Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study
Lijun Bian,
Zhimin Ma,
Xiangjin Fu,
Chen Ji,
Tianpei Wang,
Caiwang Yan,
Juncheng Dai,
Hongxia Ma,
Zhibin Hu,
Hongbing Shen,
Lu Wang,
Meng Zhu,
Guangfu Jin
Affiliations
Lijun Bian
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China
Zhimin Ma
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Xiangjin Fu
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Chen Ji
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Tianpei Wang
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
Caiwang Yan
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China; Department of Chronic Non-Communicable Disease Control, The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
Juncheng Dai
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China
Hongxia Ma
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China
Hongbing Shen
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China; Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, China
Lu Wang
Department of Chronic Non-Communicable Disease Control, The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China; Department of Chronic Non-Communicable Disease Control, The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health Nanjing Medical University, Nanjing, China; Department of Chronic Non-Communicable Disease Control, The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p<0.001; Beta = –0.98 in women, p<0.001). Conclusions: Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. Funding: This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).
