Association between biological aging and lung cancer risk: Cohort study and Mendelian randomization analysis

Zhimin Ma; Chen Zhu; Hui Wang; Mengmeng Ji; Yanqian Huang; Xiaoxia Wei; Jing Zhang; Yuzhuo Wang; Rong Yin; Juncheng Dai; Lin Xu; Hongxia Ma; Zhibin Hu; Guangfu Jin; Meng Zhu; Hongbing Shen

doi:10.1016/j.isci.2023.106018

Association between biological aging and lung cancer risk: Cohort study and Mendelian randomization analysis

iScience. 2023 Jan 19;26(3):106018. doi: 10.1016/j.isci.2023.106018. eCollection 2023 Mar 17.

Authors

Zhimin Ma^{1

2}, Chen Zhu^{2

3

4}, Hui Wang², Mengmeng Ji^{1

2}, Yanqian Huang², Xiaoxia Wei², Jing Zhang², Yuzhuo Wang^{2

5}, Rong Yin⁵, Juncheng Dai^{2

6}, Lin Xu⁵, Hongxia Ma^{2

6

7}, Zhibin Hu^{2

6}, Guangfu Jin^{1

2

6}, Meng Zhu^{2

6}, Hongbing Shen^{1

2

3

7}

Affiliations

¹ Department of Epidemiology, School of Public Health, Southeast University, Nanjing 210009, China.
² Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
³ Department of Cancer Prevention, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China.
⁴ Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
⁵ Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China.
⁶ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
⁷ Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing 100000, China.

Abstract

Chronological age only represents the passage of time, whereas biological age reflects the physiology states and the susceptibility to morbidity and mortality. The association between biological age and lung cancer risk remains controversial. Hence, we conducted a prospective analysis in the UK Biobank study and two-sample Mendelian randomization analysis to investigate this association. Biological aging was evaluated by PhenoAgeAccel, derived from routine clinical biomarkers. Independent of chronological age, PhenoAgeAccel was positively associated with the risk of overall and histological subtypes of lung cancer. There was a joint effect of PhenoAgeAccel and genetics in lung cancer incidence. In Mendelian randomization analysis, the genetically predicted PhenoAgeAccel was associated with the increased risk of overall lung cancer, small cell, and squamous cell carcinoma. Our findings suggest PhenoAgeAccel is an independent risk factor for lung cancer, which could be incorporated with polygenic risk score to identify high-risk individuals for lung cancer.

Keywords: Cancer; Health sciences; Risk stratification.