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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157462/ https://www.ncbi.nlm.nih.gov/pubmed/35636319 http://dx.doi.org/10.1016/j.ebiom.2022.104083 |
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author | Li, Xiangwei Schöttker, Ben Holleczek, Bernd Brenner, Hermann |
author_facet | Li, Xiangwei Schöttker, Ben Holleczek, Bernd Brenner, Hermann |
author_sort | Li, Xiangwei |
collection | PubMed |
description | 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. FUNDING: 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). |
format | Online Article Text |
id | pubmed-9157462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-91574622022-06-22 Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study Li, Xiangwei Schöttker, Ben Holleczek, Bernd Brenner, Hermann eBioMedicine Articles 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. FUNDING: 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). Elsevier 2022-05-27 /pmc/articles/PMC9157462/ /pubmed/35636319 http://dx.doi.org/10.1016/j.ebiom.2022.104083 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Li, Xiangwei Schöttker, Ben Holleczek, Bernd Brenner, Hermann Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study |
title | Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study |
title_full | Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study |
title_fullStr | Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study |
title_full_unstemmed | Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study |
title_short | Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study |
title_sort | associations of dna methylation algorithms of aging and cancer risk: results from a prospective cohort study |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157462/ https://www.ncbi.nlm.nih.gov/pubmed/35636319 http://dx.doi.org/10.1016/j.ebiom.2022.104083 |
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