Telomere Length and Lung Cancer Mortality among Heavy Smokers

Background: Accumulating evidence suggests that short telomere length is associated with increased overall mortality, but the relationship with cancer mortality is less clear. We examined whether telomere length (global, and chromosome arm 5p- and 13q-specific) is associated with lung cancer mortality among cases from the β-Carotene and Retinol Efficacy Trial of heavy smokers.Methods: Telomere length was measured on average 6 years before diagnosis for 788 lung cancer cases. Adjusted Cox proportional hazards models of all-cause and lung cancer-specific mortality were assessed for lung cancer overall and by histotype.Results: Short telomere length was associated with increased mortality for small cell lung cancer (SCLC), particularly stage III/IV SCLC [HR and 95% confidence interval for shortest vs. longest telomere length tertile: 3.32 (1.78-6.21)]. Associations were strongest for those randomized to the active intervention and when telomere length was measured ≤5 years before diagnosis. All-cause mortality patterns were similar. Short chromosome 5p telomere length was suggestively associated with lung cancer mortality, but there was no association with chromosome 13q telomere length.Conclusions: Our large prospective study suggests that among heavy smokers who developed lung cancer, short prediagnosis telomere length is associated with increased risk of death from SCLC.Impact: This is the first study to examine telomere length and mortality in lung cancer cases by histotype. If the association between short telomere length and SCLC mortality is replicated, elucidation of mechanisms through which telomere length influences survival for this highly aggressive cancer may inform more effective use of telomere-targeted therapeutics. Cancer Epidemiol Biomarkers Prev; 27(7); 829-37. ©2018 AACR.