外周血白细胞端粒长度变化与乳腺癌幸存者的死亡率。
Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors.
机构信息
Affiliations 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).
出版信息
J Natl Cancer Inst. 2014 Apr;106(4):dju035. doi: 10.1093/jnci/dju035. Epub 2014 Mar 13.
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.
背景
随着细胞分裂，端粒逐渐缩短是衰老的一个标志。短端粒与癌症风险增加有关，但关于乳腺癌幸存者中端粒长度与死亡率之间的关系存在矛盾的报告。
方法
我们在多民族前瞻性队列研究中，对 1995 年至 1999 年间诊断为 I 期至 IIIA 期乳腺癌的女性，在两次时间点测量外周血白细胞端粒长度，中位随访时间为 11.2 年。我们评估了在诊断后平均 6 个月（基线；LTL0；n = 611）和 30 个月（LTL30；n = 478）测量的端粒长度与这两个时间点之间的变化（n = 478）与乳腺癌特异性和全因死亡率之间的关系，使用 Cox 比例风险模型进行调整，以排除可能的混杂因素。统计检验为双侧检验。
结果
共有 135 人死亡，其中 74 人死于乳腺癌。基线和 30 个月时的端粒长度均与全因或乳腺癌特异性死亡率无关（LTL0：风险比[HR] = 0.83，95%置信区间[CI] = 0.67 至 1.02；HR = 0.88；95%CI = 0.67 至 1.15；LTL30：HR = 0.78，95%CI = 0.59 至 1.05；HR = 0.86；95%CI = 0.58 至 1.26）。然而，与端粒长度延长的参与者相比，端粒在基线和 30 个月之间缩短的参与者乳腺癌特异性（HR = 3.03；95%CI = 1.11 至 8.18）和全因死亡率（HR = 2.38；95%CI = 1.28 至 4.39）的风险显著增加。当随访截止到诊断后 5 年时，LTL0（HR = 0.66；95%CI = 0.45 至 0.96）、LTL30（HR = 0.51；95%CI = 0.29 至 0.92）和端粒长度变化（HR = 3.45；95%CI = 1.11 至 10.75）与全因死亡率显著相关。
结论
端粒缩短与乳腺癌特异性和全因死亡率风险增加相关，这表明随着时间的推移，血液端粒长度的变化可能是预后的生物标志物。需要研究端粒长度和变化的决定因素。
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