NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy

Our plain-English summary of NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy, by V. Borelli, R.R. Moura, E. Trevisan, et al (Infectious Agents and Cancer, 2015).

The study

• Authors: V. Borelli, R.R. Moura, E. Trevisan, S. Crovella
• Journal: Infectious Agents and Cancer
• Published: 2015;10:26
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

NRLP1 (rs12150220, rs9889625, rs9900356, rs6502867, rs2670660) and NLRP3 (rs35829419, rs10754558) polymorphisms have been analyzed in 69 subjects with documented asbestos exposure and death for malignant pleural mesothelioma and 59 patients with documented asbestos exposure but death for other causes, all from a North East Italy. No association was found between NLRP1 and NLRP3 polymorphisms and susceptibility to develop mesothelioma using the general, dominant or recessive models. Also haplotype analysis did not reveal any significant association with mesothelioma. Our findings, being controversial with respect to another study on Italian patients, do suggest the need of further studies to unravel the contribution of NLRP1 and NLRP3 in susceptibility to mesothelioma.

In plain English

This letter to the editor reported a genetic study of 128 people who died between 1980 and 2000 in Monfalcone, North East Italy, an industrial area the authors described as having endemic asbestos exposure. All had documented asbestos exposure: 69 died of malignant pleural mesothelioma and 59, used as controls, died of causes other than mesothelioma and other asbestos-related diseases. Using DNA extracted from autopsy heart tissue, the authors tested five variants of the NLRP1 gene and two of the NLRP3 gene. Their aim was to repeat an earlier study by Girardelli and colleagues that had linked one NLRP1 variant, rs12150220, to mesothelioma in Italian patients. No variant, and no combination of variants (haplotype), was associated with mesothelioma. People with the rs12150220 T/T genotype had an odds ratio of 1.13 (95% confidence interval 0.45 to 2.81) compared with the A/A genotype. Computer prediction tools indicated no damaging effect for rs12150220. The authors concluded that their study did not confirm a role for NLRP1 in mesothelioma susceptibility and called for studies of more people.

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: Letter to the editor reporting a genetic association study comparing asbestos-exposed people who died of mesothelioma with asbestos-exposed controls. It used archived autopsy tissue and was intended to replicate an earlier study (Girardelli et al.).
• Who was studied: 128 deceased people from Monfalcone, North East Italy, who died 1980 to 2000. 69 had documented asbestos exposure and died of malignant pleural mesothelioma (AEM group). 59 had documented asbestos exposure but died of causes other than mesothelioma and other asbestos-related diseases (AENM group, controls).
• Exposure: Documented asbestos exposure in all subjects. Fiber types are not named. For the control group, exposure was confirmed by pleural hyaline plaque at autopsy (grade 2 or higher), asbestos bodies in routine lung sections, and, for most cases, asbestos body counts of 10,000 or more per gram of dry lung tissue. The genetic factors studied were five NLRP1 and two NLRP3 polymorphisms.
• Main results:
  • No association was found between the NLRP1 or NLRP3 polymorphisms and susceptibility to mesothelioma under the general, dominant or recessive models.
  • Haplotypes were found: two blocks in NLRP1 and one in NLRP3. Haplotype frequencies in the mesothelioma and control groups showed no association with susceptibility to the disease.
  • For NLRP1 rs12150220, the T/T genotype was found in 20 of 69 mesothelioma subjects and 16 of 59 controls. The odds ratio was 1.13 (95% CI 0.45 to 2.81, p = 0.9849) compared with the A/A reference genotype.
  • The association with mesothelioma for rs12150220 and the rs12150220 to rs2670660 haplotype reported by Girardelli et al. was not replicated.
  • All markers were in Hardy-Weinberg Equilibrium except NLRP1 rs9900356 in the mesothelioma group and NLRP3 rs35829419 in both groups.
  • Computer (in silico) prediction with SIFT (0.16) and Polyphen (0.415) indicated no damaging effect for NLRP1 rs12150220.
• The authors' conclusion: The authors concluded that their study, in patients and controls with homogeneous asbestos exposure, does not confirm involvement of the NLRP1 inflammasome in susceptibility to mesothelioma in Italian patients. They said larger numbers of individuals need to be analyzed.
• Limitations the authors state:
  • The authors acknowledged the limitations of in silico prediction of variant function and said the hypothesized role of rs12150220 should be verified functionally.
  • The authors pointed to the need to analyze a larger number of individuals, such as those used in genome-wide studies.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Autopsy, Asbestos Exposure, Pleural Mesothelioma.

Related studies

• Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study — S. Crovella, A.M. Bianco, et al. (2016)
• NLRP1 polymorphisms in patients with asbestos-associated mesothelioma — M. Girardelli, I. Maestri, et al. (2012)
• Life after first-line chemotherapy in malignant pleural mesothelioma: a North-East England experience — J. Steer, G. Bough, et al. (2010)
• 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)
• NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases — A. Franko, K. Goricar, et al. (2020)
• Tissue burden of asbestos in nonoccupationally exposed individuals from east Texas — R.F. Dodson, M.G. Williams, et al. (1999)

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