Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes

ABSTRACT

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.

KEYWORDS:

• Mesothelioma
• lung cancer
• formalin-fixed and paraffin-embedded tissue samples
• inflammasome
• hephaestin
• iron
• polymorphisms
• asbestos exposure

Acknowledgments

We thank all the staff of the Monfalcone’s Hospital Pathological Anatomy Unit for their valuable technical assistance. We thank also the Council for the management of Fondo del Lascito Carrara for the technical support.

Declaration of interest

All authors declare to have no conflict of interest.

Supplementary material

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Additional information

Funding

The authors acknowledge a grant from Regione Autonoma Friuli-Venezia Giulia, Assessorato alla Salute e Protezione Sociale, LR 22/2001 (decree 1124/SPS, 09/20/2016, N° 1299) and from Italian League for the Fight Against Cancer (LILT), Gorizia section (Bando di Ricerca sanitaria 2017-programma 5 per mille anno 2015);Regione Autonoma Friuli-Venezia Giulia, Assessorato alla Salute e Protezione Sociale, LR 22/2001 [decree 1124/SPS, 09/20/2016, N° 1299];Italian League for the Fight Against Cancer Lega Italiana per la Lotta contro i Tumori (LILT) [Bando di Ricerca sanitaria 2017-programma 5 per mille];