Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey

Our plain-English summary of Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey, by A.U. Dogan, Y.I. Baris, M. Dogan, et al (Cancer Research, 2006).

The study

• Authors: A.U. Dogan, Y.I. Baris, M. Dogan, S. Emri, I. Steele, A.G. Elmishad, M. Carbone
• Journal: Cancer Research
• Published: 2006;66(10):5063-8
• Cited by: 112 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This study asked why malignant mesothelioma is very common in three Cappadocian villages in Turkey (Tuzkoy, Karain and 'Old' Sarihidir) but not in nearby Karlik. The exposure studied was erionite, a fibrous zeolite mineral, not asbestos. The authors analysed erionite from all four villages and a control sample from Rome, Oregon. Of 70 samples, 17 gave acceptable analyses. Within each village, they found no differences in the composition or presence of erionite between houses with high, low or no mesothelioma, and all houses tested contained erionite. They also drew family trees. In one family, 17 of 30 members died of mesothelioma. Five of them had married into the family, and these also came from mesothelioma families. Among family members aged 26 to 45, none of 24 raised outside 'Old' Sarihidir had developed mesothelioma, compared with 3 of 29 raised in the village (estimated odds ratio 6.47). The authors concluded that the epidemic is caused by erionite exposure in genetically predisposed people. They noted it may take 20 to 40 more years to know whether relatives raised outside the village develop the disease.

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: Mineralogical (chemical and crystal-structure) analysis of erionite samples combined with family pedigree (family tree) analysis
• Who was studied: Erionite rock samples (70 collected, 17 usable) from the mesothelioma villages of Tuzkoy, Karain and 'Old' Sarihidir and the non-mesothelioma village of Karlik in Cappadocia, Turkey, plus a control erionite from Rome, Oregon. Families in the three mesothelioma villages: 18 pedigrees from 'Old' Sarihidir, 3 from Karain and 3 from Tuzkoy.
• Exposure: Environmental exposure to erionite, a fibrous zeolite mineral (not asbestos), in village houses
• Main results:
  • Only 17 of the 70 erionite samples gave acceptable balance errors. The rest contained other minerals and were not analysed further.
  • Within the same village, erionite composition and presence did not differ between houses with high mesothelioma incidence and houses with low or no incidence. All houses tested contained erionite.
  • Tuzkoy had predominantly erionite-Na. Karain, 'Old' Sarihidir, Karlik (non-mesothelioma village) and the Oregon control had predominantly erionite-K.
  • Iron oxide (Fe2O3) content was higher in erionite from the mesothelioma villages and from Oregon than from Karlik. The authors said it was unclear whether this relates to cancer-causing ability, because Oregon had the highest amount.
  • The crystal structure of a single grain from Tuzkoy identified it as erionite and showed it was not the similar mineral offretite.
  • In one family (family 1, from 'Old' Sarihidir), 17 of 30 members died of malignant mesothelioma, including 5 people who married into the family.
  • Those who married into family 1 and developed mesothelioma were themselves from mesothelioma families.
  • When members of a high-incidence family married into families with no history of mesothelioma, descendants developed mesothelioma.
  • Of the 18 'Old' Sarihidir pedigrees, 10 families had two or more mesothelioma cases, 4 had one case and 4 had none.
  • None of 24 descendants of family 1, aged 26 to 45, who were born and raised outside 'Old' Sarihidir after it was abandoned had developed mesothelioma.
  • In the same age group, 3 of 29 family 1 members born and raised in 'Old' Sarihidir developed mesothelioma. The estimated odds ratio between the two groups was 6.47; no confidence interval was reported.
  • All 10 Cappadocian mesothelioma samples tested negative for the virus SV40. In comparison, 2 of 5 U.S. mesothelioma samples tested positive.
• The authors' conclusion: The authors concluded that the mesothelioma epidemic in the three Cappadocian villages is caused by the interaction of erionite exposure with genetic predisposition.
• Limitations the authors state:
  • Family members raised outside 'Old' Sarihidir have not been followed long enough. It may take 20 to 40 more years to know whether they develop mesothelioma at all.
  • The analytical methods used differ from those of earlier studies and might explain some differences in composition, though the authors judged this unlikely.
  • It is unclear whether the differences in iron content found are related to the mineral's ability to cause cancer.
  • Whether erionite from the different villages and from the United States has similar biological effects has not yet been tested in cell culture or animals.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, Karain, erionite, Zeolite, Carcinogenic.

Related studies

• Lung diseases due to environmental exposures to erionite and asbestos in Turkey — S. Emri, A. Demir, et al. (2002)
• Malignant pleural mesothelioma in Turkey, 2000-2002 — S. Emri, A.U. Demir (2004)
• Erionite bodies and fibres in bronchoalveolar lavage fluid (BALF) of residents from Tuzköy, Cappadocia, Turkey — P. Dumortier, L. Coplü, et al. (2001)
• Erionite exposure in North Dakota and Turkish villages with mesothelioma — M. Carbone, Y.I. Baris, et al. (2011)
• Endemic malignant mesothelioma: exposure to erionite is more important than genetic factors — M. Metintas, G. Hillerdal, et al. (2010)
• Erionite series minerals: mineralogical and carcinogenic properties — A.U. Dogan, M. Dogan, et al. (2008)

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