Seow Wei Jie, Cawthon Richard M, Purdue Mark P, Hu Wei, Gao Yu-Tang, Huang Wen-Yi, Weinstein Stephanie J, Ji Bu-Tian, Virtamo Jarmo, Hosgood H Dean, Bassig Bryan A, Shu Xiao-Ou, Cai Qiuyin, Xiang Yong-Bing, Min Shen, Chow Wong-Ho, Berndt Sonja I, Kim Christopher, Lim Unhee, Albanes Demetrius, Caporaso Neil E, Chanock Stephen, Zheng Wei, Rothman Nathaniel, Lan Qing
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland;
Department of Human Genetics, University of Utah, Salt Lake City, Utah;
Cancer Res. 2014 Aug 1;74(15):4090-8. doi: 10.1158/0008-5472.CAN-14-0459. Epub 2014 May 22.
We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Women's Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.
我们在一项汇总分析中研究了端粒长度与肺癌之间的关系，该分析整合了三项前瞻性队列研究的数据：在美国开展的前列腺、肺、结肠和卵巢（PLCO）癌筛查试验，参与对象为男性和女性；此前已发表的芬兰男性吸烟者α-生育酚、β-胡萝卜素癌症预防（ATBC）试验的数据；以及主要由从不吸烟者组成的上海女性健康研究（SWHS）。汇总人群包括847例病例和847例按研究、年龄和性别匹配的对照。采用单色多重定量聚合酶链反应（qPCR）法测量白细胞端粒长度。我们使用条件逻辑回归模型计算端粒长度与肺癌风险之间关联的比值比（OR）及其95%置信区间（CI），并对年龄和吸烟包年数进行了校正。在汇总分析中，较长的端粒长度与肺癌风险增加相关[按四分位数划分的OR（95%CI）：1.00；1.24（0.90 - 1.71）；1.27（0.91 - 1.78）；以及1.86（1.33 - 2.62）；P趋势 = 0.000022]。三项队列研究的结果一致，对于端粒长度非常长的受试者最为显著，即第四四分位数上半部分的端粒长度对应的肺癌风险[OR（95%CI）]，在PLCO试验、ATBC试验和SWHS中分别为2.41（1.28 - 4.52）、2.16（1.11 - 4.23）和3.02（1.39 - 6.58）。此外，该关联在采血后6年以上确诊的病例中仍然存在，在女性腺癌病例中尤为明显。白细胞DNA中的端粒长度可能是不同人群未来肺癌风险增加的生物标志物。
