Association of Telomere Length With Risk of Disease and Mortality
Menée sur la période 2006-2010 à partir de données de la "UK Biobank" portant sur 472 432 personnes (54 % de femmes ; âge moyen : 57 ans ; durée moyenne de suivi : 12 ans), cette étude analyse l'association entre la longueur des télomères des leucocytes et le risque de développer certaines maladies comme le cancer, ainsi que la mortalité globale et spécifique
Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders.To determine the association between LTL and overall as well as disease-specific mortality and morbidity.This multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021.Hazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity.This study included a total of 472 432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR, 1.08; 95% CI, 1.07-1.09), cardiovascular (HR, 1.09; 95% CI, 1.06-1.12), respiratory (HR, 1.40; 95% CI, 1.34-1.45), digestive (HR, 1.26; 95% CI, 1.19-1.33), musculoskeletal (HR, 1.51; 95% CI, 1.35-1.92), and COVID-19 (HR, 1.15; 95% CI, 1.07-1.23) mortality, but not cancer-related mortality. A total of 214 disorders were significantly overrepresented and 37 underrepresented in participants with shorter LTL. Respiratory (11%), digestive/liver-related (14%), circulatory (18%), and musculoskeletal conditions (6%), together with infections (5%), accounted for most positive associations, whereas (benign) neoplasms and endocrinologic/metabolic disorders were the most underrepresented entities. Malignant tumors, esophageal cancer, and lymphoid and myeloid leukemia were significantly more common in participants with shorter LTL, whereas brain cancer and melanoma were less prevalent. While smoking and alcohol consumption were associated with shorter LTL, additional adjustment for both factors, as well as cognitive function/major comorbid conditions, did not significantly alter the results.This cohort study found that shorter LTL was associated with a small risk increase of overall mortality, but a higher risk of mortality was associated with specific organs and diseases.
JAMA Internal Medicine , résumé, 2021