The Significant Associations between Epigenetic Clocks and Bladder Cancer Risks.

Area of Science:

• Gerontology
• Oncology
• Epigenetics

Background:

• Bladder cancer disproportionately affects older adults, with over 75% of cases in individuals aged 65 and older.
• Accelerated biological aging is a known risk factor for various cancers.
• The relationship between epigenetic clocks, indicators of biological age, and bladder cancer risk is not well understood.

Purpose of the Study:

• To investigate the association between four established epigenetic clocks (HannumAge, HorvathAge, GrimAge, PhenoAge) and bladder cancer risk.
• To determine if accelerated biological aging predicts increased susceptibility to bladder cancer.

Main Methods:

• A large case-control study design was employed.
• Weighted genetic risk scores (GRS) were constructed using single nucleotide polymorphisms (SNPs) associated with epigenetic clocks.
• Mendelian randomization (MR) methods, including inverse-variance weighting (IVW), were utilized to assess causality.

Main Results:

• Higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR=1.69 and OR=1.09, respectively).
• Mendelian randomization analyses confirmed the association between HannumAge, HorvathAge, and bladder cancer risk.
• GrimAge and PhenoAge showed no significant association with bladder cancer risk.

Conclusions:

• This study provides the first evidence linking accelerated biological aging, as indicated by specific epigenetic clocks, to a higher risk of bladder cancer.
• The findings suggest that biological aging, beyond chronological age, is a relevant factor in bladder cancer etiology.