Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Volume 58 (2024): Issue 1 (March 2024)

By:

Ana Mervic, Katja Goricar, Tanja Blagus, Alenka Franko, Katarina Trebusak-Podkrajsek, Metoda Dodic Fikfak, Vita Dolzan and Viljem Kovac

Open Access

|Feb 2024

Figures & Tables

Relative telomere length in cases with pleural plaques (PP) and patients with malignant mesothelioma (MM).Alb = albumin gene product Tel = telomere product

Relative telomere length at different time points A, B and C.A = telomere length before first chemotherapy cycle: B = telomere length at third chemotherapy cycle; C = telomere length after completed chemotherapy or at disease progression

Kaplan Meier survival plot.Step = disease progression; cross = censored patient; AA = adenine-adenine; CA = cytosineadenine; CC = cytosine-cytosine; hTERT = telomerase reverse transcriptase

Association between telomere length and progression-free survival in patients with malignant mesothelioma (MM)

Telomere length	HR (95% CI)	P	HR (95% CI)_adj	P_adj
A	2.15 (0.69–6.68)	0.185	1.66 (0.50–5.47)	0.408
B	1.02 (0.28–3.76)	0.976	0.92 (0.22–3.76)	0.905
C	1.69 (0.46–6.16)	0.430	1.49 (0.40–5.48)	0.551
Comparison B vs. A	0.16 (0.03–1.01)	0.052	0.23 (0.03–1.67)	0.145
Comparison C vs. A	1.01 (0.25–4.18)	0.985	1.36 (0.31–5.92)	0.682
Comparison C vs. B	1.57 (0.26–9.58)	0.624	2.16 (0.31–14.83)	0.435

Association between telomere length and chemotherapy response rate in patients with malignant mesothelioma (MM)

Telomere length	Poor response Median (25–75%)	Good response Median (25–75%)	P
A	1.20 (1.01–1.37)	1.28 (1–1.39)	0.576
B	1.21 (1.05–1.37)	1.28 (1.13–1.35)	0.601
C	1.29 (1.07–1.37)	1.23 (1.02–1.34)	0.369
Comparison B vs. A	0.04 (−0.1 to 0.1)	−0.01 (−0.11 to 0.07)	0.317
Comparison C vs. A	0.01 (−0.09 to 0.22)	−0.04 (−0.16 to 0.15)	0.241
Comparison C vs. B	0.03 (−0.09 to 0.13)	−0.01 (−0.12 to 0.07)	0.353

Comparison of genotype frequencies in control group, cases with pleural plaques (PP) and patients with malignant mesothelioma (MM)

		Control group (N = 86)	Cases with PP (N = 386)	Patients with MM (N = 302)	P

SNP	Genotype	N (%)	N (%)	N (%)
rs2736098	CC	45 (56.3)	215 (56.3)	139 (46.8)	Padd = 0.018
	CT	28 (35.0)	133 (34.8)	140 (47.1)
	TT	7 (8.8)	34 (8.9)	18 (6.1)
	CT+TT	35 (43.8)	167 (43.7)	158 (53.2)	Pdom = 0.039
rs2736100	CC	17 (20.0)	103 (26.8)	93 (30.8)	Padd = 0.362
	CA	48 (56.5)	194 (50.4)	147 (48.7)
	AA	20 (23.5)	88 (22.9)	62 (20.5)
	CA+AA	68 (80.0)	282 (73.2)	209 (69.2)	Pdom = 0.127
rs10069690	CC	48 (63.2)	233 (61.0)	160 (54.6)	Padd = 0.107
	CT	26 (34.2)	131 (34.3)	107 (36.5)
	TT	2 (2.6)	18 (4.7)	26 (8.9)
	CT+TT	28 (36.8)	149 (39.0)	133 (45.4)	Pdom = 0.178

