Genetic variability of immune checkpoints in asbestos-related diseases

Characteristic	Category/unit	No disease (N = 78)	Pleural plaques (N = 376)	Asbestosis (N = 151)	MM (N = 297)	P
Sex	Male N (%)	57 (73.1)	259 (68.9)	117 (77.5)	219 (73.7)	0.214^a
	Female N (%)	21 (26.9)	117 (31.1)	34 (22.5)	78 (26.3)
Age	Median (25%–75%)	53.2 (47.7–59.5)	54.9 (48.8–62.7)	59.1 (51.2–66.0)	66.0 (59.5–73.0)	<0.001^b
Smoking	No N (%)	43 (55.1)	187 (49.7)	73 (48.3)	161 (55.7) [8]	0.325^a
	Yes N (%)	35 (44.9)	189 (50.3)	78 (51.7)	128 (44.3)

1 The number of missing data is presented in [].

1a Fisher exact test;

1b Kruskal Wallis test; MM - malignant mesothelioma

TABLE 2.

Allele frequencies in the investigated subject groups

Protein (Gene)	SNP	Genotype	Controls	Pleural plaques	Asbestosis	MM
Protein (Gene)	SNP	Genotype	N (%)	N (%)	N (%)	N (%)
PD-1 (PDCD1)	rs2227982	CC	74 (94.9)	356 (95.4)	144 (95.4)	287 (96.6)
		CT	4 (5.1)	17 (4.6)	7 (4.6)	9 (3.0)
		TT	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.3)
		CT+TT	4 (5.1)	17 (4.6)	7 (4.6)	10 (3.4)
PD-1 (PDCD1)	rs2227981	CC	28 (36.4)	112 (30.1)	54 (35.8)	95 (32.0)
		CT	34 (44.2)	191 (51.3)	72 (47.7)	150 (50.5)
		TT	15 (19.5)	69 (18.5)	25 (16.6)	52 (17.5)
		CT+TT	49 (63.6)	260 (69.9)	97 (64.2)	202 (68.0)
PD-1 (PDCD1)	rs10204525	GG	59 (77.6)	295 (78.5)	120 (79.5)	248 (83.5)
		GA	15 (19.7)	75 (19.9)	30 (19.9)	48 (16.2)
		AA	2 (2.6)	6 (1.6)	1 (0.7)	1 (0.3)
		GA+AA	17 (22.4)	81 (21.5)	31 (20.5)	49 (16.5)
PD-L1 (CD274)	rs2297136	GG	15 (19.2)	77 (20.8)	41 (27.2)	54 (18.2)
		GA	43 (55.1)	180 (48.5)	72 (47.7)	169 (56.9)
		AA	20 (25.6)	114 (30.7)	38 (25.2)	74 (24.9)
		GA+AA	63 (80.8)	294 (79.2)	110 (72.8)	243 (81.8)
PD-L1 (CD274)	rs4143815	GG	39 (50.0)	159 (42.3)	65 (43.0)	134 (45.1)
		GC	32 (41.0)	162 (43.1)	66 (43.7)	135 (45.5)
		CC	7 (9.0)	55 (14.6)	20 (13.2)	28 (9.4)
		GC+CC	39 (50.0)	217 (57.7)	86 (57.0)	163 (54.9)
PD-L1 (CD274)	rs4742098	AA	43 (55.8)	189 (50.30)	76 (50.7)	160 (53.9)
		AG	27 (35.1)	147 (39.1)	64 (42.7)	117 (39.4)
		GG	7 (9.1)	40 (10.6)	10 (6.7)	20 (6.7)
		AG+GG	34 (44.2)	187 (49.7)	74 (49.3)	137 (46.1)
CTLA-4 (CTLA4)	rs4553808	AA	40 (51.9)	240 (63.8)	91 (60.3)	186 (62.8)
		AG	28 (36.4)	121 (32.2)	52 (34.4)	94 (31.8)
		GG	9 (11.7)	15 (4)	8 (5.3)	16 (5.4)
		AG+GG	37 (48.1)	136 (36.2)	60 (39.7)	110 (37.2)
CTLA-4 (CTLA4)	rs5742909	CC	54 (78.3)	302 (81.8)	117 (78.5)	237 (80.1)
		CT	13 (18.8)	63 (17.1)	28 (18.8)	54 (18.2)
		TT	2 (2.9)	4 (1.1)	4 (2.7)	5 (1.7)
		CT+TT	15 (21.7)	67 (18.2)	32 (21.5)	59 (19.9)
CTLA-4 (CTLA4)	rs231775	AA	39 (50.0)	181 (48.1)	71 (47.0)	128 (43.2)
		AG	28 (35.9)	157 (41.8)	65 (43.0)	120 (40.5)
		GG	11 (14.1)	38 (10.1)	15 (9.9)	48 (16.2)
		AG+GG	39 (50.0)	195 (51.4)	80 (53.0)	168 (56.8)

