Heritable DNA methylation marks associated with susceptibility to breast cancer

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)
16 Downloads (Pure)

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.

Original languageEnglish
Article number867
Pages (from-to)1-12
Number of pages12
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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