Characteristics of subjects included in the study

Characteristics	Category/unit	Total participants (N = 774)	Control group (N = 86)	Cases with PP (N = 386)	Patients with MM (N = 302)	P
Gender	Male, N (%)	555 (71.7)	63 (73.3)	269 (69.7)	223 (73.8)	0.467^a
Gender	Female, N (%)	219 (28.3)	23 (26.7)	117 (30.3)	79 (26.2)	0.467^a
Age	Years, median (25%–75%)	59.1 (51.1–67.5)	53.3 (48.1–59.5)	55.0 (48.8–62.7)	66.0 (59.0–73.0)	< 0.001^b
Smoking	No, N (%)	398 (52.0) [8]	47 (54.7)	189 (49.0)	162 (55.1)	0.254^a
Smoking	Yes, N (%)	368 (48.0)	39 (45.3)	197 (51.0)	132 (44.9)	0.254^a

Clinical characteristics of patients with malignant mesothelioma (MM) (N = 302)

Characteristics	Category	N (%)
Location [1]	Pleura	267 (88,7)
Location [1]	Peritoneum	34 (11,3)
Histology type	Epithelioid	227 (75,2)
	Biphasic	27 (8,9)
	Sarcomatoid	27 (8,9)
	Undifferentiated	21 (6,9)
Stage (pleural MM)	1	20 (7,5)
	2	65 (24,3)
	3	89 (33,3)
	4	93 (34,8)
ECOG performance status [1]	0	18 (6,0)
	1	154 (51,2)
	2	111 (36,9)
	3	18 (6,0)
Asbestos exposure [8]	No	79 (26,9)
Asbestos exposure [8]	Yes	215 (73,1)
Pain [29]	No	114 (41,8)
Pain [29]	Yes	159 (58,2)
Weight loss [34]	No	97 (36,2)
Weight loss [34]	Yes	171 (63,8)
CRP [mg/mL] [48]	Median (25%–75%)	22 (7–63,5)
Chemotherapy [21]	No chemotherapy	17 (6.1)
	Gemcitabine with cisplatin	161 (57.3)
	Pemetrexed with cisplatin	92 (31.6)
	Other	11 (3.9)
Chemotherapy response [46]	CR	10 (3.9)
	PR	73 (28.5)
	SD	128 (50.0)
	PD	45 (17.6)
Response rate	Poor response (SD+PD)	173 (67.6)
Response rate	Good response (PR+CR)	83 (32.4)

Telomere length in patients with malignant mesothelioma (MM) at different time points during chemotherapy

Time point	N	Median (25%–75%)	P	N shortens/N prolongs
A	79	1.23 (1.01–1.37)
B	66	1.23 (1.10–1.38)
C	66	1.27 (1.08–1.36)
Comparison B vs. A	66		0.480	28 shortens
Comparison B vs. A	66		0.480	38 prolongs
Comparison C vs. A	66		0.423	32 shortens
Comparison C vs. A	66		0.423	34 prolongs
Comparison C vs. B	53		0.733	26 shortens
Comparison C vs. B	53		0.733	27 prolongs

Association between selected polymorphism and chemotherapy response rate in patients with malignant mesothelioma (MM)

SNP	Genotype	Poor response N (%)	Good response N (%)	OR (95% CI)	P	OR (95% CI)_adj	P_adj
rs2736098	CC	81 (68.6)	37 (31.4)	Reference		Reference
	CT	76 (65.5)	40 (34.5)	1.15 (0.67–1.99)	0.611	1.20 (0.67–2.16)	0.542
	TT	11 (64.7)	6 (35.3)	1.19 (0.41–3.47)	0.745	1.27 (9.42–3.87)	0.671
	CT+TT	87 (65.4)	46 (34.6)	1.16 (0.68–1.96)	0.587	1.21 (0.69–2.14)	0.511
rs2736100	CC	53 (67.1)	26 (32.9)	Reference		Reference
	CA	89 (70.6)	37 (29.4)	0.85 (0.46–1.55)	0.592	0.85 (0.45–1.63)	0.625
	AA	31 (60.8)	20 (39.2)	1.32 (0.63–2.74)	0.463	1.16 (0.53–2.57)	0.709
	CA+AA	120 (67.8)	57 (32.2)	0.97 (0.55–1.70)	0.911	0.94 (0.51–1.71)	0.831
rs10069690	CC	94(72.9)	35 (27.1)	Reference		Reference
	CT	58 (59.8)	39 (40.2)	1.81 (1.03–3.17)	0.039	2.08 (1.13–3.84)	0.019
	TT	14 (66.7)	7 (33.3)	1.34 (0.50–3.60)	0.558	1.85 (0.64–5.31)	0.255
	CT+TT	72 (61.0)	46 (39.0)	1.72 (1.00–2.93)	0.048	2.04 (1.13–3.67)	0.017

