Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers

Author:

Córdoba-Lanús Elizabeth123ORCID,Montuenga Luis M.4567ORCID,Domínguez-de-Barros Angélica2ORCID,Oliva Alexis28ORCID,Mayato Delia9,Remírez-Sanz Ana5,Gonzalvo Francisca9,Celli Bartolomé10,Zulueta Javier J.11,Casanova Ciro1912ORCID

Affiliation:

1. Department of Internal Medicine, Dermatology and Psychiatry, University of La Laguna, 38296 San Cristóbal de La Laguna, Spain

2. Instituto de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), 38029 San Cristóbal de La Laguna, Spain

3. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain

4. Department of Pathology, Anatomy and Physiology, School of Medicine and Sciences, University of Navarra, 31008 Pamplona, Spain

5. CIMA—Centro de Investigación Médica Aplicada, University of Navarra, 31008 Pamplona, Spain

6. Navarra Institute for Health Research (IdISNA), 31008 Pamplona, Spain

7. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain

8. Department of Pharmaceutical Technology, University of La Laguna, 38296 San Cristóbal de La Laguna, Spain

9. Pulmonary Division, Research Unit, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain

10. Pulmonary Critical Care Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

11. Pulmonary, Critical Care and Sleep Medicine Division, Mount Sinai Morningside Hospital, Icahn School of Medicine, New York, NY 10025, USA

12. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain

Abstract

Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length (p < 0.001) and increased serum 8-OHdG levels (p = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients.

Funder

Instituto de Salud Carlos III

European Regional Development Fund

Spanish Respiratory Society, SEPAR

Menarini Laboratory S.A.

Cabildo de Tenerife, Tenerife 2030, FDCAN, MEDI

Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas CIBERINFEC

Instituto de Salud Carlos III, Spain

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

Reference54 articles.

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3. GOLD (2023, November 03). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease-2022 Report. Available online: https://goldcopd.org/wp-content/uploads/2021/11/GOLD-REPORT-2022-v1.0-12Nov2021_WMV.pdf.

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