A rock and a hard place

from Nature Reviews Cancer

Jenny Bangham

Malignant mesothelioma — cancer of the lining of the chest or abdomen — is associated with exposure to asbestos and tends to be rare. But in three Turkish villages — Tuzkoy, Karain, and 'Old' Sarihidir — the disease is responsible for an astonishing 50% of deaths, and Michele Carbone and colleagues now have new clues as to what causes this.

It has long been thought that this Turkish epidemic is caused by the local presence of the carcinogen erionite — a fibrous glassy mineral used to build houses in the region. But the pattern of malignant mesothelioma is puzzling. First, erionite is found both in nearby Turkish villages and in other areas of the world, such as the United States, where it is not associated with the disease. Second, within affected villages some households suffer from a high incidence of malignant mesothelioma whereas others do not.

The researchers tested whether affected villages and households are exposed to a particularly carcinogenic type of erionite. But by determining the crystal structure of the rock using X-ray diffraction, they found that the composition of erionite is the same in affected and unaffected villages and in erionite-rich regions of the United States.

The authors then became interested in whether genetics might have a role. They constructed 18 pedigrees from 'Old' Saridihir and 3 each from Karain and Tuzkoy. They found that when a member of a family with a high incidence of malignant mesothelioma marries into a family with no history of the disease, their descendents develop malignant mesothelioma. Furthermore, people who marry into families with high levels of malignant mesothelioma only develop the disease if they themselves are from an affected family. Their findings provide the first indication that genetics influences the development of mineral-fibre carcinogenesis.

But the disease is not caused by genetics alone. Individuals from high-incidence families born and raised outside 'Old' Sarihidir do not develop malignant mesothelioma, although longer follow-up studies will be needed to confirm this. Instead, the authors conclude that the Turkish epidemic of malignant mesothelioma is caused by a combination of genetic predisposition and environmental factors. The identification of the genes that are involved in this predisposition will shed light on why so few of the people exposed to carcinogenic mineral fibres develop disease.

References

ORIGINAL RESEARCH PAPER Dogan, A. U. et al. Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey. Cancer Res. 66, 5063–5068 (2006)