Melaiu Ombretta, Gemignani Federica, Landi Stefano
Department of Biology, University of Pisa, Pisa, Italy.
J Thorac Dis. 2018 Jan;10(Suppl 2):S246-S252. doi: 10.21037/jtd.2017.10.41.
Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity whose main risk factor is exposure to asbestos. However, it has been shown that only a minority of exposed people develops MPM. In fact, the incidence among professionally exposed workers was shown to vary between 0.5% and 18.0%. Various hints suggested that other important cofactors could play a role, in particular the genetic susceptibility. Impressive is the case of Cappadocians families exposed to erionite and affected by an "epidemic" of MPM with about half of the inhabitants dying for the disease. However, no results for a "Cappadocia" gene of susceptibility to MPM have been obtained yet and more studies are needed. Among asbestos-exposed workers, several studies reported familial cases of MPM, suggesting that heredity could be important in the tumor development. However, large studies on familial clusters showed only weak increased risks that could be attributable also to indirect exposures in a contaminated household. Moreover, the risk of developing MPM is increased of a limited extent among people exposed to asbestos with a positive history of familial cancers. A particular is represented by carriers of germline mutations within gene. In families and in animal models, mutations within are strongly predisposing to develop MPM. However, also other types of cancer (such as uveal melanoma) are present, thus mutations are considered as responsible for a hereditary form of a multi-cancer syndrome. In any case, among sporadic MPM, the prevalence of germline mutations is negligible. Finally, genetic studies highlighted the presence of low-risk susceptibility alleles, such as those within or . Two different genome-wide association studies could not find positive associations reaching the genome-wide statistical significance threshold, however, both were concordant in showing a weak signal within the gene region. Overall, it could be concluded that, as for other types of sporadic cancers, the susceptibility to develop MPM following asbestos exposure is modulated moderately by the individual genetic background. Further studies on larger series could help in a better characterization of more genes predisposing to MPM, being this tumor a rare disease.
恶性胸膜间皮瘤（MPM）是一种胸膜腔癌症，其主要危险因素是接触石棉。然而，研究表明，只有少数接触石棉的人会患上MPM。事实上，职业接触石棉的工人中MPM的发病率在0.5%至18.0%之间。各种线索表明，其他重要的辅助因素可能起作用，特别是遗传易感性。令人印象深刻的是卡帕多西亚人的家庭，他们接触了毛沸石并受到MPM“流行病”的影响，约一半居民死于这种疾病。然而，尚未获得对MPM易感的“卡帕多西亚”基因的研究结果，还需要更多的研究。在接触石棉的工人中，多项研究报告了MPM的家族病例，这表明遗传因素在肿瘤发展中可能很重要。然而，关于家族聚集性的大型研究仅显示出微弱的风险增加，这也可能归因于受污染家庭中的间接接触。此外，在有家族癌症病史且接触石棉的人群中，患MPM的风险仅在有限程度上增加。一个特殊情况是该基因种系突变的携带者。在家族和动物模型中，该基因内的突变极易引发MPM。然而，也存在其他类型的癌症（如葡萄膜黑色素瘤），因此该基因突变被认为是一种遗传性多癌综合征的病因。无论如何，在散发性MPM中，种系该基因突变的患病率可忽略不计。最后，基因研究突出了低风险易感等位基因的存在，如该基因或其他基因内的等位基因。两项不同的全基因组关联研究均未发现达到全基因组统计学意义阈值的阳性关联，但两者都一致显示该基因区域内有微弱信号。总体而言，可以得出结论，与其他类型的散发性癌症一样，石棉暴露后患MPM的易感性受到个体遗传背景的适度调节。鉴于这种肿瘤是一种罕见疾病，对更大样本系列的进一步研究可能有助于更好地鉴定更多易患MPM的基因。
