期刊
JNCI CANCER SPECTRUM
卷 5, 期 1, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/jncics/pkaa109
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资金
- Australian National Health and Medical Research Council (NHMRC) [1164455]
- VicHealth
- Cancer Council Victoria
- Australian NHMRC [209057, 251553, 504711]
- NHMRC [1011618, 1026892, 1027505, 1050198, 1043616, 1074383, 1061177]
- Victorian Cancer Agency [ECRF19020]
- Monash University, Melbourne, Australia
- National Health and Medical Research Council of Australia [1164455, 1074383, 1061177] Funding Source: NHMRC
Recent research examined the association between methylation-based measures of aging (PhenoAge and GrimAge) and cancer risk, revealing potential insights into the relationship between biological aging and cancer, particularly in relation to lung cancer.
Background: We previously investigated the association between 5 first-generation measures of epigenetic aging and cancer risk in the Melbourne Collaborative Cohort Study. This study assessed cancer risk associations for 3 recently developed methylation-based biomarkers of aging: PhenoAge, GrimAge, and predicted telomere length. Methods: We estimated rate ratios (RRs) for the association between these 3 age-adjusted measures and risk of colorectal (N = 813), gastric (N = 165), kidney (N = 139), lung (N = 327), mature B-cell (N = 423), prostate (N = 846), and urothelial (N = 404) cancer using conditional logistic regression models. We also assessed associations by time since blood draw and by cancer subtype, and we investigated potential nonlinearity. Results: We observed relatively strong associations of age-adjusted PhenoAge with risk of colorectal, kidney, lung, mature B-cell, and urothelial cancers (RR per SD was approximately 1.2-1.3). Similar findings were obtained for age-adjusted GrimAge, but the association with lung cancer risk was much larger (RR per SD = 1.82, 95% confidence interval [CI] = 1.44 to 2.30), after adjustment for smoking status, pack-years, starting age, time since quitting, and other cancer risk factors. Most associations appeared linear, larger than for the first-generation measures, and were virtually unchanged after adjustment for a large set of sociodemographic, lifestyle, and anthropometric variables. For cancer overall, the comprehensively adjusted rate ratio per SD was 1.13 (95% CI = 1.07 to 1.19) for PhenoAge and 1.12 (95% CI = 1.05 to 1.20) for GrimAge and appeared larger within 5 years of blood draw (RR = 1.29, 95% CI = 1.15 to 1.44 and 1.19, 95% CI = 1.06 to 1.33, respectively). Conclusions: The methylation-based measures PhenoAge and GrimAge may provide insights into the relationship between biological aging and cancer and be useful to predict cancer risk, particularly for lung cancer.
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