Abstract 4593: Telomere length measured prior to lung cancer diagnosis and survival by histologic type
Authors: Doherty Jennifer A. , Houck John , Barnett Matt J. , Tapsoba Jean DD , Julianto Liberto , Thornquist Mark D. , Wang Ching-Yun , Chen Chu , Goodman Gary E. 
Published: August 2015

Short telomere length is thought to be a marker of increased cumulative cellular aging, and has been reported to be associated with poor survival from a variety of cancer types, including lung cancer. We examined associations between telomere length and overall survival for the major lung cancer histologic types in very heavy smokers from the Beta Carotene and Retinol Trial (CARET). CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial of daily β-carotene and retinyl palmitate in smokers with ≥20 pack-years, and smokers who were occupationally exposed to asbestos. Individuals who provided blood and were later diagnosed with lung cancer were included in the study. Telomere length was successfully measured on average 5 years prior to diagnosis for 711 lung cancer cases, of whom 648 died during follow up (median survival 1.5 years). Telomere length was negatively associated with increasing age (p&lt;0.0001), but was not associated with any aspect of smoking exposure. Hazard ratios (HRs) for decreasing quintiles of telomere length were calculated using Cox proportional hazards regression. After controlling for age at blood draw, sex, race, enrollment year, placebo/active intervention, asbestos exposure, current/former smoking and time since quit, pack years, average number of cigarettes per day, tumor stage and histologic type, shorter telomere length was associated with decreased survival. Overall, HRs and 95% confidence intervals (CIs) for decreasing quintiles of telomere length and risk of death were: 1.0 (reference), 1.40 (1.08-1.83), 1.21 (0.94-1.54), 1.46 (1.13-1.89), and 1.37 (1.05-1.78), p trend = 0.02. Associations were considerably stronger for small cell carcinoma (HRs (95% CIs): 1.0, 3.39 (1.45-7.94), 1.88 (0.95-3.72), 3.62 (1.68-7.81), 2.91 (1.37-6.22), p = 0.01) and adenocarcinoma (HRs (95% CIs): 1.0, 1.00 (0.57-1.78), 1.23 (0.72-2.11), 1.78 (1.02-3.10), 1.77 (1.03-3.05), p = 0.01), than for squamous cell carcinoma (HRs (95% CIs): 1.0, 2.58 (1.29-5.15), 0.97 (0.52-1.82), 1.24 (0.65-2.34), 1.17 (0.58-2.35), p = 0.99), and stronger for stage III/IV disease (HRs (95% CIs): 1.0, 1.55 (1.07-2.23), 1.21 (0.88-1.67), 1.74 (1.23-2.47), 1.48 (1.05-2.08), p = 0.02) than for early stage disease (HRs (95% CIs): 1.0, 1.05 (0.55-2.03), 0.68 (0.37-1.26), 1.11 (0.60-2.05), 1.06 (0.53-2.09), p = 0.88). As well, short telomere length was associated with particularly poor survival among individuals &lt;65 years at diagnosis (HRs (95% CIs): 1.0, 2.37 (1.35-4.15), 1.99 (1.16-3.44), 2.31 (1.21-4.40), 2.93 (1.61-5.33), p = 0.0007) but not among individuals ages 65 and older (HRs (95% CIs): 1.0, 1.15 (0.85-1.56), 0.98 (0.74-1.30), 1.26 (0.94-1.68), 1.09 (0.81-1.47), p = 0.39). Short telomere length measured prior to diagnosis may be a marker for poor survival after a diagnosis of lung cancer, particularly for small cell carcinoma and adenocarcinoma, and for individuals diagnosed before age 65.

Citation Format: Jennifer A. Doherty, John Houck, Matt J. Barnett, Jean DD Tapsoba, Liberto Julianto, Mark D. Thornquist, Ching-Yun Wang, Chu Chen, Gary E. Goodman. Telomere length measured prior to lung cancer diagnosis and survival by histologic type. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4593. doi:10.1158/1538-7445.AM2015-4593