Heritable DNA methylation marks associated with susceptibility to breast cancer
Jihoon E. Joo(The University of Melbourne), James G. Dowty(The University of Melbourne), Roger L. Milne(The University of Melbourne), Ee Ming Wong(The University of Melbourne), Pierre‐Antoine Dugué(The University of Melbourne), Dallas R. English(The University of Melbourne), John L. Hopper(The University of Melbourne), David E. Goldgar(The University of Melbourne), Graham G. Giles(The University of Melbourne), Melissa C. Southey(The University of Melbourne), kConFab(The Royal Melbourne Hospital), Adrienne Sexton(The Royal Melbourne Hospital), Alice Christian(Peter MacCallum Cancer Centre), Alison H. Trainer(Peter MacCallum Cancer Centre), Allan D. Spigelman(Peter MacCallum Cancer Centre), Andrew Fellows(University of Auckland), Andrew N. Shelling(University of Auckland), Anna de Fazio(Australian National University), Anneke C. Blackburn(Australian National University), Ashley Crook(Royal North Shore Hospital), Bettina Meiser(Royal Hobart Hospital), Briony Patterson(The University of Sydney), Christine L. Clarke(The University of Sydney), Christobel Saunders(Monash Medical Centre), Clare Hunt(The Royal Melbourne Hospital), Clare L. Scott(The Royal Melbourne Hospital), David J. Amor(Royal Children's Hospital), Deborah J. Marsh(Royal North Shore Hospital), Edward Edkins(Princess Margaret Hospital for Children), Elizabeth Salisbury(Women's and Children's Hospital), Eric Haan(Peter MacCallum Cancer Centre), Eveline Neidermayr(The Royal Melbourne Hospital), Finlay Macrae(South Australia Pathology), Gelareh Farshid(South Australia Pathology), Geoffrey J. Lindeman(The Royal Melbourne Hospital), Georgia Chenevix‐Trench(QIMR Berghofer Medical Research Institute), Graham J. Mann(Royal Adelaide Hospital), Grantley Gill(Royal Adelaide Hospital), Heather Thorne(Peter MacCallum Cancer Centre), Ian Campbell(Peter MacCallum Cancer Centre), Ian B. Hickie(The Royal Melbourne Hospital), Ingrid Winship(The Royal Melbourne Hospital), Jack Goldblatt(King Edward Memorial Hospital), James M. Flanagan(Royal Adelaide Hospital), James Kollias(Royal Adelaide Hospital), Jane E. Visvader(The Royal Melbourne Hospital), Jennifer Stone(The Royal Melbourne Hospital), Jessica Taylor(The Royal Melbourne Hospital), Jo Burke(The University of Queensland), Jodi M. Saunus(The University of Queensland), John Forbes(QIMR Berghofer Medical Research Institute), Jonathan Beesley(QIMR Berghofer Medical Research Institute), Judy Kirk(QIMR Berghofer Medical Research Institute), Juliet D. French(QIMR Berghofer Medical Research Institute), Kathy Tucker(St Vincent's Hospital Sydney), Kathy H. C. Wu(Peter MacCallum Cancer Centre), Kelly Phillips(Peter MacCallum Cancer Centre), Lara Lipton(Westmead Hospital), Leslie Andrews(Westmead Hospital), Elizabeth Lobb(University of Otago), Logan C. Walker(The Royal Melbourne Hospital), Maira Kentwell(The Royal Melbourne Hospital), Amanda B. Spurdle(The University of Queensland), Margaret C. Cummings(The University of Queensland), Margaret Gleeson(Monash Medical Centre), Marion Harris(The University of Melbourne), Mark A. Jenkins(Garvan Institute of Medical Research), Mary Anne Young(Royal Children's Hospital), Martin B. Delatycki(Royal Children's Hospital), Mathew Wallis(Royal Children's Hospital), Matthew Burgess(The University of Sydney), Melanie A. Price(The University of Sydney), Melissa A. Brown(The Royal Melbourne Hospital), Michael Bogwitz(The Royal Melbourne Hospital), Michael Field(Royal North Shore Hospital), Michael Friedländer(Royal Children's Hospital), Michael Gattas(Royal Brisbane and Women's Hospital), Mona Saleh(QIMR Berghofer Medical Research Institute), Nick Hayward(The Royal Melbourne Hospital), Nick Pachter(St John of God Subiaco Hospital), Paul A. Cohen(St John of God Subiaco Hospital), Pascal H. G. Duijf(The Royal Melbourne Hospital), Paul A. James(The Royal Melbourne Hospital), Peter T. Simpson(The University of Queensland), Peter C.C. Fong(Royal Prince Alfred Hospital), Phyllis Butow(Royal Prince Alfred Hospital), Rachael Williams(Westmead Hospital), Richard Kefford(John Hunter Hospital), Rodney J. Scott(Royal Prince Alfred Hospital), Rosemary L. Balleine(Royal Prince Alfred Hospital), Sarah‐Jane Dawson(The Royal Melbourne Hospital), Sheau Wen Lok(The Royal Melbourne Hospital), Shona O’Connell(Wollongong Hospital), Sian Greening(Peter MacCallum Cancer Centre), Sophie Nightingale(QIMR Berghofer Medical Research Institute), Stacey L. Edwards(QIMR Berghofer Medical Research Institute), Stephen B. Fox(Peter MacCallum Cancer Centre), Sue‐Anne McLachlan(The University of Queensland), Sunil R. Lakhani(The Royal Melbourne Hospital), Susan N. Thomas(The Royal Melbourne Hospital), Yoland Antill(Cabrini Hospital)
Cited by 116Open Access
Abstract
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 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.
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