20.500.12556/RUL-185135 Genetic variability of immune checkpoints in asbestos-related diseases Background Asbestos exposure is associated with asbestos-related diseases such as pleural plaques, asbestosis, lung cancer, malignant mesothelioma (MM), as well as several other types of cancer. Although the exact mechanism underlying the development of asbestos-related diseases is not yet fully understood, the immune system may play an important role. Immune checkpoints such as programmed cell death receptor 1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) regulate immune responses and are crucial for maintaining immune tolerance, while defects in these mechanisms can lead to the development of cancer. The aim of present study was to investigate the association of polymorphisms in the immune checkpoint genes for PD-1 (PDCD1), PD-L1 (CD274), and CTLA-4 (CTLA4) with the risk of asbestos-related diseases. Subjects and methods We conducted a retrospective case-control study. The cases included individuals with asbestosis or pleural plaques and MM patients. The controls were asbestos-exposed subjects who did not develop asbestos-related diseases. All subjects were genotyped for PDCD1 (rs2227982, rs222798, rs10204525), CD274 (rs2297136, rs4143815, rs4742098) and CTLA4 (rs5742909, rs4553808, rs231775) polymorphisms using competitive allele-specific PCR. Statistical analysis was performed using logistic regression. Results Our study showed that the CTLA4 rs4553808 polymorphism was associated with a decreased risk of asbestosrelated diseases (OR = 0.34, 95% CI = 0.15-0.74, P = 0.007). Homozygous carriers of polymorphic rs4553808 G allele had a lower risk of developing pleural plaques as well as MM compared to the control group (OR = 0.28, 95% CI = 0.11-0.68, P = 0.01, and OR = 0.38, 95% CI = 0.16 -0.93, P = 0.03, respectively). However, carriers of polymorphic CTLA4 rs231775 GG genotype had a higher risk of developing MM compared to the group of subjects with pleural plaques (OR = 1.79, 95% CI = 1.10-2.89, P = 0.02). The other investigated polymorphisms were not associated with any of the asbestos-related diseases. Conclusions CTLA4 polymorphisms may play a role in the susceptibility for asbestos-related diseases. Our results may contribute to a better understanding of the pathogenesis and progression of asbestos-related diseases. asbestos malignant mesothelioma immune checkpoints single nucleotide polymorphism azbest omkologija true false true Association of Radiology and Oncology Angleški jezik Slovenski jezik Članek v reviji 2026-07-24 07:04:14 2026-07-24 09:21:18 2026-07-28 11:36:42 0000-00-00 00:00:00 2026 0 0 str. 271-281 iss. 2 Vol. 60 June 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006 1318-2099 10.2478/raon-2026-0035 284688387 RAZ_Zeljkovic_Irma_2026.pdf RAZ_Zeljkovic_Irma_2026.pdf 1 0DFE742E522DD2C6C95099F9008C8954 3d2f33d0f97a91f2e82fbec69a1c9806457ed5243a5d90fbf71744f8b8f9129e cf2f109d-872f-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=243360 https://reference-global.com/article/10.2478/raon-2026-0035 1 e29ec7b6-871c-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=243348 Medicinska fakulteta 0 0 0