NLRP1 polymorphisms in patients with asbestos-associated mesotheliomaReport as inadecuate




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Infectious Agents and Cancer

, 7:25

First Online: 02 October 2012Received: 04 September 2012Accepted: 01 October 2012

Abstract

BackgroundAn increasing incidence of malignant mesothelioma MM cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin IL-1 beta ß activated within the inflammasome complex.

NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1ß secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival-apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM.

Methods134 Italian patients with diagnosis of mesothelioma due MMAE, n=69 or not MMAF, n=65 to asbestos, 256 healthy Italian blood donors and 101 Italian healthy subjects exposed to asbestos HCAE were genotyped for NLRP1 rs2670660 and rs12150220 and NLRP3 rs35829419 and rs10754558 polymorphisms.

ResultsWhile NLRP3 SNPs were not associated to mesothelioma, the NLRP1 rs12150220 allele T was significantly more frequent in MMAE 0.55 than in HCAE 0.41 p=0.011; OR=1.79 suggesting a predisponent effect of this allele on the development of mesothelioma. This effect was amplified when the NLRP1 rs2670660 allele was combined with the NLRP1 rs12150220 allele p=0.004; OR=0.52.

ConclusionAlthough NLRP3 SNPs was not involved in mesothelioma predisposition, these data proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma.

KeywordsMesothelioma Asbestos Inflammasome NLRP1 NLRP3 AbbreviationsMMMalignant mesothelioma

SNPSingle nucleotide polymorphism

MMAEMesothelioma due to asbestos exposure

MMAFMesothelioma asbestos free

HCHealthy controls

HCAEHealthy controls exposed to asbestos

NLRPNod like receptor protein.

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Author: Martina Girardelli - Iva Maestri - Rosa R Rinaldi - Mauro Tognon - Renzo Boldorini - Massimo Bovenzi - Sergio Crovella - M

Source: https://link.springer.com/article/10.1186/1750-9378-7-25



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