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

Our plain-English summary of Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases, by A. Mervic, K. Goricar, T. Blagus, et al (Radiology and Oncology, 2024).

The study

• Authors: A. Mervic, K. Goricar, T. Blagus, A. Franko, K. Trebusak-Podkrajsek, M.D. Fikfak, V. Dolzan, V. Kovac
• Journal: Radiology and Oncology
• Published: 2024;58(1):87-98
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2024 Ana Mervic et al., published by Sciendo.

In plain English

This Slovenian study asked whether telomere length in white blood cells (telomeres are protective caps on chromosomes) and three variants of the hTERT gene were linked to asbestos-related disease and to how malignant mesothelioma (MM) responded to chemotherapy. It combined a retrospective case-control study of 302 MM patients, 386 people with pleural plaques and 86 controls without asbestos-related disease with repeated telomere measurements in MM patients during chemotherapy. The plaque cases and controls had been occupationally exposed to asbestos at the Salonit Anhovo factory. MM patients had shorter telomeres than plaque cases (median relative length 1.23 versus 1.43). After adjustment for age, some rs2736098 and rs10069690 genotypes were associated with higher odds of MM, and rs2736100 genotypes with lower odds. Telomere length was not associated with chemotherapy response or progression. The rs10069690 T variant was associated with better chemotherapy response. The rs2736100 AA genotype was associated with longer progression-free survival, but not after adjustment. No variant was linked to overall survival. The authors concluded these markers have a limited role as biomarkers for asbestos-related disease risk. They noted a limited number of participants.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Two retrospective studies: a case-control study (MM patients, pleural plaque cases, controls) and a longitudinal observational study of telomere length in MM patients before, during and after chemotherapy
• Who was studied: 302 patients with malignant mesothelioma (267 pleural, 34 peritoneal) treated at the Institute of Oncology Ljubljana from 2008 to 2018. 386 cases with pleural plaques and 86 controls without asbestos-related disease, presented before the Slovenian State Board for the Recognition of Occupational Asbestos Diseases between January 1999 and December 2003. 94 MM patients had blood samples from at least two time points during chemotherapy (211 samples).
• Exposure: Occupational asbestos exposure at the Salonit Anhovo factory, Slovenia, for the plaque cases and controls. Exposure data for MM patients came from earlier studies and medical records. Among subjects with known exposure, 52.7% of MM patients had medium or high exposure, compared with 28.5% of plaque cases and 24.4% of controls. Fiber types are not specified. The markers studied were leukocyte telomere length and the hTERT polymorphisms rs10069690, rs2736100 and rs2736098.
• Main results:
  • MM patients had a shorter median relative telomere length, 1.23 (1.01 to 1.37), than cases with pleural plaques, 1.43 (1.32 to 1.56). The difference was p less than 0.001 and remained significant after adjustment for age.
  • Among MM patients, older patients had longer telomeres (Spearman's rho = 0.370; p less than 0.001).
  • MM patients compared with all other subjects (controls plus plaque cases): the rs2736098 CT genotype was associated with higher odds of MM, age-adjusted OR 1.49 (95% CI 1.06 to 2.10), p = 0.023.
  • MM patients compared with all other subjects: rs2736100 genotypes were associated with lower odds of MM after age adjustment. AA: OR 0.56 (95% CI 0.35 to 0.90), p = 0.017. CA+AA: OR 0.66 (0.46 to 0.95), p = 0.026.
  • MM patients compared with all other subjects: the rs10069690 TT genotype was associated with higher odds of MM, OR 2.28 (95% CI 1.24 to 4.22), p = 0.008. After age adjustment, CT+TT had OR 1.52 (1.08 to 2.12), p = 0.017.
  • In MM patients, telomere length and its changes during chemotherapy were not significantly associated with chemotherapy response (p greater than 0.05).
  • In MM patients, carriers of the rs10069690 T allele had better chemotherapy response. The unadjusted CT OR is 1.81 (1.03 to 3.17) in Table 8. Adjusted ORs were 2.08 (1.13 to 3.84) for CT, p = 0.019, and 2.04 (1.13 to 3.67) for CT+TT, p = 0.017.
  • Median follow-up was 41.7 months. Median progression-free survival was 10.0 months and median overall survival was 19.3 months.
  • In MM patients, the rs2736100 AA genotype was associated with longer progression-free survival than CC (HR 0.68; 95% CI 0.47 to 0.98; p = 0.038). In the adjusted analysis in Table 10 the HR was 0.68 (0.45 to 1.03), p = 0.070, which was not statistically significant.
  • Telomere length and its changes were not associated with progression-free survival, including after adjustment for CRP (all p greater than 0.05).
  • None of the three polymorphisms was associated with overall survival in MM patients.
• The authors' conclusion: The authors concluded that telomere length and hTERT polymorphisms have a limited role as biomarkers for the risk of developing asbestos-related diseases. Telomere length was not shown to be a biomarker of chemotherapy response. With cautious interpretation, hTERT polymorphisms may be biomarkers of chemotherapy outcome and of the risk of MM progression. Further validation in independent cohorts is needed.
• Limitations the authors state:
  • The findings on telomere length and chemotherapy response are based on a limited number of participants, and studies in MM patients are lacking.
  • Further investigation is needed to determine whether the age-adjusted association of rs2736100 with lower MM risk is coincidental.
  • The associations need validation in independent patient cohorts.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Asbestos Exposure, Chemotherapy, Malignant Mesothelioma, Case-Control Study, Pleural Plaques, Disease Progression.

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