NLRP1 polymorphisms in patients with asbestos-associated mesothelioma

Infectious Agents and Cancer

Manola Comar⁷  Sergio Crovella⁷  Massimo Bovenzi³  Renzo Boldorini⁵  Mauro Tognon¹  Rosa R Rinaldi⁴  Iva Maestri⁶  Martina Girardelli² 

[1] Section of Cell Biology and Molecular Genetics, School of Medicine and Surgery, University of Ferrara, Ferrara, Italy;Institute for Maternal and Child Health–IRCCS “Burlo Garofolo”, Trieste, Italy;Clinical Unit of Occupational Medicine, University of Trieste, Trieste, Italy;Deartment of Laboratory Medicine, Operative Unit of Anatomy-Pathology, Sant’Anna University Hospital of Ferrara, Ferrara, Italy;Department of Medical Sciences, Faculty of Medicine, University of the Piemonte Orientale, Novara, Italy;Department of Experimental and Diagnostic Medicine, Pathology Unit of Pathologic Anatomy, Histology and Cytology University of Ferrara, Ferrara, Italy;Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, University of Trieste, Trieste, Italy

关键词: NLRP3;    NLRP1;    Inflammasome;    Asbestos;    Mesothelioma;   

Others  :  803412
DOI  :  10.1186/1750-9378-7-25

 received in 2012-09-04, accepted in 2012-10-01,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Girardelli et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Yang H, Testa JR, Carbone M: Mesothelioma epidemiology, carcinogenesis, and pathogenesis. Curr Treat Options Oncol 2008, 9(2-3):147-157.
• [2]Goodman JE, Nascarella MA, Valberg PA: Ionizing radiation: a risk factor for mesothelioma. Cancer Causes Contro. 2009, 20:1237-1254.
• [3]Weiner SJ, Neragi-Miandoab S: Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors. J Cancer Res Clin Oncol 2009, 135:15-27.
• [4]Dogan AU, Baris Y, Dogan M, Emri S, Steele I, Elmishad AG: Genetic predisposition to fiber carcinogenesis causes a mesotheliom epidemic in turkey. Cancer Res 2006, 66:5063-5068.
• [5]Villani AC, Lemire M, Fortin G, Louis E, Silverberg MS, Collette C, Baba N, Libioulle C, Belaiche J, Bitton A, Gaudet D, Cohen A, Langelier D, Fortin PR, Wither JE, Sarfati M, Rutgeerts P, Rioux JD, Vermeire S, Hudson TJ, Franchimont D: Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat Genet 2009, 41(1):71-76.
• [6]Pontillo A, Brandao L, Guimaraes R, Segat L, Araujo J, Crovella S: Two SNPs in NLRP3 gene are involved in the predisposition to type-1 diabetes and celiac disease in a pediatric population from northeast Brazil. Autoimmunity 2010, 43(8):583-589.
• [7]Qi F, Carbone M, Yang H, Gaudino G: Simian virus 40 transformation, malignant mesothelioma and brain tumors. Expert Rev Respir Med 2011, 5(5):683-697.
• [8]Robinson C, Van Bruggen I, Segal A, Dunham M, Sherwood A, Koentgen F, Robinson BW, Lake RA: A novel SV40 Tag transgenic model of asbestos-induced mesothelioma: malignant transformation is dose dependent. Cancer Res 2006, 15:10786-10794.
• [9]Foddis R, De Rienzo A, Broccoli D, Bocchetta M, Stekala E, Rizzo P, Tosolini A, Grobelny JV, Jhanwar SC, Pass HI, Testa JR, Carbone M: SV40 infectious induces telomerase activity in human mesothelial cells. Oncogene 2002, 21:1434-1442.
• [10]Pontillo A, Brandão LA, Guimarães RL, Segat L, Athanasakis E, Crovella S: A 3’UTR SNP in NLRP3 gene is associated with susceptibility to HIV-1 infection. J Acquir Immune Defic Syndr 2010, 54(3):236-240.
• [11]Jin Y, Mailloux CM, Gowan K, Riccardi SL, LaBerge G, Bennett DC, Fain PR, Spritz RA: NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007, 356(12):1216-1225.
• [12]Magitta NF, Bøe Wolff AS, Johansson S, Skinningsrud B, Lie BA, Myhr KM, Undlien DE, Joner G, Njølstad PR, Kvien TK, Førre Ø, Knappskog PM, Husebye ES: A coding polymorphism in NALP1 confers risk for autoimmune Addison’s disease and type 1 diabetes. Genes Immun 2009, 10(2):120-124.
