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纤维致癌的遗传易感性导致土耳其间皮瘤流行。

Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey.

作者信息

Dogan A Umran, Baris Y Izzettin, Dogan Meral, Emri Salih, Steele Ian, Elmishad Amira G, Carbone Michele

机构信息

Department of Geological Engineering, Ankara University, Ankara, Turkey.

出版信息

Cancer Res. 2006 May 15;66(10):5063-8. doi: 10.1158/0008-5472.CAN-05-4642.

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.

摘要

在西方世界,恶性间皮瘤常与接触石棉有关。它是一种相对罕见的癌症,在美国每年导致约2500人死亡,在英国每年导致约1000人死亡。相比之下,在土耳其卡帕多西亚地区图兹科伊、卡兰和“老”萨里希迪尔等村庄出生的人中,约50%的死亡是由恶性间皮瘤引起的。这种流行病被归因于接触毛沸石,这是一种在土耳其该地区常见的纤维状沸石矿物。在这三个村庄中,恶性间皮瘤在某些房屋中出现,而在其他房屋中则没有。假设是某些房屋中存在一种独特且更具致癌性的毛沸石,导致了恶性间皮瘤。我们确定了来自恶性间皮瘤村庄的毛沸石的X射线衍射图谱和晶体结构,并将结果与来自附近非恶性间皮瘤村庄以及美国的毛沸石样本进行了比较。我们发现在卡帕多西亚村庄,无论有无恶性间皮瘤流行,无论恶性间皮瘤发病率高或低的家庭中,以及在美国,都存在相同类型的毛沸石。对这三个恶性间皮瘤村庄的家谱研究表明,恶性间皮瘤在某些家族中普遍存在,而在其他家族中则没有。当高风险的恶性间皮瘤家庭成员与无该病家族史的人结婚时,其后代会出现恶性间皮瘤。在恶性间皮瘤村庄以外出生和长大的具有遗传易感性的家庭成员似乎不会患恶性间皮瘤。总之,家谱和矿物学研究表明,恶性间皮瘤流行是由遗传易感性个体接触毛沸石引起的。这是首次表明遗传学对矿物纤维致癌作用有影响。

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