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

doi:10.1186/s13148-015-0125-x

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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Abstract

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 language	English
Article number	92
Number of pages	9
Journal	Clinical Epigenetics
Volume	7
Early online date	4 Sept 2015
DOIs	https://doi.org/10.1186/s13148-015-0125-x
Publication status	Published - 4 Sept 2015

Bibliographical note

Date of Acceptance: 17/08/2015

Acknowledgements
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.

Keywords

imprinting
methylation
breast cancer
invasive ductal carcinoma
ductal carcinoma in situ

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Breast cancer risk and imprinting methylation in blood
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Paul Haggarty, Deputy Director
- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Personal Chair
Person: Academic

Cite this

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title = "Breast cancer risk and imprinting methylation in blood",

abstract = "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.",

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note = "Date of Acceptance: 17/08/2015 Acknowledgements 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.",

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T1 - Breast cancer risk and imprinting methylation in blood

AU - Harrison, Kristina

AU - Hoad, Gwen

AU - Scott, Paula

AU - Simpson, Louise

AU - Horgan, Graham W

AU - Smyth, Elizabeth

AU - Heys, Steven D

AU - Haggarty, Paul

N1 - Date of Acceptance: 17/08/2015 Acknowledgements 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.

PY - 2015/9/4

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N2 - 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.

AB - 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.

KW - imprinting

KW - methylation

KW - breast cancer

KW - invasive ductal carcinoma

KW - ductal carcinoma in situ

U2 - 10.1186/s13148-015-0125-x

DO - 10.1186/s13148-015-0125-x

M3 - Article

C2 - 26347357

SN - 1868-7075

VL - 7

JO - Clinical Epigenetics

JF - Clinical Epigenetics

M1 - 92

ER -

Breast cancer risk and imprinting methylation in blood

Abstract

Bibliographical note

Keywords

UN SDGs

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Paul Haggarty, Deputy Director

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