NLRP1 polymorphisms in patients with asbestos-associated mesothelioma

Alessandra Pontillo, Martina Ghirardelli, Iva Maestri, Rosa Rinaldi, Renzo Boldorini, Mauro Tognon, Massimo Bovenzi, Sergio Crovella, Manola Comar

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)25
Number of pages1
JournalInfectious Agents and Cancer
DOIs
Publication statusAccepted/In press - Oct 2 2012

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Asbestos
Mesothelioma
Alleles
Inflammasomes
Single Nucleotide Polymorphism
Interleukins
Alveolar Macrophages
Blood Donors
Interleukin-1beta
Italy
Healthy Volunteers
Epithelial Cells
Apoptosis
Morbidity
Lung
Survival
Malignant Mesothelioma
Incidence
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Infectious Diseases

Cite this

Pontillo, A., Ghirardelli, M., Maestri, I., Rinaldi, R., Boldorini, R., Tognon, M., ... Comar, M. (Accepted/In press). NLRP1 polymorphisms in patients with asbestos-associated mesothelioma. Infectious Agents and Cancer, 25. https://doi.org/10.1186/1750-9378-7-25

NLRP1 polymorphisms in patients with asbestos-associated mesothelioma. / Pontillo, Alessandra; Ghirardelli, Martina; Maestri, Iva; Rinaldi, Rosa; Boldorini, Renzo; Tognon, Mauro; Bovenzi, Massimo; Crovella, Sergio; Comar, Manola.

In: Infectious Agents and Cancer, 02.10.2012, p. 25.

Research output: Contribution to journalArticle

Pontillo, A, Ghirardelli, M, Maestri, I, Rinaldi, R, Boldorini, R, Tognon, M, Bovenzi, M, Crovella, S & Comar, M 2012, 'NLRP1 polymorphisms in patients with asbestos-associated mesothelioma', Infectious Agents and Cancer, pp. 25. https://doi.org/10.1186/1750-9378-7-25
Pontillo A, Ghirardelli M, Maestri I, Rinaldi R, Boldorini R, Tognon M et al. NLRP1 polymorphisms in patients with asbestos-associated mesothelioma. Infectious Agents and Cancer. 2012 Oct 2;25. https://doi.org/10.1186/1750-9378-7-25
Pontillo, Alessandra ; Ghirardelli, Martina ; Maestri, Iva ; Rinaldi, Rosa ; Boldorini, Renzo ; Tognon, Mauro ; Bovenzi, Massimo ; Crovella, Sergio ; Comar, Manola. / NLRP1 polymorphisms in patients with asbestos-associated mesothelioma. In: Infectious Agents and Cancer. 2012 ; pp. 25.
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AU - Pontillo, Alessandra

AU - Ghirardelli, Martina

AU - Maestri, Iva

AU - Rinaldi, Rosa

AU - Boldorini, Renzo

AU - Tognon, Mauro

AU - Bovenzi, Massimo

AU - Crovella, Sergio

AU - Comar, Manola

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N2 - 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.

AB - 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.

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