Blood-Based Epigenetic Age Acceleration and Incident Colorectal Cancer Risk: Findings from a Population-Based Case–Control Study

Author:

Malyutina Sofia1,Chervova Olga2ORCID,Maximov Vladimir1ORCID,Nikitenko Tatiana1,Ryabikov Andrew1,Voevoda Mikhail1ORCID

Affiliation:

1. Research Institute of Internal and Preventive Medicine-Branch of Institute of Cytology and Genetics SB RAS, Novosibirsk 630089, Russia

2. University College London, London WC1E6BT, UK

Abstract

This study investigates the association between epigenetic age acceleration (EAA) derived from DNA methylation and the risk of incident colorectal cancer (CRC). We utilized data from a random population sample of 9,360 individuals (men and women, aged 45–69) from the HAPIEE Study who had been followed up for 16 years. A nested case–control design yielded 35 incident CRC cases and 354 matched controls. Six baseline epigenetic age (EA) measures (Horvath, Hannum, PhenoAge, Skin and Blood (SB), BLUP, and Elastic Net (EN)) were calculated along with their respective EAAs. After adjustment, the odds ratios (ORs) for CRC risk per decile increase in EAA ranged from 1.20 (95% CI: 1.04–1.39) to 1.44 (95% CI: 1.21–1.76) for the Horvath, Hannum, PhenoAge, and BLUP measures. Conversely, the SB and EN EAA measures showed borderline inverse associations with ORs of 0.86–0.87 (95% CI: 0.76–0.99). Tertile analysis reinforced a positive association between CRC risk and four EAA measures (Horvath, Hannum, PhenoAge, and BLUP) and a modest inverse relationship with EN EAA. Our findings from a prospective population-based-case-control study indicate a direct association between incident CRC and four markers of accelerated baseline epigenetic age. In contrast, two markers showed a negative association or no association. These results warrant further exploration in larger cohorts and may have implications for CRC risk assessment and prevention.

Funder

Russian Science Foundation

Publisher

MDPI AG

Reference64 articles.

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