1 MM = malignant mesothelioma; SNP = single nucleotide polymorphism

TABLE 3.

Comparison of genotype frequencies distributions in all patients and in patients with pleural plaques versus controls

Protein (Gene)	Genotype	All asbestos diseases	P	OR (95% CI)_adj	P_adj	Pleural plaques	P	OR (95% CI)_adj	P_adj
Protein (Gene)	Genotype	OR (95% CI)	P	OR (95% CI)_adj	P_adj	OR (95% CI)	P	OR (95% CI)_adj	P_adj
PD-1 (PDCD1)	CC	Reference		Reference		reference	reference	reference	reference
rs2227982	CT+TT	0.80 (0.276-2.31)	0.679	0.93 (0.32-2.72)	0.889	0.88 (0.29-2.70)	0.83	0.93 (0.30-2.86)	0.91
PD-1 (PDCD1)	CC	Reference		Reference		reference	reference	reference	reference
rs2227981	CT	1.30 (0.77-2.20)	0.322	1.27 (0.75-2.16)	0.371	1.40 (0.81-2.44)	0.23	1.41 (0.81-2.44)	0.23
	TT	1.04 (0.54-2.02)	0.898	1.01 (0.52-1.97)	0.971	1.15 (0.57-2.31)	0.69	1.14 (0.67-2.29)	0.71
	CT+TT	1.22 (0.75-1.99)	0.416	1.19 (0.73-1.95)	0.482	1.33 (0.79-2.22)	0.28	1.32 (0.79-2.22)	0.29
PD-1 (PDCD1)	GG	Reference		Reference		reference	reference	reference	reference
rs10204525	GA	0.91 (0.51-1.64)	0.749	0.91 (0.50-1.64)	0.737	1.00 (0.54-1.86)	1.00	0.99 (0.53-1.85)	0.98
	AA	0.36 (0.74-1.72)	0.198	0.44 (0.90-2.13)	0.304	0.60 (0.12-3.05)	0.54	0.62 (0.12-3.16)	0.57
	GA+AA	0.84 (0.48-1.49)	0.554	0.85 (0.48-1.50)	0.572	0.95 (0.53-1.72)	0.87	0.95 (0.53-1.72)	0.87
PD-L1 (CD274)	GG	Reference		Reference		reference	reference	reference	reference
rs2297136	GA	0.86 (0.46-1.58)	0.614	0.78 (0.42-1.46)	0.443	0.82 (0.43-1.56)	0.54	0.80 (0.42-1.53)	0.50
	AA	0.99 (0.49-1.98)	0.967	0.90 (0.44-1.83)	0.771	1.1 (0.54-2.30)	0.78	1.08 (0.52-2.24)	0.85
	GA+AA	0.90 (0.5-1.61)	0.713	0.82 (0.45-1.49)	0.516	0.91 (0.49-1.68)	0.76	0.89 (0.48-1.65)	0.70
PD-L1 (CD274)	GG	Reference		Reference		reference	reference	reference	reference
rs4143815	GC	1.24 (0.76-2.02)	0.397	1.20 (0.73-1.97)	0.468	1.24 (0.74-2.08)	0.41	1.23 (0.73-2.06)	0.43
