Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 10; pp. 5063 - 5068
• Main Authors: DOGAN, A. Umran, BARIS, Y. Izzettin, DOGAN, Meral, EMRI, Salih, STEELE, Ian, ELMISHAD, Amira G, CARBONE, Michele
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-05-2006
• Subjects: Adult; Antineoplastic agents; Biological and medical sciences; Cocarcinogenesis; Disease Outbreaks; Environmental Exposure; Female; Genetic Predisposition to Disease; Humans; Male; Medical sciences; Mesothelioma - epidemiology; Mesothelioma - etiology; Mesothelioma - genetics; Middle Aged; Models, Molecular; Pedigree; Pharmacology. Drug treatments; Tumors; Turkey - epidemiology; Zeolites - chemistry; Zeolites - poisoning; Asia; Turkey; Epidemic; Nutrition; Diet; Predisposition; Tumor; Genetics; Mesothelioma; Dietary fiber; Carcinogenesis; Public health; Feeding
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-05-4642

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.