端粒长度与癌症发病风险和癌症死亡率。

Telomere length and risk of incident cancer and cancer mortality.

机构信息

Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.

出版信息

JAMA. 2010 Jul 7;304(1):69-75. doi: 10.1001/jama.2010.897.

DOI:10.1001/jama.2010.897

PMID:20606151

Abstract

CONTEXT

Telomeres are essential to preserve the integrity of the genome. Critically short telomeres lead to replicative cell senescence and chromosomal instability and may thereby increase cancer risk.

OBJECTIVE

To determine the association between baseline telomere length and incident cancer and cancer mortality.

DESIGN, SETTING, AND PARTICIPANTS: Leukocyte telomere length was measured by quantitative polymerase chain reaction in 787 participants free of cancer at baseline in 1995 from the prospective, population-based Bruneck Study in Italy.

MAIN OUTCOME MEASURES

Incident cancer and cancer mortality over a follow-up period of 10 years (1995-2005 with a follow-up rate of 100%).

RESULTS

A total of 92 of 787 participants (11.7%) developed cancer (incidence rate, 13.3 per 1000 person-years). Short telomere length at baseline was associated with incident cancer independently of standard cancer risk factors (multivariable hazard ratio [HR] per 1-SD decrease in log(e)-transformed telomere length, 1.60; 95% confidence interval [CI], 1.30-1.98; P < .001). Compared with participants in the longest telomere length group, the multivariable HR for incident cancer was 2.15 (95% CI, 1.12-4.14) in the middle length group and 3.11 (95% CI, 1.65-5.84) in the shortest length group (P < .001). Incidence rates were 5.1 (95% CI, 2.9-8.7) per 1000 person-years in the longest telomere length group, 14.2 (95% CI, 10.0-20.1) per 1000 person-years in the middle length group, and 22.5 (95% CI, 16.9-29.9) per 1000 person-years in the shortest length group. The association equally applied to men and women and emerged as robust under a variety of circumstances. Furthermore, short telomere length was associated with cancer mortality (multivariable HR per 1-SD decrease in log(e)-transformed telomere length, 2.13; 95% CI, 1.58-2.86; P < .001) and individual cancer subtypes with a high fatality rate.

CONCLUSION

In this study population, there was a statistically significant inverse relationship between telomere length and both cancer incidence and mortality.

摘要

背景

端粒对于保护基因组的完整性至关重要。端粒严重缩短会导致细胞复制性衰老和染色体不稳定，从而可能增加癌症风险。

目的

确定基线端粒长度与癌症发病和癌症死亡的相关性。

设计、地点和参与者：意大利布伦瑞克前瞻性人群研究在 1995 年招募了 787 名无癌症的参与者，使用实时聚合酶链反应定量检测白细胞端粒长度。

主要观察指标

10 年随访期间（1995-2005 年，随访率为 100%）的癌症发病和癌症死亡。

结果

共有 787 名参与者中的 92 名（11.7%）发生了癌症（发病率为 13.3/1000 人年）。端粒长度在基线时较短与癌症发病独立相关，不受标准癌症风险因素的影响（每 1-SD 对数转换端粒长度降低，多变量危险比[HR]为 1.60；95%置信区间[CI]，1.30-1.98；P<.001）。与端粒长度最长组的参与者相比，中端粒长度组的多变量 HR 为 2.15（95%CI，1.12-4.14），最短组为 3.11（95%CI，1.65-5.84）（P<.001）。最长端粒长度组的发病率为 5.1/1000 人年，中端粒长度组为 14.2/1000 人年，最短组为 22.5/1000 人年（95%CI，16.9-29.9）。该相关性在男性和女性中同样适用，并且在各种情况下均表现稳健。此外，端粒长度较短与癌症死亡率相关（每 1-SD 对数转换端粒长度降低，多变量 HR 为 2.13；95%CI，1.58-2.86；P<.001），与死亡率较高的个别癌症亚型也相关。