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NLRP1 polymorphisms in patients with asbestos-associated mesothelioma

Martina Girardelli1, Iva Maestri, Rosa R Rinaldi

  • 1Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", University of Trieste, Trieste, Italy. comar@burlo.trieste.it.

Infectious Agents and Cancer
|October 4, 2012
PubMed
Abstract

Insights

Genetic variations in NLRP1 influence susceptibility to asbestos-induced malignant mesothelioma (MM). Specific NLRP1 polymorphisms, particularly rs12150220, were associated with an increased risk of developing MM in individuals exposed to asbestos.

Area of Science:

  • Genetics
  • Immunology
  • Environmental Health

Background:

  • Malignant mesothelioma (MM) incidence rises with low asbestos exposure, suggesting cofactors.
  • Inflammatory responses mediated by inflammasomes, particularly IL-1ß, are implicated in asbestos-induced MM.
  • NLRP3 and NLRP1 inflammasomes are key in sensing asbestos and regulating immune responses.

Purpose of the Study:

  • To investigate the role of NLRP1 and NLRP3 polymorphisms in susceptibility to asbestos-induced mesothelioma.
  • To evaluate genetic predisposition in individuals from a high-incidence area for MM.

Main Methods:

  • Genotyping of 134 Italian mesothelioma patients (asbestos-related and non-related) and 357 controls (healthy donors and asbestos-exposed individuals).
  • Analysis of specific single nucleotide polymorphisms (SNPs) in NLRP1 (rs2670660, rs12150220) and NLRP3 (rs35829419, rs10754558).

Main Results:

  • NLRP3 polymorphisms showed no association with mesothelioma.
  • The NLRP1 rs12150220 allele T was significantly more prevalent in asbestos-exposed mesothelioma patients, indicating a predisposition.
  • Combined NLRP1 rs2670660 and rs12150220 alleles amplified the predisposition effect.

Conclusions:

  • NLRP3 SNPs are not implicated in mesothelioma predisposition.
  • NLRP1 polymorphisms represent a novel genetic factor potentially involved in the development of asbestos-induced mesothelioma.

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