NLRP1 polymorphisms in patients with asbestos-associated mesothelioma

Our plain-English summary of NLRP1 polymorphisms in patients with asbestos-associated mesothelioma, by M. Girardelli, I. Maestri, R.R. Rinaldi, et al (Infectious Agents and Cancer, 2012).

The study

• Authors: M. Girardelli, I. Maestri, R.R. Rinaldi, M. Tognon, R. Boldorini, M. Bovenzi, S. Crovella, M. Comar
• Journal: Infectious Agents and Cancer
• Published: 2012;7(1):25
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This genetic association study from north-eastern Italy asked whether variants in two inflammation-related genes, NLRP1 and NLRP3, differed between people with and without mesothelioma. The authors tested blood from 134 patients with malignant pleural mesothelioma collected in 2009–2011. Of these, 69 had ascertained occupational asbestos exposure and 65 had no documented exposure. They also tested 101 healthy people from the same area with previous risk of environmental asbestos exposure, and 256 healthy blood donors from outside the area. The article does not name asbestos fiber types. None of the four variants differed significantly between all patients and the blood donors. Comparing exposed patients with exposed healthy people, the NLRP1 rs12150220 T allele had a frequency of 0.55 versus 0.41 (odds ratio 1.79, 95% confidence interval 1.13-2.85, p=0.011). One NLRP1 variant combination (the A–A haplotype) was less frequent in exposed patients than in exposed healthy people (0.40 versus 0.56; odds ratio 0.52, 95% confidence interval 0.33-0.83, p=0.004). The NLRP3 variants showed no association. The authors called their results preliminary and concluded that NLRP1 is a novel factor possibly involved in mesothelioma development.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Genetic association (case-control) study comparing gene variant frequencies in blood samples from mesothelioma patients and healthy controls
• Who was studied: Four groups were studied. The first was 134 Caucasian patients with malignant pleural mesothelioma from north-eastern Italy (Trieste, Ferrara), collected 2009–2011: 112 males and 22 females, average age 66. Of these, 69 had ascertained occupational asbestos exposure (MMAE) and 65 had no documented exposure (MMAF). The second was 101 healthy subjects from the same area with previous risk of environmental asbestos exposure (HCAE): 84 males and 17 females, average age 44. The third was 256 healthy blood donors (HC) not related to the patients' geographic area: 118 males and 138 females, average age 42.
• Exposure: Asbestos exposure, with no fiber types named. The patient group was classified as having ascertained occupational asbestos exposure or no documented exposure, based on records of the Local Mesothelioma Registry affiliated to the Italian National Mesothelioma Registry (ReNaM). The exposed healthy controls had a previous risk of environmental asbestos exposure. The genetic factors studied were two NLRP1 variants (rs2670660, rs12150220) and two NLRP3 variants (rs35829419, rs10754558).
• Main results:
  • None of the four variants differed significantly between all 134 mesothelioma patients and the 256 healthy blood donors.
  • The NLRP1 rs12150220 T allele was more frequent in asbestos-exposed patients (0.55) than in asbestos-exposed healthy controls (0.41): p=0.011, OR=1.79, 95% CI 1.13-2.85.
  • The NLRP1 rs2670660 G allele was more frequent in exposed patients than in exposed healthy controls (0.55 versus 0.43, p=0.027). This was not significant after Bonferroni correction.
  • The NLRP1 A–A haplotype was less frequent in exposed patients than in exposed healthy controls: 0.40 versus 0.56, p=0.004, OR=0.52, 95% CI 0.33-0.83.
  • The two NLRP3 variants were not associated with mesothelioma when asbestos exposure was considered.
  • Exposed and unexposed mesothelioma patients did not differ significantly for any of the four variants.
• The authors' conclusion: The authors concluded that the NLRP3 variants were not involved in mesothelioma predisposition. They proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma.
• Limitations the authors state:
  • The authors described their results as preliminary and said deeper investigation will be needed.
  • The two NLRP3 variants analyzed may not represent the entire gene, so an association with NLRP3 cannot be definitively excluded.
  • No functional information exists about the NLRP1 variants studied.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, SV40, Alveolar Macrophage, Apoptosis.

Related studies

• NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy — V. Borelli, R.R. Moura, et al. (2015)
• NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases — A. Franko, K. Goricar, et al. (2020)
• A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma — S. Crovella, R.R. Moura, et al. (2018)
• Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β — A.S. Yazdi, G. Guarda, et al. (2010)
• Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism — J. Palomäki, E. Välimäki, et al. (2011)
• Vimentin regulates activation of the NLRP3 inflammasome — G. dos Santos, M.R. Rogel, et al. (2015)

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