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

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 (p_difference=0.017); all participants had similar age-adjusted BTL 8-14years 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 ≤4years 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.