Biological Aging Measures Based on Blood DNA Methylation and Risk of Cancer: A Prospective Study.
Level 3 - non-randomized controlled study
Prospective cohort study with nested case-control analysis
PubMed 33442664 · doi:10.1093/jncics/pkaa109
What was done
Researchers evaluated prospective associations between three blood DNA methylation-based aging biomarkers (age-adjusted PhenoAge, GrimAge, and predicted telomere length) and risk of seven cancers within the Melbourne Collaborative Cohort Study: colorectal (n = 813), gastric (n = 165), kidney (n = 139), lung (n = 327), mature B-cell (n = 423), prostate (n = 846), and urothelial (n = 404). Rate ratios (RRs) per standard deviation (SD) were estimated using conditional logistic regression adjusted for sociodemographic, lifestyle, anthropometric variables, and detailed smoking metrics (status, pack-years, starting age, time since quitting). Analyses also assessed time since blood collection, cancer subtypes, and potential non-linearity.
What was found
Age-adjusted PhenoAge was associated with risk of colorectal, kidney, lung, mature B-cell, and urothelial cancers (RR per SD ≈ 1.2 to 1.3). Age-adjusted GrimAge showed similar patterns but a larger association with lung cancer (RR per SD = 1.82, 95% CI = 1.44 to 2.30) after adjustment for smoking and other risk factors. For cancer overall, fully adjusted RRs per SD were 1.13 (95% CI = 1.07 to 1.19) for PhenoAge and 1.12 (95% CI = 1.05 to 1.20) for GrimAge. These associations were stronger for diagnoses within 5 years of blood draw: RR = 1.29 (95% CI = 1.15 to 1.44) for PhenoAge and RR = 1.19 (95% CI = 1.06 to 1.33) for GrimAge. The abstract reported no specific numerical results for predicted telomere length.
Why it matters
Second-generation epigenetic clocks (PhenoAge and GrimAge) predict multi-cancer incidence independently of standard risk factors, identifying biological aging processes that may aid in cancer risk stratification, particularly for lung cancer.
Limits
The study is limited to a single Australian cohort. Stronger associations observed within 5 years of blood draw suggest possible reverse causation from occult pre-diagnostic malignancy altering blood methylation profiles. The abstract omits results for the third tested biomarker (predicted telomere length), and residual confounding in observational analyses cannot be fully excluded.
Cited by
- supports Blood DNA methylation biomarkers, such as GrimAge, statistically predict future onset of cancer.