Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes
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.
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formalin-fixed and paraffin-embedded tissue samples;
Document Type: Research Article
Lega Italiana per la Lotta contro i Tumori (LILT), Italy
Institute for Maternal and Child Health, IRCCS Bo Garofolo, Trieste, Italy
Department of Genetics, Federal University of Pernambuco, Recife, Brazil
Laboratory of Pathological Anatomy, AAS2 “Bassa Friulana-Isontina” - S. Polo General Hospital, Monfalcone, Italy
Workplace Safety and Prevention, AAS2 “Bassa Friulana-Isontina” - S. Polo General Hospital, Monfalcone, Italy
Department of Life Sciences, University of Trieste, Trieste, Italy
October 18, 2019
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