Association between selected polymorphisms and progression–free survival in patients with malignant mesothelioma (MM)

SNP	Genotype	PFS Median (25%–75%)	HR (95% CI)	P	HR (95% CI)_adj	P_adj
rs2736098	CC	10.2 (6.5–18.9)	Reference		Reference
	CT	9.4 (6.1–14.5)	1.21 (0.93–1.57)	0.163	1.31 (0.98–1.76)	0.073
	TT	10.0 (6.6–14.2)	1.32 (0.79–2.20)	0.294	1.46 (0.82–2.59)	0.194
	CT+TT	9.7 (6.3–14.3)	1.22 (0.95–1.57)	0.127	1.33 (1.00–1.77)	0.051
rs2736100	CC	9.4 (5.9–13.4)	Reference		Reference
	CA	9.7 (6.4–14.9)	0.98 (0.74–1.30)	0.879	0.83 (0.60–1.14)	0.250
	AA	12.2 (7.1–20.1)	0.68 (0.47–0.98)	0.038	0.68 (0.45–1.03)	0.070
	CA+AA	10.2 (6.5–17.6)	0.87 (0.67–1.15)	0.328	0.78 (0.57–1.06)	0.113
rs10069690	CC	10.7 (6.3–16.5)	Reference		Reference
	CT	9.3 (6.1–15.0)	1.09 (0.83–1.42)	0.552	1.06 (0.79–1.43)	0.699
	TT	11.8 (7.3–13.4)	0.85 (0.52–1.38)	0.502	0.81 (0.48–1.38)	0.443
	CT+TT	9.4 (6.6–15.0)	1.04 (0.80–1.34)	0.791	1.01 (0.76–1.33)	0.963

Association between selected polymorphisms and overall survival in patients with malignant mesothelioma (MM)

SNP	Genotype	OS Median (25%–75%)	HR (95% CI)	P	HR (95% CI)_adj	P_adj
rs2736098	CC	18.2 (10.1–28.6)	Reference		Reference
	CT	19.3 (9.6–31.4)	1.01 (0.76–1.35)	0.944	1.02 (0.75–1.39)	0.899
	TT	24.4 (22.0–31.1)	0.84 (0.46–1.54)	0.573	0.94 (0.48–1.83)	0.859
	CT+TT	20.3 (9.9–31.2)	0.99 (0.75–1.31)	0.924	1.01 (0.75–1.36)	0.945
rs2736100	CC	17.5 (11.6–28.1)	Reference		Reference
	CA	19.3 (10.7–32.5)	0.87 (0.64–1.20)	0.404	0.88 (0.62–1.24)	0.460
	AA	20.6 (9.6–31.4)	0.79 (0.53–1.17)	0.229	0.86 (0.56–1.31)	0.478
	CA+AA	19.5 (10.0–32.5)	0.85 (0.63–1.14)	0.270	0.87 (0.63–1.21)	0.410
rs10069690	CC	20.3 (9.6–31.4)	Reference		Reference
	CT	19.3 (11.1–25.9)	1.09 (0.81–1.47)	0.578	1.13 (0.82–1.55)	0.455
	TT	16.0 (13.1–29.0)	1.01 (0.60–1.72)	0.958	0.74 (0.41–1.35)	0.321
	CT+TT	18.5 (11.4–29.0)	1.08 (0.81–1.43)	0.619	1.04 (0.77–1.41)	0.780

Association between selected polymorphisms and the risk of developing malignant mesothelioma (MM): comparison of patients with MM and other participants (control group and cases with pleural plaques [PP])

