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Update from Mesothelioma Information
In our ongoing extracts from the Program Report of the International Mesothelioma Program the IMP reviews how their . . .
Study of Asbestos Fibers May Hold One Key to Mesothelioma Susceptibility
The dictionary defines epidemiology as "1: a branch of medical science that deals with the incidence, distribution, and control of disease in a population; 2: the sum of the factors controlling the presence or absence of a disease or pathogen".
John Godleski, MD, head of pulmonary pathology at Brigham and Women's Hospital and a member of the IMP research team, is applying that definition in his research focusing on the types of asbestos associated with the development of mesothelioma. "Although other causal possibilities have been raised, the only consistent association with the development of mesothelioma is asbestos," said Godleski. "Our project studies concentrations of fiber types in patients with mesothelioma in the hope of better defining fiber types of asbestos or other fibers that may contribute to the development of mesothelioma."
There are two main sources of asbestos fibers – commercial or industrial products, such as the asbestos used in construction, and naturally occurring asbestiform fibers found in the environment. Asbestiform fibers are asbestos-like materials with a chemical composition just slightly different from asbestos. "For example," said Godleski, "there is a high incidence of mesothelioma in a particular village in Turkey, which is built on rock formations that are composed of erionite, an asbestos-like fiber. In the past, vermiculite associated with a particular source in Libby, Montana, was contaminated with tremolite, another asbestiform fiber. And tremolite fibers also have been found in talc."
In addition to analyzing fiber types, Godleski's lab also studies the concentration and distribution of asbestos fibers in patients with mesothelioma. The concentration of fibers in tissue samples from the lungs of mesothelioma patients – the asbestos body count, or number of coated asbestos fibers on the lung – is tested by light microscopy techniques, which readily reveal the iron-coated asbestos fibers. Electron microscopy is used to identify the specific type of fiber present, "which can tell us something about the source, whether commercial or environmental," said Godleski.
The distribution of fibers within the thoracic cavity – in the lung, the parietal and visceral pleura, and in the thoracic lymph nodes, as well as in the mesothelioma tumor itself – is important information for researchers. "Cells of the lung respond to asbestos fibers by forming an iron coat around them," said Godleski. "Fibers found in other areas of the body usually do not have this iron coat. So we're looking for answers to questions such as whether these non-coated fibers have escaped from the lung, whether there is a transport mechanism in the lung by which fibers are distributed elsewhere, and so on."
These studies are important because the incidence of mesothelioma appears to be increasing, particularly among women. "If you think about it," said Godleski, "one would expect that rates should be decreasing, not increasing." Knowledge of the dangers of asbestos exposure came to light in the 1960s, and was well known by the 1970s in the medical community in industry and even among workers. Because of the long latency period for development of mesothelioma after exposure – which is 20-30 years – many patients now are in their fifties who could have entered the work force at age 20 and were exposed perhaps 30 years ago. "One way of thinking about this is that the numbers are rising now, but there'll be a plateau, then a decrease," said Godleski. "The prediction is that we should be well into the plateau already yet we do not appear to be. The U.S. has not banned the use of asbestos, and, in fact, there still remains a substantial amount of asbestos in the environment to which one can be exposed."
Mesothelioma traditionally has been an occupationally related disease affecting men in the building trades, and in shipbuilding and manufacturing. "Generally" said Godleski, "women haven't been in those occupations or present at those work sites. For the most part, the development of the disease in women was thought of as secondary exposure, for example, by a wife washing her husband's work clothes. But the question remains – are women exposed in workplaces where we don't appreciate that there might be the possibility of exposure? Are there other risk factors for women that we have not discovered?"
Godleski's research hopes to find answers to these and other questions. He and his colleagues are hoping to identify potentially new sources of asbestos fibers that have not yet been recognized as important. "The biggest potential finding we could make," said Godleski, "is to recognize new forms of asbestos or asbestiform fibers, or other fiber types that contribute to the development of the disease in individuals and populations."
A second research goal is to better understand "the pathways through which fibers translocate from the deposition site in the small airways of the lungs to the pleural space for eventual development of the disease," he said. There are a number of possible transit routes for asbestos fibers within the lungs. Peritoneal mesothelioma (a cancer of the cells lining the abdominal cavity) is less common, but also related to asbestos exposure. How the fibers translocate to this site also is of interest to mesothelioma researchers. Possible pathways may be through the lymphatic system, through ingestion and through the intestinal tract into the peritoneal space, or through migration from the lungs into the abdomen. "We can gain insight into intrapulmonary translocation as well as systemic distributions by learning more about the fibers themselves and where they are in the lung," said Godleski.
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