Leucocyte Telomere Length and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Studies

Simple Summary Telomere length (TL) may influence the carcinogenesis process. Short telomeres lead to genomic instability, which is an important event in tumor initiation, while long telomeres may promote cell division and immortality influencing tumor promotion/progression. Despite the numerous observational epidemiological studies available, the association between TL in leukocytes (LTL) and lung cancer risk is currently still uncertain. Therefore, we conducted this systematic review and meta-analysis of prospective studies to summarize the evidence and derive a more accurate estimate of the effect of LTL on lung cancer occurrence. Longer LTL could be a marker to identify subjects at high risk of developing lung cancer. This may help to focus secondary prevention (screening) on specific groups of subjects.Abstract Although numerous epidemiological studies are available, the relationship between leukocyte telomere length (LTL) and lung cancer risk is still controversial. This systematic review and meta-analysis, performed according to the PRISMA statement and MOOSE guidelines, aims to summarize the evidence and calculate the risk of lung cancer associated with LTL. The literature search was performed on PubMed, Web of Science, and Scopus databases through May 2024. A random-effects model was used to calculate the pooled risk. Heterogeneity was assessed using I2 and Cochran's Q statistic. Begg's and Egger's tests were used to detect publication bias. Based on 8055 lung cancer cases and 854,653 controls (nine prospective studies), longer LTL was associated with a significant 42% increment in all types of lung cancer risk (OR 1.42, 95% CI 1.24-1.63). The effect was even more evident for adenocarcinomas (OR 1.98, 95% CI 1.69-2.31), while no association was observed for squamous cell carcinoma (OR 0.87, 95% CI 0.72-1.06). Significantly, no association was found for current smokers (OR 1.08, 95% CI 0.90-1.30), while it remained high for both never-smokers (OR 1.92, 95% CI 1.62-2.28) and former smokers (OR 1.34, 95% CI 1.11-1.62). No significant publication bias was evidenced. Longer LTL is associated with an increment in lung cancer risk particularly in never-smoker subjects.