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@ARTICLE{Li:180173,
author = {X. Li$^*$ and B. Schöttker$^*$ and B. Holleczek$^*$ and H.
Brenner$^*$},
title = {{A}ssociations of {DNA} methylation algorithms of aging and
cancer risk: {R}esults from a prospective cohort study.},
journal = {EBioMedicine},
volume = {81},
issn = {2352-3964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2022-01145},
pages = {104083},
year = {2022},
note = {#EA:C070#LA:C070#LA:C120#},
abstract = {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.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.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.The DNAm algorithms, particularly the
MRscore-8CpGs, have potential to contribute to site-specific
cancer risk prediction.The ESTHER study was funded by grants
from the Baden-Württemberg state Ministry of Science,
Research and Arts (Stuttgart, Germany), the Federal Ministry
of Education and Research (Berlin, Germany), the Federal
Ministry of Family Affairs, Senior Citizens, Women and Youth
(Berlin, Germany), and the Saarland State Ministry of
Health, Social Affairs, Women and the Family (Saarbrücken,
Germany). The work of Xiangwei Li was supported by a grant
from Fondazione Cariplo (Bando Ricerca Malattie
invecchiamento, #2017-0653).},
keywords = {Age acceleration (Other) / Cancer risk (Other) / DNA
methylation (Other) / Epigenetic clock (Other)},
cin = {C070 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35636319},
doi = {10.1016/j.ebiom.2022.104083},
url = {https://inrepo02.dkfz.de/record/180173},
}