Change in Peripheral Blood Leukocyte Telomere Length and Mortality in Breast Cancer Survivors.
Author: Duggan C1, Risques R, Alfano C, Prunkard D, Imayama I, Holte S, Baumgartner K, Baumgartner R, Bernstein L, Ballard-Barbash R, Rabinovitch P, McTiernan A.
Affiliation:
1Affiliations of authors: Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (CD, II, SH, AM); Department of Pathology (RR, DP, PR), Department of Epidemiology, School of Public Health (AM), and Department of Medicine, School of Medicine, University of Washington, Seattle, WA (RR, DP, PR, AM); Office of Cancer Survivorship (CA) and Applied Research Program (RB-B), National Cancer Institute/National Institutes of Health, Bethesda, MD; Department of Epidemiology & Population Health, University of Louisville, Louisville, KY (KB, RB); Department of Cancer Etiology, City of Hope National Medical Center, Duarte, CA (LB).
Conference/Journal: J Natl Cancer Inst.
Date published: 2014 Mar 13
Other:
Word Count: 267
BACKGROUND:
Progressive telomere shortening with cell division is a hallmark of aging. Short telomeres are associated with increased cancer risk, but there are conflicting reports about telomere length and mortality in breast cancer survivors.
METHODS:
We measured peripheral blood leukocyte telomere length at two time points in women enrolled in a multiethnic, prospective cohort of stage I to stage IIIA breast cancer survivors diagnosed between 1995 and 1999 with a median follow-up of 11.2 years. We evaluated associations between telomere length measured at mean 6 (baseline; LTL0; n = 611) and 30 months (LTL30; n = 478) after diagnosis and the change between those time points (n = 478), with breast cancer-specific and all-cause mortality using Cox proportional hazards models adjusted for possible confounders. Statistical tests were two-sided.
RESULTS:
There were 135 deaths, of which 74 were due to breast cancer. Neither baseline nor 30-month telomere length was associated with either all-cause or breast cancer-specific mortality (LTL0: hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.67 to 1.02; HR = 0.88; 95% CI = 0.67 to 1.15; LTL30: HR = 0.78, 95% CI = 0.59 to 1.05; HR = 0.86; 95% = CI = 0.58 to 1.26, respectively). However, participants whose telomeres shortened between baseline and 30 months were at a statistically significantly increased risk of breast cancer-specific (HR = 3.03; 95% CI = 1.11 to 8.18) and all-cause mortality (HR = 2.38; 95% CI = 1.28 to 4.39) compared with participants whose telomeres lengthened. When follow-up was censored at 5-years after diagnosis, LTL0 (HR = 0.66; 95% CI = 0.45 to 0.96), LTL30 (HR = 0.51; 95% CI = 0.29 to 0.92), and change in telomere length (HR = 3.45; 95% CI = 1.11 to 10.75) were statistically significantly associated with all-cause mortality.
CONCLUSIONS:
Telomere shortening was associated with increased risk of breast cancer-specific and all-cause mortality, suggesting that change in blood telomere length over time could be a biomarker of prognosis. Research on determinants of telomere length and change is needed.
PMID: 24627273
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