Abstract C19: Prospective association between blood leukocyte telomere length and cancer incidence and mortality

Abstract

Abstract Background and Objective: Telomeres play a critical role in maintaining the structural integrity of chromosomes. Short telomeres may lead to chromosomal instability and increase cancer risk and related death. In this longitudinal study we examined prospective associations between blood leukocyte telomere length (TL) and cancer incidence and mortality. Methods: Our study population included a total of 791 participants in the prospective Normative Aging Study (NAS), a 1963-established study devoted to determining the health effects of aging. Between January 1999 and December 2012, the participants underwent blood drawing during the NAS visits every 3-5 years. We examined leukocyte TL using quantitative real-time PCR on blood samples collected at each NAS visit, including 1-4 examinations before cancer diagnosis. We used mixed models and Cox models to evaluate the association between TL with cancer incidence and mortality individually. Both models were adjusted for age, race, body mass index, education, and smoking status. Results: In 579 participants free of baseline cancers, telomeres were significantly shorter in association with aging (P < 0.001) and lower levels of education (P = 0.02). 137(23.7%) new cancer cases (47 prostate, 15 gastrointestinal, and 75 other cancers) occurred throughout the 14-year follow-up. Shorter TL was associated with higher incidence of all cancers combined (OR=1.54, 95%CI 1.02-2.33, P=0.04). Totally, 75 (9.5%) deaths occurred due to cancers (12 prostate, 18 gastrointestinal, 45 other cancers). Subjects with shorter TL (less than median) had increased mortality from all cancer combined (HR= 1.68, 95%CI 0.99-2.87, P=0.05). Relative to subjects in the fourth quartile (longest) of TL, subjects in the first quartile (shortest) had almost twice mortality risk from all cancer combined (HR= 1.90, 95% CI 0.92-3.93, P-trend=0.02). For the cancer subgroups, subjects with shorter TL (less than median) had increased mortality from other cancers (mostly lung and blood cancers)(HR= 2.01, 95%CI 1.07-3.75, P=0.03). Conclusion: Shorter TL is associated with higher risk of cancer incidence and cancer mortality independent of age, race, body mass index, education, and smoking. More studies are needed to determine the predictive value of blood leukocyte TL in specific cancers, as well as their underlying mechanisms. Citation Format: Tao Gao, Junjie Chu, Yinan Zheng, Xiao Zhang, Andrea A. Baccarelli, Joel Schwartz, Lifang Hou. Prospective association between blood leukocyte telomere length and cancer incidence and mortality. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C19.