Open Access

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

Ana Mervic
Ana Mervic
, 
Katja Goricar
Katja Goricar
, 
Tanja Blagus
Tanja Blagus
, 
Alenka Franko
Alenka Franko
, 
Katarina Trebusak-Podkrajsek
Katarina Trebusak-Podkrajsek
, 
Metoda Dodic Fikfak
Metoda Dodic Fikfak
, 
Vita Dolzan
Vita Dolzan
 and 
Viljem Kovac
Viljem Kovac
   | Feb 21, 2024
Radiology and Oncology's Cover Image
About this article
Previous Article
Next Article
Cite
Article Category: Research Article
Published Online: Feb 21, 2024
Page range: 87 - 98
Received: Aug 25, 2023
Accepted: Sep 13, 2023
DOI: https://doi.org/10.2478/raon-2024-0009
Keywords
© 2024 Ana Mervic et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

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.
eISSN:
1581-3207
Language:
English
Publication timeframe:
4 times per year
Journal Subjects:
Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology, Radiology
Journal RSS Feed