Associations of DNA methylation algorithms of aging and cancer risk

• Verfasst von: Li, Xiangwei [VerfasserIn]
• Verfasst von: Schöttker, Ben [VerfasserIn]
• Verfasst von: Holleczek, Bernd [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Titel: Associations of DNA methylation algorithms of aging and cancer risk
• Titelzusatz: results from a prospective cohort study
• Verf.angabe: Xiangwei Li, Ben Schöttker, Bernd Holleczek, and Hermann Brenner
• E-Jahr: 2022
• Jahr: 27 May 2022
• Umfang: 9 S.
• Fussnoten: Gesehen am 17.05.2023
• Titel Quelle: Enthalten in: EBioMedicine
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 2014
• Jahr Quelle: 2022
• Band/Heft Quelle: 81(2022) vom: Mai, Artikel-ID 104083, Seite 1-9
• ISSN Quelle: 2352-3964
• DOI: doi:10.1016/j.ebiom.2022.104083
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Age acceleration
• Sach-SW: Cancer risk
• Sach-SW: DNA methylation
• Sach-SW: Epigenetic clock
• K10plus-PPN: 1845618785

Abstract

Background - Previous studies have shown that three DNA methylation (DNAm) based algorithms of aging, DNAm PhenoAge acceleration (AgeAccelPheno), DNAm GrimAge acceleration (AgeAccelGrim), and mortality risk score (MRscore), to be strong predictors of mortality and aging related outcomes. We aimed to investigate if and to what extent these algorithms predict cancer. - Methods - In four subsets (n = 727, 1003, 910, and 412) of a population-based cohort from Germany, DNA methylation in whole blood was measured using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay (Illumina.Inc, San Diego, CA, USA). AgeAccelPheno, AgeAccelGrim, and a revised MRscore based on 8 CpGs only (MRscore-8CpGs), were calculated. Hazard ratios (HRs) were calculated to assess associations of the three DNAm algorithms with total cancer risk and risk of invasive breast, lung, prostate, and colorectal cancer incidence. - Findings - During 17 years of follow-up, a total of 697 malignant tumors (thereof breast cancer = 75, lung cancer = 146, prostate cancer = 114, colorectal cancer = 155) were observed. All three algorithms showed strong positive associations with lung cancer risk in a dose response manner, with adjusted HRs per SD increase in AgeAccelPheno, AgeAccelGrim, and MRscore-8CpGs, of 1·37 (1·03-1·82), 1·74 (1·11-2·73), and 2·06 (1·39-3·06), respectively. By contrast, strong inverse associations were seen with breast cancer risk [adjusted HRs 0·65 (0·49-0·86), 0·45 (0·25-0·80), and 0·42 (0·25-0·70), respectively]. Weak positive associations of MRscore-8CpGs were seen with total cancer risk. - Interpretation - The DNAm algorithms, particularly the MRscore-8CpGs, have potential to contribute to site-specific cancer risk prediction.