The Epidemiology and Origins of Mesothelioma
It has been estimated that mesothelioma has an annual incidence rate of around 2700 cases in the United States. It appears that the incidence of mesothelioma in the US reached its peak around the year 2000, and has stabilized, probably due to control in exposure to asbestos.
The incidence of mesothelioma has increased in several places worldwide, especially in Great Britain, where deaths resulting from mesothelioma are expected to reach a peak of 2450 around the year 2015. Beyond that point, the incidence rates of mesothelioma are expected to come down in the UK as well as other developed nations because regulations have been enacted to reduce exposure to asbestos at the workplace and in the general environment. In comparison, the incidence rate of mesothelioma is expected to increase in Third World countries due to poor regulation of asbestos mining and the increased household and industrial use of asbestos.
Exposure to asbestos
Asbestos is the commercial name given to a specific group of hydrated magnesium silicate fibrous minerals. Asbestos can be classified as serpentine and amphibole. Approximately 90% of the asbestos used in the US is Canadian chrysotile, a serpentine type of asbestos.
Asbestos was an important mineral for industry because of its heat and combustion resistant qualities. It is still widely used in ceiling and pool tiles, cement, shipbuilding and automobile brake linings.
Over the past 50 years, as many as 8 million American have experienced exposure to asbestos. Based on clinical evidence that showed that exposure to asbestos may adversely affect the health of American workers, an exposure limit of 5 fibers per cubic milliliter of air was established as the standard by the Occupational Safety and Health Administration in 1970. This limit has been further reduced to 0.2 fibers for every cubic milliliter of air. This applies to fibers that are longer than 5 micrometers. Workers who are likely to experience higher levels of exposure are mandated to wear protective clothing and respirators.
Asbestos workers face considerable risk for the onset of both non-malignant and malignant forms of pulmonary disease.
The website uptodate.com reports that experts estimate the lifetime risk of developing mesothelioma in case of asbestos workers is as much as 10%. A long latency of three to four decades passes from the time of exposure to asbestos and the onset of mesothelioma.
There exists a dose-response relationship between exposure to asbestos and mesothelioma. This was demonstrated in a cohort study involving 4600 individuals who were residents of an Australian city (that produced crocidolite asbestos), but were not directly involved in the mining or milling of asbestos. It was noticed that incidence of mesothelioma increased substantially with increased environmental exposure, depending upon the neighborhood and period of residence. In a cohort study involving textile workers with high levels of asbestos exposure, it was noticed that the risk of pleural mesothelioma had increased and was relative to the latency period.
When combined with smoking, exposure to asbestos can increase the risk of lung cancer development by almost 60 times as compared to a similar cohort involving non-smoking, non-asbestos-exposed study subjects.
It is believed that asbestos workers also face an increased risk of developing non-mesothelioma gastrointestinal malignancies.
An increased risk of developing mesothelioma may also be due to environmental, nonoccupational asbestos exposure. In some rural areas of Bulgaria, Turkey, and Greece, the soil has high levels of tremolite asbestos. In these regions, several different cases of mesothelioma were linked with long-term nonoccupational exposure to asbestos. This was further verified in a California based study which demonstrated a link between an increased incidence of mesothelioma and proximity to naturally occurring asbestos deposits.
Asbestos exposure has been held responsible for a significant number of peritoneal mesothelioma cases, although this association may not be as strong as that of pleural mesothelioma.
Ionizing radiation to supradiaphragmatic tissue can be a potential risk factor for the subsequent onset of pleural mesothelioma. In this case the mesothelioma would be the second cancer; the radiation used to treat the first cancer caused the mesothelioma. There is typically a long latency period between the time when radiation treatment is administered and the diagnosis of the second malignancy.
According to the website uptodate.com, a study involving over 75,000 Non-Hodgkin’s Lymphoma patients from the Surveillance, Epidemiology and End Results (SEER) database, an increased risk of mesothelioma was noticed in cases when radiation therapy was administered. Individuals who were below 25 years of age at the time of initial diagnosis faced the highest risk.
In a population-based study involving more than 40,000 men who had received treatment for testicular cancer between 1943 and 2001 and were followed on a long term basis, it was noticed that there were 10 additional cases of pleural mesothelioma (relative risk 4) in cases when the patients had received only radiation therapy.
The data pertaining to breast cancer patients is conflicting. In an analysis involving 22,140 patients who received treatment in 11 National Surgical Adjuvant Breast Project (NSABP) trials, 3 mesothelioma cases were identified, all occurring among women who had received radiation treatment to the ipsilateral thorax. In comparison, a study of the SEER database cohort of more than 250,000 was not able to establish a link between radiation and the subsequent onset of pleural mesothelioma.
Prophylactic mediastinal irradiation is not used anymore for treating testicular germ cell tumors and its use has been significantly reduced among patients with HL and NHL. However, there are still a significant number of cancer survivors who continue to face the risk of late onset of mesothelioma.
Carbon nanotubes have similar physical characteristics and dimensions as asbestos fibers. Studies in animal models have demonstrated that these particles can bring about mesothelioma-like changes in tissue.
Use of carbon nanotubes is expected to increase significantly and many have raised the concern that epidemiologic vigilance is necessary to ensure that these do not become a new etiologic source of malignant mesothelioma.
A polyoma virus, the Simian virus-40 (SV-40) has shown oncogenic potential among humans. It is believed that the actions of this virus result from the inactivation of tumor suppressor genes belonging to the retinoblastoma family by a peptide referred to as the SV-40 large T-antigen. A number of studies have detected the presence of SV-40 nucleic acids in some mesothelioma cases. For instance, a report that analyzed 35 archival mesothelioma specimens, found SV-40-like sequences in around 86% of cases. However, there have been questions regarding the possibility that technical reasons (including laboratory contamination) can produce false-positive outcomes indicative of SV-40 infection.
Although possible, it has not been confirmed that viral interferences with tumor suppressor genes can play a significant role in promoting the development of malignant mesothelioma. In the event of this hypothesis being validated, newer vaccination strategies to prevent mesothelioma, or novel molecular methods to achieve early diagnosis may become a possibility.
Other etiologic factors
In rare cases, the onset of malignant pleural mesothelioma has also been linked with intrapleural thorium dioxide (Thorotrast), and inhalation of other types of fibrous silicates, for instance erionite. In epidemiological studies conducted in a specific region in central Anatolia (Turkey) where the incidence of pleural mesothelioma was abnormally high (22 cases for every 10,000 individuals over 25 years of age), the routine household use of a locally available silicate – zeolite, was identified as the potential causative factor.
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