Associations of DNA methylation algorithms of aging and cancer risk: results from a prospective cohort study
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...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 May 2022
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| In: |
EBioMedicine
Year: 2022, Volume: 81, Pages: 1-9 |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2022.104083 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ebiom.2022.104083 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S235239642200264X 
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| Author Notes: | Xiangwei Li, Ben Schöttker, Bernd Holleczek, and Hermann Brenner |
| Summary: | 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. |
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| Item Description: | Gesehen am 17.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2022.104083 |