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外周血白细胞端粒长度与中国人群结直肠癌风险相关。

Telomere length in peripheral blood leukocytes is associated with risk of colorectal cancer in Chinese population.

机构信息

Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

The Chengdu Centers for Disease Control and Prevention, Chengdu, Sichuan, China.

出版信息

PLoS One. 2014 Feb 3;9(2):e88135. doi: 10.1371/journal.pone.0088135. eCollection 2014.

Abstract

BACKGROUND

Human telomeres, tandem repeats of TTAGGG nucleotides at the ends of chromosomes, are essential for maintaining genomic integrity and stability. Results of previous epidemiologic studies about the association of telomere length with risk of colorectal cancer (CRC) have been conflicting.

METHODS

A case-control study was conducted in a Han population in Wuhan, central China. The relative telomere length (RTL) was measured in peripheral blood leukocytes (PBLs) using quantitative real-time polymerase chain reaction (PCR) in 628 CRC cases and 1,256 age and sex frequency matched cancer-free controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression models to evaluate the association between RTL and CRC risk.

RESULTS

Using median RTL in the controls as the cutoff, individuals with shorter RTL were associated with a significantly increased risk of CRC (adjusted OR = 1.27, 95%CI: 1.05-1.55). When participants were further categorized into 3 and 4 groups according to the tertile and quartile RTL values of controls, significant relationships were still observed between shorter RTL and increased CRC risk (OR per tertile = 1.13, 95%CI: 1.00-1.28, P(trend) = 0.045; OR per quartile = 1.12, 95%CI: 1.03-1.23, P(trend) = 0.012). In stratified analyses, significant association between shorter RTL and increased CRC risk was found in females, individuals younger than 60 years old, never smokers and never drinkers.

CONCLUSIONS

This study suggested that short telomere length in PBLs was significantly associated with an increased risk of CRC in Chinese Han population. Further validation in large prospective studies and investigation of the biologic mechanisms are warranted.

摘要

背景

人类端粒是染色体末端的 TTAGGG 核苷酸串联重复序列,对于维持基因组的完整性和稳定性至关重要。先前关于端粒长度与结直肠癌(CRC)风险之间关联的流行病学研究结果存在争议。

方法

在中国中部武汉市的汉族人群中进行了一项病例对照研究。使用定量实时聚合酶链反应(PCR)测量 628 例 CRC 病例和 1256 例年龄和性别匹配的无癌对照者外周血白细胞(PBL)中的相对端粒长度(RTL)。使用无条件逻辑回归模型计算比值比(OR)和 95%置信区间(95%CI),以评估 RTL 与 CRC 风险之间的关联。

结果

使用对照组中的中位数 RTL 作为截断值,较短 RTL 的个体与 CRC 风险显著增加相关(校正 OR = 1.27,95%CI:1.05-1.55)。当根据对照组 RTL 的三分位和四分位值将参与者进一步分为 3 组和 4 组时,仍观察到较短 RTL 与 CRC 风险增加之间存在显著关系(每三分位 RTL 增加的 OR = 1.13,95%CI:1.00-1.28,P(趋势)= 0.045;每四分位 RTL 增加的 OR = 1.12,95%CI:1.03-1.23,P(趋势)= 0.012)。在分层分析中,在女性、年龄小于 60 岁、从不吸烟和从不饮酒的个体中,较短 RTL 与 CRC 风险增加之间存在显著关联。

结论

本研究表明,PBL 中的短端粒长度与中国汉族人群 CRC 风险增加显著相关。需要在大型前瞻性研究中进一步验证,并研究其生物学机制。

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