Yang Haining, Testa Joseph R, Carbone Michele
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA.
Curr Treat Options Oncol. 2008 Jun;9(2-3):147-57. doi: 10.1007/s11864-008-0067-z. Epub 2008 Aug 15.
The incidence of mesothelioma has gone from almost none to the current 2500-3000 cases per year in the USA. This estimate is an extrapolation based on information available from the Surveillance, Epidemiology and End Results (SEER) Program that collects information on approximately 12% of the US population. Mesothelioma is a cancer that is linked to exposure to carcinogenic mineral fibers. Asbestos and erionite have a proven causative role; the possible role of other mineral fibers in causing mesothelioma is being investigated. Asbestos is considered the main cause of mesothelioma in the US and in the Western world. The capacity of asbestos to induce mesothelioma has been linked to its ability to cause the release of TNF-alpha (that promotes mesothelial cells survival), other cytokines and growth factors, and of mutagenic oxygen radicals from exposed mesothelial cells and nearby macrophages. Some investigators proposed that as a consequence of the regulations to prevent exposure and to forbid and/or limit the use of asbestos, the incidence of mesothelioma in the US (and in some European countries) should have started to decline before or around the year 2000, and sharply decline thereafter. Unfortunately, there are no data available yet to support this optimistic hypothesis. Simian virus 40 (SV40) infection and radiation exposure are additional causes, although their contribution to the overall incidence of mesothelioma is unknown. Recent data from several laboratories indicate that asbestos exposure and SV40 infection are co-carcinogens in causing mesothelioma in rodents and in causing malignant transformation of human mesothelial cells in tissue culture. An exciting new development comes from the discovery that genetic susceptibility to mineral fiber carcinogenesis plays a critical role in the incidence of this cancer in certain families. It is hoped that the identification of this putative mesothelioma gene will lead to novel mechanistically driven preventive and therapeutic approaches.
在美国，间皮瘤的发病率已从几乎为零升至目前每年2500 - 3000例。这一估计是基于监测、流行病学和最终结果（SEER）项目提供的信息进行的推断，该项目收集了约12%美国人口的信息。间皮瘤是一种与接触致癌矿物纤维有关的癌症。石棉和毛沸石已被证实具有致病作用；其他矿物纤维在引发间皮瘤方面的可能作用正在研究中。在美国和西方世界，石棉被认为是间皮瘤的主要病因。石棉诱发间皮瘤的能力与其促使肿瘤坏死因子 -α（促进间皮细胞存活）、其他细胞因子和生长因子以及来自暴露的间皮细胞和附近巨噬细胞的诱变氧自由基释放的能力有关。一些研究人员提出，由于预防接触以及禁止和/或限制使用石棉的相关规定，美国（以及一些欧洲国家）间皮瘤的发病率在2000年之前或前后应该已经开始下降，并在之后急剧下降。不幸的是，目前尚无数据支持这一乐观假设。猿猴病毒40（SV40）感染和辐射暴露是另外的病因，尽管它们对间皮瘤总体发病率的贡献尚不清楚。几个实验室的最新数据表明，石棉暴露和SV40感染在导致啮齿动物患间皮瘤以及在组织培养中导致人源间皮细胞恶性转化方面是共同致癌物。一个令人兴奋的新进展来自于发现对矿物纤维致癌作用的遗传易感性在某些家族这种癌症的发病率中起关键作用。希望鉴定出这个假定的间皮瘤基因将带来新的基于机制的预防和治疗方法。
