Mesothelioma not associated with asbestos exposure.

CONTEXT: Despite asbestos being identified as the single most important cause of malignant mesothelioma, the tumor is known to occur in only 10% to 20% of heavily exposed individuals. In addition, about 20% of the patients have no history of asbestos exposure even after detailed assessment. Therefore, there has been speculation for some time that asbestos alone may not be sufficient to cause mesothelioma and that other factors may be involved either as cocarcinogens or as independent mechanisms of cancer causation. OBJECTIVE: To give a brief review of nonasbestos fiber erionite and therapeutic radiation as 2 established examples of asbestos-independent mechanisms, of the potential emerging role of man-made fibers such as carbon nanotubes, and of polyoma virus SV40 (simian virus 40) as a potential example of the cocarcinogenic mode of involvement. DATA SOURCES: Relevant recent literature has been surveyed to portray and provide the evidence in favor of the examples. CONCLUSIONS: Erionite has emerged as the most important example of nonasbestos-mediated cause of mesothelioma in regions such as Turkey where exposure to this type of fiber is highly prevalent. Recently, the polyoma virus SV40 has been unexpectedly discovered as an effective cocarcinogen of asbestos in the causation of animal mesothelioma, though despite considerable research, its potential role in human mesothelioma remains unproven.

Endemic malignant mesothelioma: exposure to erionite is more important than genetic factors.

The village of Karain, Turkey, has the world's highest prevalence rate of malignant mesothelioma (MM). Environmental exposure to erionite is thought to cause the disease. However, it has also been suggested that the disease is mainly genetic. Residents in Karain village were traced from 1990 to 2006. Mineral samples were obtained from stones used in construction of their houses and any fibers present were identified. All women who had moved to the village as brides were traced and their cause of death determined. MM was the cause of death in 52 of 322 villagers, representing 50.5% of all deaths. Only 2 of 8 types of stones used in construction contained erionite, and these stones had been used almost exclusively in the mid-sections of the village, where MM was common. In houses not containing erionite, no cases of MM were observed. Sixty-four women came as brides to Karain from villages where erionite or asbestos is not found. Of the 16 women who have died, 11 (69%) died from MM. The extreme risk of MM in Karain is due to indoor exposure to erionite. The effect of genetic factors on mesothelioma development cannot be evaluated in this study, but is likely to be minor.

Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey.

Malignant mesothelioma in the western world is often associated with asbestos exposure. It is a relatively rare cancer that causes approximately 2,500 deaths yearly in the United States and 1,000 deaths yearly in the United Kingdom. In contrast, among people born in the Cappadocian (Turkey) villages of Tuzkoy, Karain, and "Old" Sarihidir, approximately 50% of deaths are caused by malignant mesothelioma. This epidemic has been attributed to erionite exposure, a type of fibrous zeolite mineral commonly found in this area of Turkey. In these three villages, malignant mesothelioma occurs in certain houses but not in others. The hypothesis was that a unique and more carcinogenic erionite was present in certain houses and caused malignant mesothelioma. We determined the X-ray diffraction pattern and the crystal structure of erionite from malignant mesothelioma villages and compared the results with the erionite samples from nearby non-malignant mesothelioma villages and from the United States. We found the same type of erionite in Cappadocian villages, with or without a malignant mesothelioma epidemic, in households with high or no incidence of malignant mesothelioma and in the United States. Pedigree studies of the three malignant mesothelioma villages showed that malignant mesothelioma was prevalent in certain families but not in others. When high-risk malignant mesothelioma family members married into families with no history of it, malignant mesothelioma appeared in the descendants. Genetically predisposed family members born and raised outside the malignant mesothelioma villages did not seem to develop malignant mesothelioma. In summary, pedigree and mineralogical studies indicate that the malignant mesothelioma epidemic is caused by erionite exposure in genetically predisposed individuals. This is the first time that genetics is shown to influence mineral fiber carcinogenesis.

Prognostic significance of Bax and Fas ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma.

Environmentally exposed erionite is a potent and unique inducer of malignant pleural mesothelioma (MPM) in Central Anatolia in Turkey. Previous studies have shown that erionite induced MPM has different biological behavior than asbestos induced MPM. Although impaired apoptosis has been implicated in tumor biology, the relationship between the type of environmental exposure and apoptosis has not yet been evaluated in MPM. The purpose of this study was to determine the expression of apoptosis regulating proteins and their prognostic significance in erionite and asbestos induced MPM. Thirty-five patients with MPM (16 erionite and 19 asbestos induced), and 17 patients with adenocarcinoma were comparatively evaluated. Expression of Bcl-2, Bax, Fas and Fas Ligand, were assessed by immunohistochemistry. Bcl-2 and Fas did not stain in almost all specimens. The staining extension of Bax was 13.75 +/- 19.27%, 5.89 +/- 14.51% and 7.38 +/- 14.53% for erionite and asbestos induced MPM and adenocarcinoma, respectively (p = 0.566). The staining extension of Fas Ligand was 26.87 +/- 31.87%, 46.10 +/- 37.30% and 26.47 +/- 23.23% for erionite and asbestos induced MPM, and adenocarcinoma, respectively (p = 0.123). Bax negative patients in erionite group had longer survival than Bax positive patients (18 months versus 14 months) (p = 0.06). Fas Ligand positive patients showed statistically better survival than Fas Ligand negative patients in all MPM group (15 months versus 12 months) (p = 0.05). Although all proteins expressed in similar extension in all samples, Bax staining displayed an inverse relation with survival in erionite group. This may implicate a difference in Bax functioning in erionite induced MPM. However, Fas Ligand may be functionally intact to reduce tumor survival.