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Open Access Research article

NLRP1 polymorphisms in patients with asbestos-associated mesothelioma

Martina Girardelli1, Iva Maestri3, Rosa R Rinaldi4, Mauro Tognon5, Renzo Boldorini6, Massimo Bovenzi7, Sergio Crovella2 and Manola Comar2*

Author Affiliations

1 Institute for Maternal and Child Health–IRCCS “Burlo Garofolo”, Trieste, Italy

2 Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, University of Trieste, Trieste, Italy

3 Department of Experimental and Diagnostic Medicine, Pathology Unit of Pathologic Anatomy, Histology and Cytology University of Ferrara, Ferrara, Italy

4 Deartment of Laboratory Medicine, Operative Unit of Anatomy-Pathology, Sant’Anna University Hospital of Ferrara, Ferrara, Italy

5 Section of Cell Biology and Molecular Genetics, School of Medicine and Surgery, University of Ferrara, Ferrara, Italy

6 Department of Medical Sciences, Faculty of Medicine, University of the Piemonte Orientale, Novara, Italy

7 Clinical Unit of Occupational Medicine, University of Trieste, Trieste, Italy

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Infectious Agents and Cancer 2012, 7:25  doi:10.1186/1750-9378-7-25

Published: 2 October 2012

Abstract

Background

An 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.

Methods

134 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.

Results

While 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).

Conclusion

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

Keywords:
Mesothelioma; Asbestos; Inflammasome; NLRP1; NLRP3