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.