Breast cancer risk and imprinting methylation in blood

Clinical Epigenetics

Paul Haggarty¹  Steven D. Heys²  Elizabeth Smyth³  Graham W. Horgan⁴  Louise Simpson²  Paula Scott¹  Gwen Hoad¹  Kristina Harrison¹ 

[1] Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, UK;Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, University Medical Buildings, Foresterhill, Aberdeen, UK;Aberdeen Royal Infirmary, Ward 308, Foresterhill, Aberdeen, UK;Biomathematics and Statistics Scotland, Aberdeen, UK

关键词: Ductal carcinoma in situ;    Invasive ductal carcinoma;    Breast cancer;    Methylation;    Imprinting;   

Others  :  1225847
DOI  :  10.1186/s13148-015-0125-x

 received in 2015-06-20, accepted in 2015-08-17,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Harrison et al.

【 图 表 】

Fig. 1.

Fig. 2.

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