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Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes.
Journal of Toxicology and Environmental Health, Part A ( IF 2.6 ) Pub Date : 2019-11-22 , DOI: 10.1080/15287394.2019.1694612
F Celsi 1, 2 , S Crovella 3, 4 , R R Moura 5 , M Schneider 6 , F Vita 6 , L Finotto 7 , G Zabucchi 2 , P Zacchi 2 , V Borelli 2
Affiliation  

Two of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an "asbestos-resistant exposed population". A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF, emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC "genetic signature" may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.

中文翻译:

胸膜间皮瘤和肺癌:石棉暴露和遗传变异在选定的铁代谢和炎症基因中的作用。

与石棉接触有关的两种主要的癌症疾病是恶性胸膜间皮瘤(MPM)和肺癌(LC)。除了接触石棉外,遗传因素还被认为与石棉相关的致癌作用和肺部遗传毒性有关。尽管已报道了与MPM易感性有关的遗传因素,但迄今为止,对单个遗传变异对石棉相关肺癌风险的影响仍然知之甚少。由于炎症和铁稳态的破坏是石棉暴露影响肺组织的标志,因此本研究旨在通过比较暴露于石棉的人群,调查铁代谢和炎性基因变异与易感性LC或MPM之间的关联。受LC影响的“ 类似于我们以前基于尸检的先导研究的回顾性方法被用于一组新的尸检样本中,从而使我们有可能通过在一组新的尸检样本中重复进行分析来证实先前在MPM上获得的发现。进一步证实了HEPH编码SNP的保护作用。此外,FTH1或TF中的两个非编码SNP在来自MPM受试者同一地理区域的LC暴露人群的新队列中发挥了相似的保护作用。NLRP1和NLRP3多态性之间没有关联,易患MPM和LC。可能需要进一步研究特定的MPM和LC“遗传标记”,以拓宽我们对导致MPM和LC的遗传格局的认识。类似于我们以前基于尸检的先导研究的回顾性方法被用于一组新的尸检样本,从而使我们有可能通过在一组新的尸检样本中重复进行分析来证实MPM先前的发现。进一步证实了HEPH编码SNP的保护作用。此外,FTH1或TF中的两个非编码SNP在来自MPM受试者同一地理区域的LC暴露人群的新队列中发挥了相似的保护作用。NLRP1和NLRP3多态性之间没有关联,易患MPM和LC。可能需要进一步研究特定的MPM和LC“遗传标记”,以拓宽我们对导致MPM和LC的遗传格局的认识。
更新日期:2019-11-01
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