The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad

Our plain-English summary of The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad, by S.A. Emri (Annals of Translational Medicine, 2017).

The study

• Author: S.A. Emri
• Journal: Annals of Translational Medicine
• Published: 2017;5(11):239
• Type of article: Review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about 50% of all deaths (including neonatal deaths and traffic fatalities) have been caused by mesothelioma. No other epidemic in medical history has caused such a high incidence of death. This is even more unusual when considering that (I) epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a rare cancer. World-wide mesothelioma incidence varies between 1/106 in areas with no asbestos industry to about 10-30/106 in areas with asbestos industry. This article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr. Baris (my mentor), how we initially linked the epidemic to erionite exposure, and later (with Dr. Carbone) to the interaction between genetic predisposition and environmental exposure. Our team's work had an important positive impact on the lives of those living in Cappadocia and also in many genetically predisposed families living around the world. I will discuss how the work that started in three remote Cappadocian villages led to the award of a NCI P01 grant to support our studies. Our studies proved that genetics modulates mineral fiber carcinogenesis and led to the discovery that carriers of germline BAP1 mutations have a very high risk of developing mesothelioma and other malignancies. A new, very active field of research developed following our discoveries to elucidate the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to identify additional genes that when mutated increase the risk of mesothelioma and other environmentally related cancers. I am the only surviving member of this research team who saw all the phases of this research and I believe it is important to provide an accurate report, which hopefully will inspire others.

In plain English

This article is a narrative review and personal account by the author, a Turkish chest physician, of research on the mesothelioma epidemic in three Cappadocian villages: Karain, Tuzkoy and Sarihidir. It presents no new data. It recounts earlier studies by the author's team, collaborators and other groups. The author describes a 1975 visit in which the team X-rayed about 200 Karain residents over age 20 and diagnosed 12 with probable mesothelioma, all later confirmed by biopsy. Men and women were affected about equally, as were the pleura and the peritoneum. Cited studies found erionite, a fibrous mineral, in patients' lung tissue and in village air, and the epidemic was attributed to erionite in building stones and road gravel. The author recounts family-tree studies suggesting inherited susceptibility, the move of Tuzkoy villagers into 224 new homes, and air sampling that found no erionite in new Tuzkoy. The author also recounts the finding of germline BAP1 mutations in two US families. The gene behind the Cappadocian family cases has not been identified. The author concluded that this research led to BAP1, described as the first, and so far only, gene that modulates mineral fiber carcinogenesis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review and personal historical account of earlier research; no new data or methods
• Who was studied: Residents of the Cappadocian villages of Karain (about 800 people at the time, about 200 X-rayed in 1975), Tuzkoy (about 3,000 people) and Sarihidir in Turkey, plus US families with high mesothelioma incidence studied by collaborators
• Exposure: Environmental exposure to erionite, a fibrous mineral, present in the stones used to build village houses and the gravel used to pave roads; asbestos exposure in other central Anatolian villages is also described
• Main results:
  • In an earlier survey in Mihaliccik, Dr. Baris reviewed 3,880 chest X-rays. 10% of the patients had pleural plaques and six had mesothelioma.
  • In Karain in 1975, 12 patients were diagnosed with probable mesothelioma, all later confirmed by chest biopsy and histology
  • In Karain, mesothelioma occurred about 1:1 in men and women and about 1:1 in the pleura and the peritoneum
  • Karain mesothelioma patients were in their early 50s, almost 20 years younger than mesothelioma patients the team had found in other villages
  • The author states that over 50% of all deaths in these villages were caused by mesothelioma
  • Earlier studies cited by the author found erionite in the lung tissue of affected patients and in the air of the three villages
  • A cited HLA study found the HLA-B41 antigen in 19.4% of patients compared with 0.8% of healthy controls among Tuzkoy inhabitants
  • A cited study of the virus SV40 in Cappadocian mesothelioma gave negative results
  • Pedigrees built by the team showed that susceptibility to mesothelioma was passed on as an autosomal dominant trait
  • Tuzkoy villagers were moved to a new town; 224 new homes were completed by 2004
  • Air sampling found no erionite in the air of new Tuzkoy
  • Air sampling also found erionite concentrations in school buses on erionite-paved roads in North Dakota as high as in the old mesothelioma village
  • Germline BAP1 mutations were found in all affected members of two unrelated US families, and not in non-affected members
• The authors' conclusion: The author concluded that the team-based research that began in Cappadocia led to the identification of BAP1, described as the first, and so far only, gene that modulates mineral fiber carcinogenesis
• Limitations the authors state:
  • The gene responsible for the high mesothelioma incidence in some Cappadocian families has not been identified, because DNA specimens can no longer be sent from Turkey to the USA
  • The genetic linkage analyses used to search for the gene were underpowered

Topics

Medical terms in this study, explained in our Lexicon: Cappadocia, Mesothelioma, Karain, erionite, Environmental Exposure, Mineral Fiber, Carcinogenesis, Discovery.

Related studies

• Erionite bodies and fibres in bronchoalveolar lavage fluid (BALF) of residents from Tuzköy, Cappadocia, Turkey — P. Dumortier, L. Coplü, et al. (2001)
• The crystal structure of the killer fibre erionite from Tuzköy (Cappadocia, Turkey) — C. Giacobbe, A. Moliterni, et al. (2023)
• Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey — A.U. Dogan, Y.I. Baris, et al. (2006)
• Mortality among United Kingdom servicemen who served abroad in the 1950s and 1960s — S.C. Darby, C.R. Muirhead, et al. (1990)
• Canada's asbestos legacy at home and abroad — J.T. Brophy, M.M. Keith, et al. (2007)
• The European mesothelioma epidemic — J. Peto, A. Decarli, et al. (1999)

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