Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort

• Main Authors: Lifang Hou, Brian Thomas Joyce, Tao Gao, Lei Liu, Yinan Zheng, Frank J. Penedo, Siran Liu, Wei Zhang, Raymond Bergan, Qi Dai, Pantel Vokonas, Mirjam Hoxha, Joel Schwartz, Andrea Baccarelli
• Format: Article
• Language: English
• Published: Elsevier 2015-06-01
• Series: EBioMedicine
• Subjects: Telomere; Longitudinal study; Cancer incidence
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352396415001024

Background: Accelerated telomere shortening may cause cancer via chromosomal instability, making it a potentially useful biomarker. However, publications on blood telomere length (BTL) and cancer are inconsistent. We prospectively examined BTL measures over time and cancer incidence. Methods: We included 792 Normative Aging Study participants with 1–4 BTL measurements from 1999 to 2012. We used linear mixed-effects models to examine BTL attrition by cancer status (relative to increasing age and decreasing years pre-diagnosis), Cox models for time-dependent associations, and logistic regression for cancer incidence stratified by years between BTL measurement and diagnosis. Findings: Age-related BTL attrition was faster in cancer cases pre-diagnosis than in cancer-free participants (pdifference = 0.017); all participants had similar age-adjusted BTL 8–14 years pre-diagnosis, followed by decelerated attrition in cancer cases resulting in longer BTL three (p = 0.003) and four (p = 0.012) years pre-diagnosis. Longer time-dependent BTL was associated with prostate cancer (HR = 1.79, p = 0.03), and longer BTL measured ≤4 years pre-diagnosis with any (OR = 3.27, p < 0.001) and prostate cancers (OR = 6.87, p < 0.001). Interpretation: Age-related BTL attrition was faster in cancer cases but their age-adjusted BTL attrition began decelerating as diagnosis approached. This may explain prior inconsistencies and help develop BTL as a cancer detection biomarker.