors were estimated to be 0.0143 for iron/copper, 0.0355 for pottery factories, 0.0429 for tin mines, and 0.0861 for tungsten mines. Conversion factors for individual facilities within each industry were also calculated. Analysis of variance revealed that mean conversion factors are significantly different among facilities within the iron/copper industry and within the pottery industry. The relative merits of using facility-specific conversion factors, industry-wide conversion factors, or a weighted average of the two are discussed. The exposure matrix of the historical Chinese total dust concentrations was multiplied by these conversion factors to obtain an exposure matrix of historical respirable crystalline silica concentrations.
 ...
PMID:Estimating historical respirable crystalline silica exposures for Chinese pottery workers and iron/copper, tin, and tungsten miners. 1171 59

In spite of the extensive use of cytogenetic analysis of human peripheral blood lymphocytes in the biomonitoring of exposure to various mutagens and carcinogens, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort. Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman's correlation coefficient R=0.22, P<0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman's correlation coefficient R=0.16, P<0.02). Smoking and silicosis were not associated with results of cytogenetic analyses. The Cox regression models, which accounted for the age at time of first cytogenetic assay, radon exposure, and smoking showed strong and statistically significant associations between cancer incidence and frequency of chromatid breaks and frequency of aberrant cells, respectively. A 1% increase in the frequency of aberrant cells was paralleled by a 62% increase in risk of cancer (P<0.000). An increase in frequency of chromatid breaks by 1 per 100 cells was followed by a 99% increase in risk of cancer (P<0.000). We obtained similar results when we analyzed the incidence of lung cancer and the incidence other than lung cancer separately. Contrary to frequency of chromatid breaks and frequency of aberrant cells, the frequency of chromatid exchanges, and chromosome-type aberrations were not predictive of cancer.
 ...
PMID:Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations. 1181 55


<< Previous 1 2 3 4 5 6 7 8 9 10