Association of telomere length with risk of lung cancer: A large prospective cohort study from the UK Biobank

Duoduo Han; Yiqun Zhu; Abira A Choudhry; Jun Cheng; Huaying Liang; Fengyu Lin; Qinyu Chang; Hong Liu; Pinhua Pan; Yan Zhang

doi:10.1016/j.lungcan.2023.107358

Association of telomere length with risk of lung cancer: A large prospective cohort study from the UK Biobank

Lung Cancer. 2023 Oct:184:107358. doi: 10.1016/j.lungcan.2023.107358. Epub 2023 Sep 3.

Authors

Duoduo Han¹, Yiqun Zhu¹, Abira A Choudhry², Jun Cheng³, Huaying Liang¹, Fengyu Lin¹, Qinyu Chang¹, Hong Liu⁴, Pinhua Pan⁵, Yan Zhang⁶

Affiliations

¹ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
² Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI 48109, USA.
³ Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁴ Department of Dermatology, Xiangya Hospital of Central South University, Changsha 41000, Hunan, China. Electronic address: hongliu1014@csu.edu.cn.
⁵ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Center of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha 410008, Hunan, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha 410008, Hunan, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha 410008, Hunan, China. Electronic address: pinhuapan668@csu.edu.cn.
⁶ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Center of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha 410008, Hunan, China; Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha 410008, Hunan, China; Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha 410008, Hunan, China. Electronic address: zhangy4290@csu.edu.cn.

PMID: 37696218
DOI: 10.1016/j.lungcan.2023.107358

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Genetic risk; Leukocyte telomere length (LTL); Lung cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma*
Biological Specimen Banks
Carcinoma, Squamous Cell*
Female
Humans
Lung Neoplasms* / epidemiology
Lung Neoplasms* / genetics
Prospective Studies
Telomere / genetics
United Kingdom / epidemiology