白细胞端粒长度与胰腺癌风险的关联：一项前瞻性研究的结果。
Association between leukocyte telomere length and the risk of pancreatic cancer: Findings from a prospective study.
机构信息
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States of America.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA, United States of America.
出版信息
PLoS One. 2019 Aug 29;14(8):e0221697. doi: 10.1371/journal.pone.0221697. eCollection 2019.
INTRODUCTION
Telomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study.
METHODS
The Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors.
RESULTS
Longer telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25-3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17-8.11) for adenocarcinoma patients and 1.47 (0.43-5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22-5.13) and 1.63 (0.66-4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk.
CONCLUSIONS
The present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer.
简介
端粒和端粒酶在维持染色体完整性和基因组稳定性方面发挥着重要作用。最近的流行病学数据显示，端粒长度过短和过长均与胰腺癌风险增加相关，这一发现存在不一致性。我们在一项基于人群的队列研究中前瞻性地研究了端粒长度与胰腺癌风险之间的关系。
方法
新加坡华人健康研究于 1993 年至 1998 年在新加坡招募了 63257 名年龄在 45 至 74 岁的华人。在 26540 名参与者中，使用经过验证的单染多重定量聚合酶链反应方法定量检测外周血白细胞中端粒的相对长度，其中 116 名参与者在平均 13 年的随访后被诊断患有胰腺癌。使用 Cox 比例风险回归方法计算端粒长度与胰腺癌风险之间的风险比（HR）及其 95%置信区间（CI），并进行了混杂因素调整。
结果
较长的端粒与更高的胰腺癌风险显著相关（Ptrend = 0.02）。与最低四分位数相比，端粒长度最高四分位数的受试者发生胰腺癌的 HR 为 2.18（95%CI：1.25-3.80）。在分层分析中，这种关联在胰腺腺癌患者中仍然存在，但在胰腺非腺癌患者中不存在。在连续尺度上，腺癌患者的 HRs 和 95%CI 为 3.08（1.17-8.11），非腺癌患者的 HRs 和 95%CI 为 1.47（0.43-5.06）。与最低四分位数相比，端粒长度最高四分位数的 HRs 和 95%CI 分别为腺癌患者的 2.50（1.22-5.13）和非腺癌患者的 1.63（0.66-4.03）。从采集血液测量端粒长度到诊断癌症的随访时间（中位数=8.0，范围：5.0 个月至 16.2 年）对端粒长度与胰腺癌风险之间的关联没有显著影响。
结论
本研究表明，较长的端粒与总体胰腺癌风险增加相关。
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