Etiology of Pericardial Mesothelioma

Mesothelioma is a cancer that arises from mesothelial cells, which are the cells that line various cavities in the body. Mesothelial cells exist in the space around the lungs, called the pleura; the space around the intestines, called the peritoneum; and the space around the heart, called the pericardium. These lining cells are also found around the testes. Their primary function is to provide a slippery but firm, protective surface so that organs can slide across more external portions of the body. Mesothelial cells also have many other biological functions.1 When these cells transform into cancer, however, it creates a chain of events that leads to a serious medical condition known as malignant mesothelioma. Since mesothelial cells occur in various places in the body, mesothelioma can originate in various anatomical locations.

Causes of mesothelioma Asbestos

Asbestos is a crystalline, fibrous substance that is the smallest naturally occurring fiber known to man. It forms and has a number of remarkable physical properties. Asbestos is both incredibly durable and flexible such that it can be molded to fit almost any area while resisting heat, electricity, and chemical corrosion. Because of these versatile properties, asbestos was aggressively mined throughout the late 19th and most of the 20th centuries. Sites with the highest asbestos mining production include the United States, Central, Western, and Mediterranean Europe, and the former Soviet Union.

Asbestos is found in a cornucopia of products. The transportation industry used asbestos in everything from airplanes to automobiles to ships. The defense industry and related contractors also saw many applications for asbestos including missiles and torpedoes. Brake linings and pads were a common place to find asbestos given the substance’s resiliency and durability under extremes of temperature. The fiber’s ability to resist changes in temperature also earned it a place in building materials, mostly insulation. Consumption rose sharply just after World War Two and hit its global peak in the 1970s.

There are two main types of asbestos fiber, chrysotile and amphibole, though amphibole fibers occur in several subtypes including amosite, crocidolite, and tremolite. While all types of asbestos are associated with increased risk of lung disease and cancer, the rate of mesothelioma is much greater after amphibole exposure than chrysotile.4 In fact, tremolite exposure appears to pose the greatest cancer risk among asbestos fiber types and the contamination of chrysotile with tremolite fibers may explain reports of cancers from chrysotile.5 It is felt that amphibole exposure greatly increases the risk of mesothelioma because of its shape and the way in which the body processes it after exposure.

Amphibole fibers are persistent in the lung and resist removal by macrophages and other immune system cells. The dangers of asbestos, in particular its role in lung disease and cancer, was not fully appreciated until the use of the material dominated construction projects globally. Anyone working with asbestos was potentially at risk, though certain professions posed greater risk. The mining of asbestos obviously poses a great risk since the particles are constantly being sent into the air during extraction from the ground.

At one time the substance was extruded from a hose to fill in areas that require nsulation from heat or cold. However, these large exposures were far greater than the asbestos xposure needed to cause serious disease. Simply handling asbestos could be enough to pose a health risk. In fact, because asbestos fibers are so small and can attach to virtually any substance, asbestos workers carried the fibers home to their spouses and, in laundering the asbestos-laden clothing, also acquired related lung diseases.

It is fairly clear from epidemiological studies that the link between asbestos exposure and malignant mesothelioma is both dose-dependent and dependent on the duration of exposure. This means that the risk of developing this cancer increases as the amount of time spent in the aerosolized (airborne) asbestos-containing environment increases. Of note, undisturbed asbestos is not harmful nor is it linked to lung disease. The number of malignant pleural mesothelioma case increased exponentially as asbestos use became more prominent. The term “increased exponentially“ means that small increases in the amount of exposure to asbestos exponentially increase the risk of developing the disease (cubic power function).

Mesothelioma was considered an extremely rare cause of cancer before asbestos became widely used in industrial, commercial, automotive, and residential venues. As asbestos use increased over the past 150 years, the rates of asbestosis and mesothelioma increased sharply and in parallel. Since Lynch and Smith first documented a patient’s death from asbestos-related lung cancer in 1935, the epidemiological evidence linking asbestos exposure and mesothelioma has been substantial. It has been estimated that 80% of all people with mesothelioma that have been exposed to asbestos either directly or indirectly.

Depending on the study, however, the estimates range between 16 and 90%.11 Part of this variation can be explained by differences in exposure time, amount of asbestos exposure, and the type of asbestos fiber studied. In regards to the last issue, studies involving individuals solely exposed to chrysotile fibers show numbers on the low end of that range compared to those exposed to amphibole asbestos fibers. While this variability caused some to doubt a causal link throughout much of the 1900s, the link between asbestos exposure and mesothelioma is now considered irrefutable.

1. Radiation

While asbestos exposure is the leading cause of mesothelioma, other causes exist as well. Radiation exposure has been linked to the cancer in people that have never had direct or indirect exposure to asbestos. For example, mesothelioma can occur after radiation treatment for cancer and radiation exposure in the environment. Patients receiving intravenous thorotrast, a radioactive solution that was used until the 1950s in medical radiological studies, also developed mesothelioma in numbers higher than others not exposed to asbestos. While the causal link between radiation exposure and mesothelioma is generally accepted, radiation appears more likely to cause forms of lung cancer other than mesothelioma.

2. Simian virus 40

Research is emerging that identifies a particular virus called Simian virus 40 in the development of malignant mesothelioma. Simian virus 40 is known to mostly affect people with compromised immune systems such as those with HIV/AIDS. The virus appears to cause particular tumors in humans including brain and bone tumors, lymphomas, and malignant mesothelioma15 It is estimated that Simian virus 40 may play a causative role in as many as half of all cases of malignant mesothelioma, however this link is still controversial.

3. Genetics

It is possible that mesothelioma is more likely in some families than in others. Genetic studies have

linked certain gene variants to increased rates of mesothelioma. For example, there are families in

Turkey that pass mesothelioma directly through their family in an autosomal dominant fashion The death rate from mesothelioma in this Turkish community is nearly 50%. It is true that this particular community has been exposed to very high levels of a compound known as erionite. While erionite is not asbestos, it does tend to cause mesothelioma. However this entire Turkish community is exposed to roughly the same levels of erionite yet mesothelioma exists only within some families and not others.

This suggests that erionite exposure plus a certain genetic makeup is responsible for mesothelioma among these people. There is separate evidence that a genetic susceptibility exists for people to develop mesothelioma after asbestos exposure. In a group of people that have had roughly equal exposures to asbestos, those individuals that carried certain forms of two particular genes were seven times more likely to develop mesothelioma. In essence, while asbestos exposure is still a primary causative factor, genetic background may at least partially determine who gets mesothelioma from asbestos and who does not.

4. Cigarette smoke

It is well-known that lung cancer is heavily influenced by smoking tobacco cigarettes. However the primary lung cancers that arise from cigarette use are small cell and non-small cell lung cancers. These are separate entities from mesothelioma because they arise from different cell types. For example, nonsmall cell lung cancers can be classified in adenocarcinoma, large cell carcinoma, and squamous cell carcinoma; mesothelial cells are not a part of these major cancer types. Asbestos exposure also increases the risk of small cell and non-small cell lung cancers. In fact, there is a synergistic effect of cigarette smoking and lung cancer which increases the risk dramatically (i.e. smoking and asbestos exposure increase lung cancer risk far beyond the risk of either insult, even individually). However, smoking does not play a role in the development of mesothelioma.