Article open access publication

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

European Journal of Cancer, Elsevier, ISSN 1879-0852

Volume 75, 2017

DOI:10.1016/j.ejca.2017.01.014, Dimensions: pub.1084071148, PMC: PMC5512160, PMID: 28259012,



  1. (1) International Agency For Research On Cancer, grid.17703.32
  2. (2) University of California, Los Angeles, grid.19006.3e
  3. (3) Aarhus University, grid.7048.b, AU
  4. (4) Cancer Epidemiology Centre, Cancer Council Victoria and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourn, Australia
  5. (5) Institut Gustave Roussy, grid.14925.3b
  6. (6) Human Genetics Foundation, grid.428948.b
  7. (7) German Cancer Research Center, grid.7497.d
  8. (8) German Institute of Human Nutrition, grid.418213.d
  9. (9) Hellenic Health Foundation, grid.424637.0
  10. (10) National and Kapodistrian University of Athens, grid.5216.0
  11. (11) Harvard University, grid.38142.3c
  12. (12) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  13. (13) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  14. (14) Cancer Registry and Histopathology Unit, “Civic M.P. Arezzo” Hospital, ASP Ragusa, Italy
  15. (15) University of Naples Federico II, grid.4691.a
  16. (16) National Institute for Public Health and the Environment, grid.31147.30
  17. (17) University Medical Center Utrecht, grid.7692.a
  18. (18) Imperial College London, grid.7445.2
  19. (19) The Arctic University of Norway, grid.10919.30
  20. (20) Cancer Registry of Norway, grid.418941.1
  21. (21) Folkhälsans Forskningscentrum, grid.428673.c
  22. (22) Karolinska Institute, grid.4714.6
  23. (23) Public Health Directorate, Asturias, Spain
  24. (24) Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
  25. (25) Andalusian School of Public Health, grid.413740.5
  26. (26) Institute of Health Carlos III, grid.413448.e
  27. (27) Instituto Murciano de Investigación Biosanitaria, grid.452553.0
  28. (28) Navarra Institute for Health Research (IdiSNA) Pamplona, Spain
  29. (29) Navarra Public Health Institute, Pamplona, Spain
  30. (30) Biodonostia, grid.432380.e
  31. (31) Ikerbasque, grid.424810.b
  32. (32) University of Oxford, grid.4991.5


AIM OF THE STUDY: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. METHODS: Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. RESULTS: We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007-1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007-1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020-1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03-1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. CONCLUSION: Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.


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2017: Unused

Research area: Medicine

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2017: Level 1

Research area: Medicine

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Times Cited: 61

Field Citation Ratio (FCR): 22.07

Relative Citation ratio (RCR): 4.74

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