	CC	1.60 (0.70-3.70)	0.267	1.67 (0.72-3.87)	0.232	1.93 (0.82-4.56)	0.14	1.92 (0.81-4.55)	0.14
	GC+CC	1.30 (0.82-2.07)	0.266	1.29 (0.80-2.06)	0.298	1.37 (0.84-2.23)	0.21	1.36 (0.83-2.21)	0.22
PD-L1 (CD274)	AA	Reference		Reference		reference	reference	reference	reference
rs4742098	AG	1.23 (0.74-2.03)	0.421	1.21 (0.73-2.01)	0.446	1.24 (0.73-2.10)	0.43	1.23 (0.73-2.09)	0.44
	GG	1.01 (0.44-2.34)	0.978	1.00 (0.43-2.34)	0.993	1.30 (0.55-3.10)	0.56	1.29 (0.54-3.07)	0.57
	AG+GG	1.18 (0.74-1.90)	0.481	1.17 (0.73-1.87)	0.527	1.25 (0.76-2.05)	0.37	1.24 (0.76-2.04)	0.39
CTLA-4 (CTLA4)	AA	Reference		Reference		reference	reference	reference	reference
rs4553808	AG	0.74 (0.45-1.22)	0.238	0.72 (0.43-1.20)	0.210	0.72 (0.42-1.22)	0.23	0.71 (0.42-1.21)	0.21
	GG	0.34 (0.15-0.74)	0.007	0.32 (0.15-0.72)	0.006	0.28 (0.11-0.68)	0.01	0.28 (0.11-0.67)	0.01
	AG + GG	0.64 (0.40-1.02)	0.062	0.62 (0.39-1.00)	0.051	0.61 (0.37-1.00)	0.05	0.61 (0.37-1.00)	0.05
CTLA-4 (CTLA4)	CC	Reference		Reference		reference	reference	reference	reference
rs5742909	CT	0.92 (0.48-1.73)	0.791	0.97 (0.51-1.84)	0.919	0.87 (0.45-1.68)	0.67	0.86 (0.44-1.68)	0.66
	TT	0.54 (0.12-2.43)	0.418	0.48 (0.10-2.24)	0.353	0.36 (0.64-2.00)	0.24	0.37 (0.07-1.05)	0.26
	CT+TT	0.867 (0.48-1.58)	0.640	0.90 (0.49-1.65)	0.736	0.80 (0.43-1.50)	0.49	0.80 (0.42-1.50)	0.48
CTLA-4 (CTLA4)	AA	Reference		Reference		reference	reference	reference	reference
rs231775	AG	1.25 (7.6-2.08)	0.328	1.27 (0.76-2.11)	0.368	1.21 (0.71-2.05)	0.49	1.22 (0.72-2.07)	0.47
	GG	0.94 (0.47-1.91)	0.869	0.97 (0.48-1.98)	0.933	0.74 (0.35-1.58)	0.44	0.76 (0.36-1.62)	0.48
	AG+GG	1.17 (0.73-1.86)	0.517	1.18 (0.74-1.89)	0.485	1.08 (0.66-1.76)	0.77	1.09 (0.67-1.77)	0.74

1 adj = adjustment for age CI = confidence interval; MM = malignant mesothelioma; OR = odds ratio; SNP = single nucleotide polymorphism

TABLE 4.

