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.


RESULTS
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).


CONCLUSIONS
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.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA ; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Olson Pavilion 8350, Chicago, IL 60611, USA.
Lifang
L
Hou
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA ; Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois-Chicago, 1603 W. Taylor St., Chicago, IL 60613, USA.
Brian Thomas
BT
Joyce
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
Tao
T
Gao
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA ; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Olson Pavilion 8350, Chicago, IL 60611, USA.
Lei
L
Liu
Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, 633 N. St. Clair St., Chicago, IL 60611, USA.
Yinan
Y
Zheng
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Olson Pavilion 8350, Chicago, IL 60611, USA ; Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, 633 N. St. Clair St., Chicago, IL 60611, USA.
Frank J
FJ
Penedo
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Rm E310, Evanston, IL 60208, USA.
Siran
S
Liu
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
Wei
W
Zhang
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Olson Pavilion 8350, Chicago, IL 60611, USA ; Department of Medicine, Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, 251 E. Huron St., Suite 3-150, Chicago, IL 60611, USA.
Raymond
R
Bergan
Vanderbilt University Medical Center, 2525 West End Ave, Suite 319, Nashville, TN 37203, USA.
Qi
Q
Dai
VA Normative Aging Study, VA Boston Healthcare System, 150 South Huntington Ave, Boston, MA 02130, USA ; Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Pantel
P
Vokonas
Molecular Epidemiology and Environmental Epigenetics Laboratory, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, San Barnaba 8, 20122 Milan, Italy.
Mirjam
M
Hoxha
Department of Environmental Health, Harvard School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA.
Joel
J
Schwartz
Department of Environmental Health, Harvard School of Public Health, 655 Huntington Ave, Boston, MA 02115, USA.
Andrea
A
Baccarelli
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000503:physiopathology*; D011446:Prospective Studies; D016615:Telomere / Q000502:physiology*; D059505:Telomere Homeostasis / Q000502:physiology*; D059506:Telomere Shortening / Q000502:physiology*
D014408:Biomarkers, Tumor
Cancer incidence; Longitudinal study; Telomere