Associations of Combined Phenotypic Aging and Genetic Risk with Incident Cancer: A Prospective Cohort Study

作者：Lijun Bian, Zhimin Ma, Xiangjin Fu, Ji Chen, Tianpei Wang, Caiwang Yan, Juncheng Dai, Hongxia Ma, Zhibin Hu, Hongbing Shen, Lu Wang, Meng Zhu, Guangfu Jin · 发表于：medRxiv · 年份：2023 · DOI：10.1101/2023.09.27.23296204 · 被引用次数：7 · 研究领域：Genetic factors in colorectal cancer、Epigenetics and DNA Methylation、Cancer Genomics and Diagnostics

Abstract 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 9 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, 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 ri...