Comparison of genotype frequencies distributions in patients with MM versus controls and versus patients with pleural plaques

Protein (Gene)	Genotype	MM versus controls	P	OR (95% CI)_adj	P_adj	MM versus pleural plaques	P	OR (95% CI)_αadj	P_adj
Protein (Gene)	Genotype	OR (95% CI)	P	OR (95% CI)_adj	P_adj	OR (95% CI)	P	OR (95% CI)_αadj	P_adj
PD-1 (PDCD1)	CC	reference	reference	reference	reference	reference	reference	reference	reference
rs2227982	CT+TT	0.65 (0.2-2.113)	0.47	0.98 (0.26-3.7)	0.98	0.92 (0.56-1.27)	0.60	0.88 (0.36-2.16)	0.78
PD-1 (PDCD1)	CC	reference	reference	reference	reference	reference	reference	reference	reference
rs2227981	CT	1.30 (0.74-2.28)	0.36	1.33 (0.71-2.50)	0.38	0.93 (0.65-1.3)	0.67	0.93 (0.63-1.38)	0.72
	TT	1.02 (5.0-2.0)	0.95	0.92 (0.41-2.05)	0.84	0.89 (0.57-1.40)	0.61	0.81 (0.49-1.36)	0.43
	CT+TT	1.22 (0.72-2.05)	0.467	1.20 (0.67-2.17)	0.54	0.92 (0.66-1.27)	0.60	0.9 (0.62-1.30)	0.58
PD-1 (PDCD1)	GG	reference	reference	reference	reference	reference	reference	reference	reference
rs10204525	GA	1.09 (0.56-2.11)	0.80	0.80 (0.39-1.64)	0.55	0.76 (0.51-1.14)	0.18	0.81 (0.52-1.26)	0.35
	AA	1.02 (0.48-2.19)	0.94	0.35 (0.03-4.30)	0.41	2.0 (0.02-1.66)	0.14	0.32 (0.03-2.92)	0.31
	GA+AA	0.69 (0.37-1.28)	0.23	0.76 (0.38-1.52)	0.44	0.72 (0.49-1.07)	0.10	0.78 (0.40-1.20)	0.26
PD-L1 (CD274)	GG	reference	reference	reference	reference	reference	reference	reference	reference
rs2297136	GA	1.09 (0.56-2.12)	0.80	1.16 (0.55-2.41)	0.70	1.34 (0.89-2.01)	0.16	1.31 (0.83-2.08)	0.25
	AA	1.03 (0.48-2.19)	0.94	1.00 (0.43-2.34)	1.0	0.92 (0.59-1.46)	0.74	0.78 (0.47-1.32)	0.36
	GA+AA	1.07 (0.57-2.02)	0.83	1.11 (0.55-2.25)	0.78	1.18 (0.80-1.74)	0.40	1.10 (0.711-1.71)	0.66
PD-L1 (CD274)	GG	reference	reference	reference	reference	reference	reference	reference	reference
rs4143815	GC	1.23 (0.73-2.08)	0.44	1.27 (0.71-2.28)	0.42	0.99 (0.72-1.37)	0.95	0.96 (0.67-1.38)	0.83
	CC	1.16 (0.47-2.87)	0.74	0.93 (0.35-2.48)	0.90	0.60 (0.36-1.01)	0.05	0.6 (0.34-1.06)	0.08
	GC+CC	1.22 (0.74-2.01)	0.44	1.20 (0.69-2.10)	0.51	0.89 (0.66-1.21)	0.46	0.87 (0.62-1.23)	0.43
PD-L1 (CD274)	AA	reference	reference	reference	reference	reference	reference	reference	reference
rs4742098	AG	1.17 (0.68-2.00)	0.58	1.14 (0.63-2.06)	0.67	0.94 (0.68-1.30)	0.71	0.92 (0.64-1.32)	0.65
	GG	0.77 (0.31-1.94)	0.58	0.58 (0.21-1.60)	0.29	0.59 (0.33-1.05)	0.07	0.53 (0.28-1.01)	0.56
	AG + GG	1.08 (0.65-1.79)	0.76	1.01 (0.58-1.77)	0.97	0.87 (0.64-1.17)	0.35	0.83 (0.59-1.13)	0.30
CTLA-4 (CTLA4)	AA	reference	reference	reference	reference	reference	reference	reference	reference
rs4553808	AG	0.72 (0.42-1.24)	0.24	0.61 (0.33-1.13)	0.11	1.00 (0.72-1.40)	0.99	0.88 (0.60-1.29)	0.50
	GG	0.38 (0.16-0.93)	0.03	0.40 (0.15-1.06)	0.06	1.38 (0.66-2.86)	0.39	1.24 (0.56-2.73)	0.60
	AG+GG	0.64 (0.39-1.06)	0.08	0.56 (0.32-0.98)	0.04	1.04 (0.76-1.43)	0.79	0.92 (0.65-1.32)	0.66
CTLA-4 (CTLA4)	CC	reference	reference	reference	reference	reference	reference	reference	reference
rs5742909	CT	0.95 (0.48-1.86)	0.87	1.03 (0.48-2.22)	0.94	1.01 (0.73.-1.63)	0.67	1.11 (0.71-1.75)	0.64
	TT	0.57 (0.11-3.02)	0.51	0.31 (0.05-1.86)	0.20	1.59 (0.42-6.00)	0.49	1.42 (0.32-6.27)	0.65
	CT+TT	0.90 (0.47-1.70)	0.74	0.90 (0.44-1.86)	0.78	1.12 (0.76-1.66)	0.56	1.13 (0.73-1.76)	0.58
CTLA-4 (CTLA4)	AA	reference	reference	reference	reference	reference	reference	reference	reference
rs231775	AG	1.31 (0.757-2.25)	0.34	1.36 (0.74-2.50)	0.32	1.08 (0.78-1.50)	0.64	1.11 (0.77-1.61)	0.58
	GG	1.33 (0.63-2.81)	0.46	1.76 (0.76-4.08)	0.19	1.79 (1.10-2.89)	0.02	2.1 (1.19-3.56)	0.01
	AG + GG	1.31 (0.80-2.16)	0.29	1.47 (0.84-2.57)	0.18	1.22 (0.90-1.66)	0.21	1.29 (0.91-1.81)	0.15

