The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad

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.

Keywords: Erionite, BAP1; environmental mesothelioma; gene and environment interaction.

Figure 1

Tuzkoy Nov 1997: “house of death” (left), Dr. Dogan, (right) Dr. Carbone and children we found playing inside the abandoned home.

Figure 2

Sarihidir, Health Center. Blood collection for ELISA studies. Standing, right, Dr. Emri.

Figure 3

Our “office” in the village of Sarihidir. From left, Drs. Carbone, Baris, a mesothelioma patients and her niece, and Dr. Emri.

Figure 4

Extracting DNA for SV40 virus PCR study at University of Hacettepe, 1997. From left, Drs. Emri, Carbone, Mutti, and Kocagoz.

Figure 5

Mission accomplished, 2007. Dr. Baris (left), and Dr. Carbone (right) in the background the new village of Tuzkoy.