Journal article

Heritable DNA methylation marks associated with susceptibility to breast cancer

Jihoon E Joo, James G Dowty, Roger L Milne, Ee Ming Wong, Pierre-Antoine Dugue, Dallas English, John L Hopper, David E Goldgar, Graham G Giles, Melissa C Southey



Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable methylation marks associated with breast cancer susceptibility by studying 25 Australian multiple-case breast cancer families. Here we report genome-wide DNA methylation measured in 210 peripheral blood DNA samples provided by family members using the Infinium HumanMethylation450. We develop and apply a new statistical method to identify heritable methylation marks based on complex segregation analysis. We estimate carrier probabilities for the 1000 most heritable methylation marks based on family structure, and we use Cox proportional ..

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Awarded by USA National Cancer Institute

Awarded by National Health and Medical Research Council

Awarded by National Breast Cancer Foundation

Funding Acknowledgements

The Australian site of Breast Cancer Family Registry was supported by grant UM1 CA164920 from the USA National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the USA Government or the BCFR. We thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. 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, programme managers and the diligent team who recruited the participants and who continue working on follow-up. The MCCS methylation work was supported by the National Health and Medical Research Council (Grant number 1011618); and the Victorian Breast Cancer Research Consortium. M.C.S. is a Senior Research Fellow and J.L.H. is a Senior Principal Research Fellow of the National Health and Medical Research Council of Australia. This work was supported by an Early Career Research Award to JEJ from The University of Melbourne.