• [13]Pontillo A, Catamo E, Arosio B, Mari D, Crovella S: NALP1/NLRP1 Genetic variants are associated with Alzheimer disease. Alzheimer Dis Assoc Disord 2011, 26(3):277-281.
• [14]Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L, Martinon F, van Bruggen R, Tschopp J: Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem 2007, 55(5):443-452.
• [15]Comar M, Zanotta N, Pesel G, Visconti P, Maestri I, Rinaldi R, Crovella S, Cortale M, De Zotti R: Bovenzi M Asbestos and SV40 in malignant pleural mesothelioma from a hyperendemic area of north-eastern Italy. Tumori 2012, 98(2):210-214.
• [16]Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, Xu C, Kress CL, Bailly-Maitre B, Li X, Osterman A, Matsuzawa S, Terskikh AV, Faustin B, Reed JC: Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 2007, 129(1):45-56.
• [17]Wang Y, Faux SP, Hallden G, Kirn DH, Houghton CE, Lemoine NR, Patrick G: Interleukin-1beta and tumour necrosis factor-alpha promote the transformation of human immortalised mesothelial cells by erionite.ù. Int J Oncol 2004, 25(1):173-178.
• [18]Krelin Y, Voronov E, Dotan S, Elkabets M, Reich E, Fogel M, Huszar M, Iwakura Y, Segal S, Dinarello CA, Apte RN: Interleukin-1beta-driven inflammation promotes the development and invasiveness of chemical carcinogen-induced tumors. Cancer Res 2007, 67(3):1062-1071.
• [19]Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J: Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 2008, 320(5876):674-677.
• [20]Verma D, Lerm M, Blomgran Julinder R, Eriksson P, Söderkvist P, Särndahl E: Gene polymorphisms in the NLRP3 inflammasome Are associated with interleukin-1 production and severe inflammation. Arthritis Rheum 2008, 58(3):888-894.
• [21]Kastbom A, Johansson M, Verma D, Söderkvist P, Rantapää-Dahlqvist S: The CARD8 p.C10X polymorphism associates with the inflammatory activity in early rheumatoid arthritis. Ann Rheum Dis 2009, 69(4):723-726.
• [22]Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, Génin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, André F, Lidereau R, McLaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L: Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 2009, 15(10):1170-1178.
• [23]Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H: Malignant mesothelioma: facts, myths, and hypotheses. J Cell Physiol 2012, 227(1):44-58.
• [24]Carbone M, Yang H: Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin Cancer Res 2012, 18(3):598-604.
• [25]Okamoto M, Liu W, Luo Y, Tanaka A, Cai X, Norris DA, Dinarello CA, Fujita M: Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase-1 processing and secretion of interleukin-1beta. J Biol Chem 2010, 285(9):6477-6488.
• [26]Aymeric L, Apetoh L, Ghiringhelli F, Tesniere A, Martins I, Kroemer G, Smyth MJ, Zitvogel L: Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 2010, 70(3):855-858.
• [27]Ostrand-Rosenberg S, Sinha P: Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 2009, 182(8):4499-4506.
• [28]Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 2001, 357(9255):539-545.
• [29]Balkwill F, Coussens LM: Cancer: an inflammatory link. Nature 2004, 431(7007):405-406.
• [30]Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y: The new world health organization classification of lung tumours. Eur Respir J 2001, 18(6):1059-1068.
• [31]Cox DG, Canzian F: Genotype transposer: automated genotype manipulation for linkage disequilibrium analysis. Bioinformatics 2001, 17:738-739.
• [32]Barrett JC, Fry B, Maller J, et al.: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21:263-265.
• [33]Lewis CM: Genetic association studies: design, analysis and interpretation. Brief Bioinform 2002, 3:146-153.