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Epigenome-wide methylation in DNA from peripheral blood as a marker of risk for breast cancer

  • Epidemiology
  • Published:
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Abstract

Aberrant DNA methylation is a key feature of breast carcinoma. We aimed to test the association between breast cancer risk and epigenome-wide methylation in DNA from peripheral blood. Nested case–control study within the prospective Melbourne Collaborative Cohort Study. DNA was extracted from before-diagnosis blood samples (420 incident cases and matched controls). Methylation was measured with the Illumina Infinium Human Methylation 450 BeadChip array. Odds ratio (OR) for epigenome-wide methylation, quantified as the mean beta values across the CpGs, in relation to breast cancer risk were estimated using conditional logistic regression. Overall, the OR for breast cancer was 0.42 (95 % CI 0.20–0.90) for the top versus bottom quartile of epigenome-wide DNA methylation and the OR for a one standard deviation increment was 0.69 (95 % CI 0.50–0.95; test for linear trend, p = 0.02). Epigenome-wide DNA methylation of CpGs within functional promoters was associated with an increased risk, whereas epigenome-wide DNA methylation of genomic regions outside promoters was associated with decreased risk (test for heterogeneity, p = 0.0002). The increased risk associated with epigenome-wide DNA methylation in functional promoters did not vary by time between blood collection and diagnosis, whereas the inverse association with epigenome-wide DNA methylation outside functional promoters was strongest when the interval from blood collection to diagnosis was less than 5 years and weakest for the longest interval. Epigenome-wide methylation in DNA extracted from peripheral blood collected before diagnosis may have potential utility as markers of breast cancer risk and for early detection.

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Acknowledgments

We would like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the Melbourne Collaborative Cohort Study, the original investigators, program managers and the diligent team who recruited the participants and who continue working on follow-up. The methylation measures were conducted by the Australian Genome Research Facility (AGRF) in Melbourne. This work was supported by grants from the National Health and Medical Research Council (Grant number 1011618); and the Victorian Breast Cancer Research Consortium.

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Authors and Affiliations

  1. Cancer Epidemiology Centre, Cancer Council of Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia

    Gianluca Severi, Dallas R. English, Graham G. Giles & Laura Baglietto

  2. School of Population and Global Health, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, VIC, Australia

    Gianluca Severi, Dallas R. English, John L. Hopper, Graham G. Giles & Laura Baglietto

  3. Human Genetic Foundation, Turin, Italy

    Gianluca Severi

  4. Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, VIC, Australia

    Melissa C. Southey & Helen Tsimiklis

  5. Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative, Carlton, VIC, 3010, Australia

    Chol-hee Jung & Andrew Lonie

  6. Department of Pathology, Alfred Hospital, Melbourne, VIC, Australia

    Catriona McLean

  7. Department of Medicine, Monash University, Melbourne, VIC, Australia

    Catriona McLean

  8. Seoul National University, Seoul, Korea

    John L. Hopper

  9. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    Graham G. Giles

Authors
  1. Gianluca Severi
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  2. Melissa C. Southey
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  3. Dallas R. English
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Correspondence to Laura Baglietto.

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Severi, G., Southey, M.C., English, D.R. et al. Epigenome-wide methylation in DNA from peripheral blood as a marker of risk for breast cancer. Breast Cancer Res Treat 148, 665–673 (2014). https://doi.org/10.1007/s10549-014-3209-y

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  • DOI: https://doi.org/10.1007/s10549-014-3209-y

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