Breast cancer risk and imprinting methylation in blood.
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.
Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, UK.
Kristina
K
Harrison
Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, UK.
Gwen
G
Hoad
Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, UK.
Paula
P
Scott
Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, University Medical Buildings, Foresterhill, Aberdeen, UK.
Louise
L
Simpson
Biomathematics and Statistics Scotland, Aberdeen, UK.
Graham W
GW
Horgan
Aberdeen Royal Infirmary, Ward 308, Foresterhill, Aberdeen, UK.
Elizabeth
E
Smyth
Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, University Medical Buildings, Foresterhill, Aberdeen, UK.
Steven D
SD
Heys
Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, UK.
Paul
P
Haggarty
Breast cancer; Ductal carcinoma in situ; Imprinting; Invasive ductal carcinoma; Methylation