端粒功能障碍：一种潜在的癌症易感因素。

Telomere dysfunction: a potential cancer predisposition factor.

作者信息

Wu Xifeng, Amos Christopher I, Zhu Yong, Zhao Hua, Grossman Barton H, Shay Jerry W, Luo Sherry, Hong Waun Ki, Spitz Margaret R

机构信息

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

出版信息

J Natl Cancer Inst. 2003 Aug 20;95(16):1211-8. doi: 10.1093/jnci/djg011.

DOI:10.1093/jnci/djg011

PMID:12928346

Abstract

BACKGROUND

Genetic instability associated with telomere dysfunction (i.e., short telomeres) is an early event in tumorigenesis. We investigated the association between telomere length and cancer risk in four ongoing case-control studies.

METHODS

All studies had equal numbers of case patients and matched control subjects (92 for head and neck cancer, 135 for bladder cancer, 54 for lung cancer, and 32 for renal cell carcinoma). Telomere length was measured in peripheral blood lymphocytes from study participants. Genetic instability was assessed with the comet assay. Patient and disease characteristics were collected and analyzed for associations with risk for these cancers. All statistical tests were two-sided.

RESULTS

Telomeres were statistically significantly shorter in patients with head and neck cancer (6.5 kilobases [kb]) than in control subjects (7.4 kb) (difference = 0.9 kb, 95% confidence interval [CI] = 0.5 to 1.2 kb; P<.001). Nine percent of patients with head and neck cancer were in the longest quartile of telomere length, whereas 59% were in the shortest quartile. Similar patterns were observed for lung, renal cell, and bladder cancer. When subjects were categorized into telomere length quartiles defined by the distribution in control subjects, the following inverse relationship between telomere length and cancer risk was observed: adjusted odds ratios [ORs] for decreasing quartiles = 0.84 (95% CI = 0.36 to 1.97), 1.77 (95% CI = 0.72 to 4.36), and 5.11 (95% CI = 1.90 to 13.77). In stratified analysis, we found a suggestive greater-than-additive interaction between smoking status and telomere length: for ever smokers with short telomeres, OR = 25.05 (95% CI = 6.91 to 90.73); for never smokers with short telomeres, OR = 6.18 (95% CI = 1.72 to 22.13); and for ever smokers with long telomeres, OR = 6.49 (95% CI = 1.54 to 27.38). Telomere length was statistically significantly and inversely associated with baseline and mutagen-induced genetic instability.

CONCLUSION

Short telomeres appear to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.

摘要

背景

与端粒功能障碍相关的基因不稳定（即短端粒）是肿瘤发生的早期事件。我们在四项正在进行的病例对照研究中调查了端粒长度与癌症风险之间的关联。

方法

所有研究的病例患者和匹配对照对象数量相等（头颈癌92例，膀胱癌135例，肺癌54例，肾细胞癌32例）。测量研究参与者外周血淋巴细胞中的端粒长度。用彗星试验评估基因不稳定情况。收集患者和疾病特征并分析其与这些癌症风险的关联。所有统计检验均为双侧检验。

结果

头颈癌患者的端粒在统计学上显著短于对照对象（6.5千碱基[kb]对7.4 kb）（差值 = 0.9 kb，95%置信区间[CI] = 0.5至1.2 kb；P<0.001）。9%的头颈癌患者处于端粒长度最长的四分位数，而59%处于最短的四分位数。肺癌、肾细胞癌和膀胱癌也观察到类似模式。当根据对照对象的分布将受试者分为端粒长度四分位数时，观察到端粒长度与癌症风险之间存在以下负相关关系：四分位数降低时的调整比值比[OR]分别为0.84（95%CI = 0.36至1.97）、1.77（95%CI = 0.72至4.36）和5.11（95%CI = 1.90至13.77）。在分层分析中，我们发现吸烟状态与端粒长度之间存在提示性的大于相加的相互作用：对于端粒短的曾经吸烟者，OR = 25.05（95%CI = 6.91至90.73）；对于端粒短的从不吸烟者，OR = 6.18（95%CI = 1.72至22.13）；对于端粒长的曾经吸烟者，OR = 6.49（95%CI = 1.54至27.38）。端粒长度与基线及诱变剂诱导的基因不稳定在统计学上显著负相关。