<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Background</h3>
<p>Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and <italic>hTERT</italic> genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).</p>
</sec>
<sec><h3>Subjects and methods</h3>
<p>We conducted two retrospective studies. In the first study, a case-control study, telomere length and <italic>hTERT</italic> polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype <italic>hTERT</italic> rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.</p>
</sec>
<sec><h3>Results</h3>
<p>Patients with MM had shorter telomere length than subjects with pleural plaques (p &lt; 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (p<sub>adj</sub> = 0.023; p<sub>adj</sub> = 0.026 and p<sub>adj</sub> = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (p<sub>adj</sub> = 0.017, and p<sub>adj</sub> = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (p<sub>adj</sub> = 0.019; p<sub>adj</sub> = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).</p>
</sec>
<sec><h3>Conclusions</h3>
<p>Shorter telomere length and <italic>hTERT</italic> polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.</p>
</sec>
</abstract>

Background
Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).

Subjects and methods
We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.

Results
Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).

Conclusions
Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.

Telomere length and <italic>TERT</italic> polymorphisms as biomarkers in asbestos-related diseases

Institute of Biochemistry and Molecular Genetics, Faculty of Medicine

Clinical Institute of Occupational Medicine

Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital

Radiology and Oncology

This work is licensed under the Creative Commons Attribution 4.0 International License.

Telomere length and  polymorphisms as biomarkers in asbestos-related diseases

Background
Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).

Subjects and methods
We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.

Results
Patients with MM had shorter telomere length than subjects with pleural plaques (p  0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).

Conclusions
Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.

Background
Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in...

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

Article Category: Research Article

Publié en ligne: 21 févr. 2024

Pages: 87 - 98

Reçu: 25 août 2023

Accepté: 13 sept. 2023

DOI: https://doi.org/10.2478/raon-2024-0009

Mots clés
malignant mesothelioma, asbestos, telomere length, polymorphisms

© 2024 Ana Mervic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

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

Article Category: Research Article

Publié en ligne: 21 févr. 2024

Pages: 87 - 98

Reçu: 25 août 2023

Accepté: 13 sept. 2023

DOI: https://doi.org/10.2478/raon-2024-0009

Mots clésmalignant mesothelioma, asbestos, telomere length, polymorphisms

© 2024 Ana Mervic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Mots clés
malignant mesothelioma, asbestos, telomere length, polymorphisms