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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.
Prospective study of mesothelioma mortality in Turkish villages with exposure to fibrous zeolite.Mesothelioma incidence is high in certain villages on the Anatolian plateau in Turkey, where environmental exposure includes erionite, a form of zeolite fibers, from the local volcanic tuff. Previous studies of this exposure were cross-sectional or with a follow-up period of only a few years. A prospective study of residents of two exposed and one nearby control village was initiated in 1979 and continued through December 31, 2003. A total of 891 men and women, aged 20 years or older, were included, 230 of them residing in the village without known exposure to erionite. Mortality data were obtained from hospital records and death certificates. During the 23-year follow-up, 372 deaths occurred; 119 of these were from mesothelioma, which was the cause of 44.5% of all deaths in the exposed villages. Seventeen patients had peritoneal mesothelioma; the rest had pleural mesothelioma. Only two cases of mesothelioma, one of each type, occurred in the control village-both in women born elsewhere. When standardized to the world population, the pleural mesothelioma incidence was approximately 700 and 200 cases per 100,000 people annually in the two exposed villages and about 10 cases per 100,000 people in the control village. When we used Danish data for comparison, the standardized pleural mesothelioma mortality rate was 485 (95% confidence interval = 395 to 590). Our results emphasize the severity of the mesothelioma endemic in erionite-exposed areas of Turkey and call for intensified prevention of mesothelioma by limiting environmental exposures to these fibers.