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Heritable DNA methylation marks associated with susceptibility to breast cancer

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Joo, Jihoon; Dowty, James; Milne, Roger; Ming Wong, E.; Dugue, Pierre-Antoine; Sexton, Adrienne; Christian, Alice; Trainer, Alison; Shelling, Andrew; Blackburn, Anneke; Fazio, Anna De; English, Dallas R.; Lindeman, Geoffrey J.; Campbell, Ian G.; Hickie, Ian B.; Tucker, Katherine M.; Jenkins, Mark A.

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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...[Show more]

dc.contributor.authorJoo, Jihoon
dc.contributor.authorDowty, James
dc.contributor.authorMilne, Roger
dc.contributor.authorMing Wong, E.
dc.contributor.authorDugue, Pierre-Antoine
dc.contributor.authorSexton, Adrienne
dc.contributor.authorChristian, Alice
dc.contributor.authorTrainer, Alison
dc.contributor.authorShelling, Andrew
dc.contributor.authorBlackburn, Anneke
dc.contributor.authorFazio, Anna De
dc.contributor.authorEnglish, Dallas R.
dc.contributor.authorLindeman, Geoffrey J.
dc.contributor.authorCampbell, Ian G.
dc.contributor.authorHickie, Ian B.
dc.contributor.authorTucker, Katherine M.
dc.contributor.authorJenkins, Mark A.
dc.date.accessioned2019-12-11T22:43:58Z
dc.date.available2019-12-11T22:43:58Z
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1885/192966
dc.description.abstractMendelian-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 hazards survival analysis to identify 24 methylation marks with corresponding carrier probabilities significantly associated with breast cancer. We replicate an association with breast cancer risk for four of the 24 marks using an independent nested case–control study. Here, we report a novel approach for identifying heritable DNA methylation marks associated with breast cancer risk.
dc.description.sponsorshipThe Australian site of Breast Cancer Family Registry was supported by grant UM1 CA164920 from the USA National Cancer Institute. kConFab is supported by a grant from the National Breast Cancer Foundation. 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.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherMacmillan Publishers Ltd
dc.rights© The Author(s) 2018
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceNature Communications
dc.titleHeritable DNA methylation marks associated with susceptibility to breast cancer
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume9
dc.date.issued2018-02-28
local.identifier.absfor111203 - Cancer Genetics
local.identifier.ariespublicationu3102795xPUB4
local.publisher.urlhttps://www.nature.com
local.type.statusPublished Version
local.contributor.affiliationJoo, Jihoon, The University of Melbourne
local.contributor.affiliationDowty, James, The University of Melbourne
local.contributor.affiliationMilne, Roger, The University of Melbourne
local.contributor.affiliationMing Wong, E., The University of Melbourne
local.contributor.affiliationDugue, Pierre-Antoine, The University of Melbourne
local.contributor.affiliationSexton, Adrienne, Royal Melbourne Hospital
local.contributor.affiliationChristian, Alice, Wellington Hospital
local.contributor.affiliationTrainer, Alison, Victorian Comprehensive Cancer Centre
local.contributor.affiliationShelling, Andrew, University of Auckland
local.contributor.affiliationBlackburn, Anneke, College of Health and Medicine, ANU
local.contributor.affiliationFazio, Anna De, Westmead Hospital
local.contributor.affiliationEnglish, Dallas R., Cancer Council Victoria
local.contributor.affiliationLindeman, Geoffrey J, Walter and Eliza Hall Institute of Medical Research
local.contributor.affiliationCampbell, Ian G., Peter MacCallum Cancer Centre
local.contributor.affiliationHickie, Ian B., University of Sydney
local.contributor.affiliationTucker, Katherine M., Prince of Wales Hospital
local.contributor.affiliationJenkins, Mark A., University of Melbourne
dc.relationhttp://purl.org/au-research/grants/nhmrc/1011618
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage12
local.identifier.doi10.1038/s41467-018-03058-6
local.identifier.absseo920102 - Cancer and Related Disorders
dc.date.updated2019-07-28T08:18:47Z
local.identifier.scopusID2-s2.0-85043262563
dcterms.accessRightsOpen Access
dc.provenanceThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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
dc.rights.licenseCreative Commons Attribution 4.0 International License
CollectionsANU Research Publications

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