Heritable DNA methylation marks associated with susceptibility to breast cancer
Date
2018-02-28
Authors
Joo, Jihoon
Dowty, James
Milne, Roger
Ming Wong, E.
Dugue, Pierre-Antoine
Sexton, Adrienne
Christian, Alice
Trainer, Alison
Shelling, Andrew
Blackburn, Anneke
Journal Title
Journal ISSN
Volume Title
Publisher
Macmillan Publishers Ltd
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.
Description
Keywords
Citation
Collections
Source
Nature Communications
Type
Journal article
Book Title
Entity type
Access Statement
Open Access
License Rights
Creative Commons Attribution 4.0 International License
Restricted until
Downloads
File
Description