1 adj = adjustment for age; CI = confidence interval; MM = malignant mesothelioma; OR = odds ratio; SNP = single nucleotide polymorphism

TABLE 5.

Association of CTLA4 haplotypes with susceptibility for asbestos diseases

Haplotype	Predicted frequency in asbestos diseases	Predicted frequency in controls	OR (95% CI)	P	OR (95% CI)_adj	P_adj
ACA	0.460	0.369	Reference
ACG	0.328	0.320	0.84 (0.58-1.22)	0.359	0.84 (0.58-1.23)	0.379
GCA	0.106	0.183	0.49 (0.31-0.78)	0.003	0.46 (0.28-0.75)	0.002
GTA	0.101	0.120	0.68 (0.39-1.19)	0.181	0.71 (0.40-1.24)	0.222

1 adj = adjustment for age; CI = confidence interval; MM = malignant mesothelioma; OR = odds ratio; SNP = single nucleotide polymorphism

1 SNPs are listed from 5’ to 3’: rs4553808, rs5742909, rs231775

Articles in this issue

DOI: https://doi.org/10.2478/raon-2026-0035 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 271 - 281

Submitted on: Apr 9, 2026

Accepted on: Apr 23, 2026

Published on: Jun 26, 2026

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

asbestos,

malignant mesothelioma,

immune checkpoints,

single nucleotide polymorphism

Related subjects:

Medicine,

Clinical medicine,

Radiology

© 2026 Irma Zeljkovic, Katja Goricar, Tanja Blagus, Alenka Franko, Viljem Kovac, Vita Dolzan, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 60 (2026): Issue 2 (June 2026)