		Patients with MM	Others

SNP	Genotype	N (%)	N (%)	OR (95% CI)	P	OR (95% CI)_adj	P_adj
rs2736098	CC	139 (46.8)	260 (56.3)	Reference		Reference
	CT	140 (47.1)	161 (34.8)	1.63 (1.20–2.21)	0.002	1.49 (1.06–2.10)	0.023
	TT	18 (6.1)	41 (8.9)	0.82 (0.46–1.48)	0.514	0.78 (0.40–1.54)	0.470
	CT+TT	158 (53.2)	202 (43.7)	1.46 (1.09–1.96)	0.011	1.36 (0.98–1.88)	0.070
rs2736100	CC	93 (30.8)	120 (56.3)	Reference		Reference
	CA	147 (48.7)	242 (51.5)	0.78 (0.56–1.10)	0.160	0.71 (0.48–1.04)	0.076
	AA	62 (20.5)	108 (23.0)	0.74 (0.49–1.12)	0.155	0.56 (0.35–0.90)	0.017
	CA+AA	209 (69.2)	350 (74.5)	0.77 (0.56–1.06)	0.111	0.66 (0.46–0.95)	0.026
rs10069690	CC	160 (54.6)	281 (61.4)	Reference		Reference
	CT	107 (36.5)	157 (34.3)	1.20 (0.88–1.64)	0.261	1.41 (0.99–2.01)	0.058
	TT	26 (8.9)	20 (4.4)	2.28 (1.24–4.22)	0.008	2.22 (1.10–4.48)	0.026
	CT+TT	133 (45.4)	177 (38.6)	1.32 (0.98–1.78)	0.067	1.52 (1.08–2.12)	0.017

Association between selected polymorphisms and risk of developing malignant mesothelioma (MM): comparison of patients with MM and cases with pleural plaques (PP)

SNP	Genotype	OR (95% CI)	P	OR (95% CI)_adj	P_adj
rs2736098	CC	Reference		Reference
	CT	1.63 (1.18–2.24)	0.003	1.52 (1.06–2.16)	0.022
	TT	0.82 (0.45–1.51)	0.521	0.76 (0.38–1.53)	0.445
	CT+TT	1.46 (1.08–1.99)	0.014	1.37 (0.98–1.93)	0.069
rs2736100	CC	Reference		Reference
	CA	0.84 (0.59–1.19)	0.330	0.77 (0.52–1.15)	0.196
	AA	0.78 (0.51–1.20)	0.257	0.58 (0.36–0.94)	0.028
	CA+AA	0.82 (0.59–1.15)	0.245	0.71 (0.48–1.03)	0.070
rs10069690	CC	Reference		Reference
	CT	1.19 (0.86–1.65)	0.296	1.39 (0.96–2.01)	0.078
	TT	2.10 (1.12–3.96)	0.021	2.11 (1.02–4.34)	0.043
	CT+TT	1.30 (0.96–1.78)	0.096	1.48 (1.05–2.10)	0.027

DOI: https://doi.org/10.2478/raon-2024-0009 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 87 - 98

Submitted on: Aug 25, 2023

Accepted on: Sep 13, 2023

Published on: Feb 21, 2024

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 times per year

Keywords:

malignant mesothelioma,

Related subjects:

Haematology, oncology,

Radiology

© 2024 Ana Mervic, Katja Goricar, Tanja Blagus, Alenka Franko, Katarina Trebusak-Podkrajsek, Metoda Dodic Fikfak, Vita Dolzan, Viljem Kovac, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

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Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

Figures & Tables

FIGURE 1.

FIGURE 2.

FIGURE 3.

Association between telomere length and progression-free survival in patients with malignant mesothelioma (MM)

Association between telomere length and chemotherapy response rate in patients with malignant mesothelioma (MM)

Comparison of genotype frequencies in control group, cases with pleural plaques (PP) and patients with malignant mesothelioma (MM)

Characteristics of subjects included in the study

Clinical characteristics of patients with malignant mesothelioma (MM) (N = 302)

Telomere length in patients with malignant mesothelioma (MM) at different time points during chemotherapy

Association between selected polymorphism and chemotherapy response rate in patients with malignant mesothelioma (MM)

Association between selected polymorphisms and progression–free survival in patients with malignant mesothelioma (MM)

Association between selected polymorphisms and overall survival in patients with malignant mesothelioma (MM)

Association between selected polymorphisms and the risk of developing malignant mesothelioma (MM): comparison of patients with MM and other participants (control group and cases with pleural plaques [PP])

Association between selected polymorphisms and risk of developing malignant mesothelioma (MM): comparison of patients with MM and cases with pleural plaques (PP)

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