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.

A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.

The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.

[Respiratory diseases in a group of traffic police officers: results of a 5-year follow-up]. / Patologie delle vie aeree in vigili urbani: risultati di un follow-up di 5 anni.

BACKGROUND: Exposure to urban pollution may cause respiratory diseases in traffic policemen, especially in very polluted cities. The aim of this study was to investigate respiratory symptoms and pulmonary function in traffic police officers in a 5-year follow-up. METHODS: A 5-year follow-up on FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), and respiratory symptoms was performed on 290 traffic policemen (90.9% of participation rate, mean age 39 +/- 8.3 years, seniority of work 11.4 +/- 8.2 years). RESULTS: Upper respiratory symptoms were reported by the 28% of traffic policemen assigned to traffic control and by the 11% of administrative workers (p = 0.006). Neither in the 1st control (ORc 1.1; IL 95% 0.6-2.3) nor in the follow-up, did ORL evaluation show any difference between the two groups, after having controlled for smoking habits (Mac Nemar test p > 0.05). The follow up on FEV1 and FVC did not show an accelerated decline in traffic policemen assigned to traffic control as compared to administrative police workers. These data suggest the need to follow-up this cohort, evaluating symptoms and respiratory function for a longer period of time, in order to better understand the role of road traffic pollution in inducing respiratory diseases.