Objective:

To examine the association between accelerated biological aging and the risk of early-onset cancers across different generations.

Approach:

• Cohorts Analyzed: Data from 154,169 patients under 55 years in the UK Biobank and 10,262 patients in the All of Us Research Program were analyzed.
• Biological Aging Assessment: Biological aging was assessed using blood-based measures including PhenoAge, Klemera-Doubal method (KDM), and metabolomic aging scores.
• Primary Outcome: The primary outcome was the incidence of solid cancer diagnosed before 55 years.

Key Findings:

• Patients born between 1965 and 1974 had a 23% higher PhenoAge-defined age gap compared to those born between 1950 and 1954.
• Each 1-standard deviation increase in PhenoAge-defined age gap was associated with an 8% higher likelihood of early-onset solid cancer.
• Patients in the highest tertile of age gap had a 15% higher risk of early-onset solid cancer compared to those in the lowest tertile.
• The strongest associations were found for lung (57% higher likelihood), gastrointestinal (17% higher likelihood), and endometrial cancers (31% higher likelihood).
• Organ-specific aging analyses indicated immune-system aging was linked to early-onset lung cancer and adipose-tissue aging to early-onset colorectal cancer.

Interpretation:

Limitations:

• The study is observational and cannot establish causality.
• Residual confounding may exist despite adjustments for established risk factors.
• Some cancer-specific and organ-specific analyses were limited by small case numbers.
• Findings may not generalize beyond UK and US populations.
• Organ-specific aging analyses require independent validation.

Conclusion:

Sources:

• Nature Medicine