Causes & Risk Factors of Mesothelioma

Since doctors first found tumors on the lining of a patient’s lung in 1890, researchers have entertained several theories about what causes pleural mesothelioma. It wasn’t until 1960, however, that a scientist named J.C. Wagner clearly attributed this cancer to asbestos exposure.

Wagner’s team identified 33 cases of the disease over a four-year period; 32 had a history of asbestos exposure. (All but four of the exposed patients worked in or lived near the town’s asbestos mines.) Since then, multiple studies have confirmed the relationship between asbestos and pleural mesothelioma.

The asbestos industry continues to argue that certain types of asbestos do not cause pleural mesothelioma. However, researchers maintain that all types of asbestos — including amphibole and chrysotile — can cause cancer.

Types of Asbestos Exposure that Cause Pleural Mesothelioma

Patients with pleural mesothelioma have reported several sources of asbestos exposure. Many of the sources fall into one of the following categories:

Sources of exposure Examples
Asbestos mines and processing plants Jeffrey Asbestos Mine; WR Grace Vermiculite Plant
Industrial worksites (non-asbestos industry) National Gypsum drywall factory; construction sites
Shipyards Todd Shipyards; Hunters Point Naval Shipyard
Military facilities USS Alabama; Fort Bragg; Brooklyn Navy Yard
Areas with active asbestos mines or naturally occurring deposits Libby, Montana; Coalinga, California

By far, the majority of exposures occurred at industrial job sites. Until the 1980s, asbestos heavily contaminated worksites like refineries and power plants. Many workers sustained long-term, high-dose exposure over the course of their careers. This type of exposure is the most likely to lead to disease.

Patients have also been exposed outside of the workplace — although on a less frequent basis. These exposures may have come from asbestos-contaminated consumer products, like loose-fill insulation, or asbestos that came home on the clothing or skin of an asbestos worker, which is known as secondhand exposure. Secondhand asbestos exposure attests to the fact that low-level asbestos exposure over a long period of time can cause pleural mesothelioma. In a handful of cases, patients encountered the fibers in the natural environment.

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How Does Asbestos Cause Pleural Mesothelioma?

Pleural mesothelioma develops after a person inhales asbestos. As the long, thin fibers pass through the respiratory pathway, they can get trapped in the lining of the lung — known as the pleura.

Once trapped, the fibers can trigger a carcinogenic process that takes between 10 and 50 years to cause cancer. Researchers aren't completely sure how this process works, but they have several theories:

Theory Description
Cellular inflammation "Observations support a scenario [where] mesothelial cells undergo a series of chronic injury, inflammation and proliferation," according to a 2013 study in the American Journal of Pathology.
Genetic mutations Asbestos may cause genetic changes that can lead to cancer. These changes may include "mutations in genetic susceptibility or cell cycle genes," according to the American Journal of Pathology article.
Free radical-induced damage Inside the body, asbestos may trigger free radical production. Some of these free radicals, known as reactive oxygen species, may intensify the toxicity of asbestos fibers, while triggering additional damage to mesothelial cells.
Growth pattern overrides Asbestos may trigger the production of oncoproteins. These substances can override cell programming that controls growth, in turn allowing cells to divide too quickly and become cancerous.

Certain factors may make people more likely to develop pleural mesothelioma after sustaining asbestos exposure. Smoking weakens the lungs and may make them more susceptible to developing asbestos-related lung cancer, but smoking does not increase the risk of mesothelioma in anyone with a history of asbestos exposure. Genetics may serve as a risk factor; research is underway to understand the genes and related biological processes that contribute to pleural mesothelioma. This genetic factor may help explain why some people develop pleural mesothelioma after exposure, while others who are exposed do not.

The level and duration of asbestos exposure can also affect someone's risk of developing this pleural disease. Even low-level exposure to asbestos can cause pleural mesothelioma. Renowned asbestos researcher Gunnar Hillerdal reported in 1999: "There is no proof of a threshold value — that is, a minimal lower limit below which asbestos fibers cannot cause the tumor — and thus it is plausible that even such low exposure can cause mesothelioma (even if the risk is extremely low)."

A 1998 study by Iwatsubo et al. found an excess of pleural mesothelioma cases among the lowest exposure group participating in the study. Multiple studies demonstrate a dose-response relationship between asbestos exposure and pleural mesothelioma, meaning that as asbestos exposure increases so does the inhalation of asbestos fibers into the lungs, which in turn increases the risk of developing pleural mesothelioma.

Can Pleural Mesothelioma Be Unrelated to Asbestos?

On rare occasions, patients without a history of asbestos exposure have developed pleural mesothelioma. Many non-asbestos pleural mesothelioma cases come from exposure to minerals that closely resemble asbestos in structure, known as asbestiform minerals. Winchite and richterite are two examples of asbestiform minerals that have caused pleural mesothelioma. Some non-asbestiform minerals are associated with mesothelioma, including the zeolite mineral called erionite and the iron formation called taconite.

Research shows that at least 80 percent of all mesothelioma cases are caused by asbestos exposure. Other non-mineral causes may include radiation, chemicals, metals and inflammation. Studies on other causes show mixed results, but radiation seems to be a definitive cause in a handful of mesothelioma cases. Some studies have investigated whether Simian Virus 40 plays a causative role, but the results are inconclusive.

Pleural mesothelioma rarely develops without a specific cause. However, pediatricians have reported a very small number of spontaneous cases in children.

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