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Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer

BACKGROUND: Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age acceleration”, has been shown to predict age-related disease and mortality. We aimed...

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Autores principales: Beynon, Rhona A., Ingle, Suzanne M., Langdon, Ryan, May, Margaret, Ness, Andy, Martin, Richard M., Suderman, Matthew, Ingarfield, Kate, Marioni, Riccardo E., McCartney, Daniel L., Waterboer, Tim, Pawlita, Michael, Relton, Caroline, Smith, George Davey, Richmond, Rebecca C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725548/
https://www.ncbi.nlm.nih.gov/pubmed/34980250
http://dx.doi.org/10.1186/s13148-021-01220-4
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author Beynon, Rhona A.
Ingle, Suzanne M.
Langdon, Ryan
May, Margaret
Ness, Andy
Martin, Richard M.
Suderman, Matthew
Ingarfield, Kate
Marioni, Riccardo E.
McCartney, Daniel L.
Waterboer, Tim
Pawlita, Michael
Relton, Caroline
Smith, George Davey
Richmond, Rebecca C.
author_facet Beynon, Rhona A.
Ingle, Suzanne M.
Langdon, Ryan
May, Margaret
Ness, Andy
Martin, Richard M.
Suderman, Matthew
Ingarfield, Kate
Marioni, Riccardo E.
McCartney, Daniel L.
Waterboer, Tim
Pawlita, Michael
Relton, Caroline
Smith, George Davey
Richmond, Rebecca C.
author_sort Beynon, Rhona A.
collection PubMed
description BACKGROUND: Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age acceleration”, has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration and a DNA methylation-based mortality risk score with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000. We investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvath and IEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno), one optimised to predict lifespan (AgeAccelGrim) and a DNA methylation-based predictor of mortality (ZhangScore). Cox regression models were first used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of epigenetic age acceleration with all-cause mortality in people with oropharyngeal cancer (n = 408; 105 deaths). The added prognostic value of epigenetic markers compared to a clinical model including age, sex, TNM stage and HPV status was then evaluated. RESULTS: IEAAHannum and AgeAccelGrim were associated with mortality risk after adjustment for clinical and lifestyle factors (HRs per standard deviation [SD] increase in age acceleration = 1.30 [95% CI 1.07, 1.57; p = 0.007] and 1.40 [95% CI 1.06, 1.83; p = 0.016], respectively). There was weak evidence that the addition of AgeAccelGrim to the clinical model improved 3-year mortality prediction (area under the receiver operating characteristic curve: 0.80 vs. 0.77; p value for difference = 0.069). CONCLUSION: In the setting of a large, clinical cohort of individuals with head and neck cancer, our study demonstrates the potential of epigenetic markers of ageing to enhance survival prediction in people with oropharyngeal cancer, beyond established prognostic factors. Our findings have potential uses in both clinical and non-clinical contexts: to aid treatment planning and improve patient stratification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01220-4.
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spelling pubmed-87255482022-01-06 Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer Beynon, Rhona A. Ingle, Suzanne M. Langdon, Ryan May, Margaret Ness, Andy Martin, Richard M. Suderman, Matthew Ingarfield, Kate Marioni, Riccardo E. McCartney, Daniel L. Waterboer, Tim Pawlita, Michael Relton, Caroline Smith, George Davey Richmond, Rebecca C. Clin Epigenetics Research BACKGROUND: Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age acceleration”, has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration and a DNA methylation-based mortality risk score with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000. We investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvath and IEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno), one optimised to predict lifespan (AgeAccelGrim) and a DNA methylation-based predictor of mortality (ZhangScore). Cox regression models were first used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of epigenetic age acceleration with all-cause mortality in people with oropharyngeal cancer (n = 408; 105 deaths). The added prognostic value of epigenetic markers compared to a clinical model including age, sex, TNM stage and HPV status was then evaluated. RESULTS: IEAAHannum and AgeAccelGrim were associated with mortality risk after adjustment for clinical and lifestyle factors (HRs per standard deviation [SD] increase in age acceleration = 1.30 [95% CI 1.07, 1.57; p = 0.007] and 1.40 [95% CI 1.06, 1.83; p = 0.016], respectively). There was weak evidence that the addition of AgeAccelGrim to the clinical model improved 3-year mortality prediction (area under the receiver operating characteristic curve: 0.80 vs. 0.77; p value for difference = 0.069). CONCLUSION: In the setting of a large, clinical cohort of individuals with head and neck cancer, our study demonstrates the potential of epigenetic markers of ageing to enhance survival prediction in people with oropharyngeal cancer, beyond established prognostic factors. Our findings have potential uses in both clinical and non-clinical contexts: to aid treatment planning and improve patient stratification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01220-4. BioMed Central 2022-01-03 /pmc/articles/PMC8725548/ /pubmed/34980250 http://dx.doi.org/10.1186/s13148-021-01220-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Beynon, Rhona A.
Ingle, Suzanne M.
Langdon, Ryan
May, Margaret
Ness, Andy
Martin, Richard M.
Suderman, Matthew
Ingarfield, Kate
Marioni, Riccardo E.
McCartney, Daniel L.
Waterboer, Tim
Pawlita, Michael
Relton, Caroline
Smith, George Davey
Richmond, Rebecca C.
Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
title Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
title_full Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
title_fullStr Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
title_full_unstemmed Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
title_short Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
title_sort epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725548/
https://www.ncbi.nlm.nih.gov/pubmed/34980250
http://dx.doi.org/10.1186/s13148-021-01220-4
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