| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p><it>NLRP3</it> inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1ß secretion while <it>NLRP1</it> 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 <it>NLRP3</it> and <it>NLRP1</it> polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM.</p> <p>Methods</p> <p>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 <it>NLRP1</it> (rs2670660 and rs12150220) and <it>NLRP3</it> (rs35829419 and rs10754558) polymorphisms.</p> <p>Results</p> <p>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 <it>NLRP1</it> rs2670660 allele was combined with the <it>NLRP1</it> rs12150220 allele (p=0.004; OR=0.52).</p> <p>Conclusion</p> <p>Although <it>NLRP3</it> SNPs was not involved in mesothelioma predisposition, these data proposed <it>NLRP1</it> as a novel factor possibly involved in the development of mesothelioma.</p>
|
|---|
