Breast cancer risk and imprinting methylation in blood

Kristina Harrison, Gwen Hoad, Paula Scott, Louise Simpson, Graham W Horgan, Elizabeth Smyth, Steven D Heys, Paul Haggarty

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BACKGROUND: Altered DNA methylation of imprinted genes has been implicated in a range of cancers. Imprinting is established early in development, and some are maintained throughout the life course in multiple tissues, providing a plausible mechanism linking known early life factors to cancer risk. This study investigated methylation status of seven imprinted differentially methylated regions-PLAGL1/ZAC1, H19-ICR1, IGF2-DMR2, KvDMR-ICR2, RB1, SNRPN-DMR1 and PEG3-in blood samples from 189 women with the most common type of invasive breast cancer (invasive ductal carcinoma-IDC), 41 women with in situ breast cancer (ductal carcinoma in situ-DCIS) and 363 matched disease-free controls.

RESULTS: There was no evidence that imprinted gene methylation levels varied with age (between 25 and 87 years old), weight or height. Higher PEG3 methylation was associated with an elevated risk of IDC (odds ratio (OR) 1.065; 95 % confidence interval (CI) 1.002, 1.132; p = 0.042) and DCIS (OR 1.139; 95 % CI 1.027, 1.263; p = 0.013). The effect was stronger when in situ and invasive breast cancer were combined (OR 1.079; 95 % CI 1.020, 1.142; p = 0.008). DCIS breast cancer risk increased with higher KvDMR-ICR2 methylation (OR 1.395; 95 % CI 1.190, 1.635; p < 0.001) and lower PLAGL1/ZAC1 methylation (OR 0.905; 95 % CI 0.833, 0.982; p = 0.017). In a combined model, only KvDMR-ICR2 methylation remained significantly associated.

CONCLUSIONS: These findings may help to improve our understanding of the aetiology of breast cancer and the importance of early life factors in particular. Imprinting methylation status also has the potential to contribute to the development of improved screening and treatment strategies for women with, or at risk of, breast cancer.

Original languageEnglish
Article number92
Number of pages9
JournalClinical Epigenetics
Early online date4 Sept 2015
Publication statusPublished - 4 Sept 2015

Bibliographical note

Date of Acceptance: 17/08/2015

This study was supported by the Breast Cancer Campaign (2008MayPR46) and Fraserburgh Moonlight Prowl Breast Cancer Charity. PH, GH and GWH acknowledge the support of the Scottish Government. We would like to thank Val Bain and Michela Donnarumma for help with the data and sample collection.


  • imprinting
  • methylation
  • breast cancer
  • invasive ductal carcinoma
  • ductal carcinoma in situ


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