白细胞端粒长度（LTL）与多种疾病，包括癌症有关。然而，有关LTL与肺癌风险之间的关联的研究结果在以前的观察性研究中是不确定和不一致的。本前瞻性队列研究包括来自英国生物样本库的425,146名年龄为37-73岁的参与者的数据。定量聚合酶链反应（qPCR）用于测量基线DNA样本中的LTL。采用多元Cox比例风险模型评估LTL与肺癌风险之间的关系。单位长度范围（IQR）增加的LTL与肺癌风险的增加呈正相关（风险比[Hazard ratio, HR]为1.09 [95%可信区间（CI）1.03-1.16]）。最高LTL五分位数的参与者与最低五分位数的参与者相比，患肺癌的风险约增加25％（HR为1.25 [95%CI 1.09-1.45]）。单位IQR增加的LTL与肺癌风险的关系在组织学亚型腺癌（HR 1.30 [95% CI 1.18-1.43]）、女性性别（HR 1.16 [95% CI 1.06-1.26]）、非吸烟者（HR 1.45 [95% CI 1.23-1.71]）和有高遗传风险的肺癌个体（HR 1.18 [95% CI 1.03-1.34]）中更为显著。令人惊讶的是，每个IQR增加的LTL与非吸烟者中的肺腺癌（HR 1.56 [95% CI 1.24-1.96]）和鳞状细胞癌（HR 2.01 [95% CI 1.13-3.56]）的风险都有所增加。较长的LTL与肺癌的风险增加有关，尤其是对于非吸烟者中的腺癌和鳞状细胞癌。结果提示LTL作为无创生物标志物有潜力用于肺癌的早期筛查，尤其适用于通常被忽视的非吸烟者。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Leukocyte telomere length (LTL) is associated with a wide variety of diseases, including cancer. However, findings regarding the association between LTL and the risk for lung cancer have been inconclusive and inconsistent across previous observational studies.This prospective cohort study included data from 425,146 participants 37-73 years of age housed in the UK Biobank. Quantitative polymerase chain reaction (qPCR) was used to measure LTL in baseline DNA samples. A multivariate Cox proportional hazards model was used to evaluate the relationship between LTL and the risk for lung cancer.An increase in LTL per interquartile range (IQR) was associated with a 9% increase in the risk for lung cancer (hazard ratio [HR] 1.09 [95% confidence interval (CI) 1.03-1.16]). Participants in the highest LTL quintile exhibited an approximately 25% elevated risk for developing lung cancer (HR 1.25 [95% CI 1.09-1.45]) compared with those in the lowest quintile. The relationship between per IQR increase in LTL and elevated risk for lung cancer was greater in the histological subtype of adenocarcinoma (HR 1.30 [95% CI 1.18-1.43]), female sex (HR 1.16 [95% CI 1.06-1.26]), non-smokers (HR 1.45 [95% CI 1.23-1.71]), and individuals with high genetic risk for lung cancer (HR 1.18 [95% CI 1.03-1.34]), respectively. Surprisingly, a per IQR increase in LTL was associated with increased risks for both lung adenocarcinoma (HR 1.56 [95% CI 1.24-1.96]) and squamous cell carcinoma (HR 2.01 [95% CI 1.13-3.56]) in never smokers.Longer LTL was associated with an elevated risk for lung cancer, particularly for adenocarcinoma and squamous cell carcinoma in never smokers. The results suggest the potential of telomeres as non-invasive biomarkers for the early screening of lung cancer, particularly in non-smokers, who are typically overlooked.Copyright © 2023 Elsevier B.V. All rights reserved.