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

Research output: Contribution to journalArticleResearchpeer-review

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
Number of pages12
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 28 Feb 2018

Cite this

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title = "Heritable DNA methylation marks associated with susceptibility to breast cancer",
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.",
author = "Joo, {Jihoon E.} and Dowty, {James G.} and Milne, {Roger L.} and Wong, {Ee Ming} and Dugu{\'e}, {Pierre Antoine} and KConFab and Dallas English and Hopper, {John L.} and Goldgar, {David E.} and Giles, {Graham G.} and Southey, {Melissa C.}",
year = "2018",
month = "2",
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doi = "10.1038/s41467-018-03058-6",
language = "English",
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Heritable DNA methylation marks associated with susceptibility to breast cancer. / Joo, Jihoon E.; Dowty, James G.; Milne, Roger L.; Wong, Ee Ming; Dugué, Pierre Antoine; KConFab; English, Dallas; Hopper, John L.; Goldgar, David E.; Giles, Graham G.; Southey, Melissa C.

In: Nature Communications, Vol. 9, No. 1, 867, 28.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Heritable DNA methylation marks associated with susceptibility to breast cancer

AU - Joo, Jihoon E.

AU - Dowty, James G.

AU - Milne, Roger L.

AU - Wong, Ee Ming

AU - Dugué, Pierre Antoine

AU - KConFab

AU - English, Dallas

AU - Hopper, John L.

AU - Goldgar, David E.

AU - Giles, Graham G.

AU - Southey, Melissa C.

PY - 2018/2/28

Y1 - 2018/2/28

N2 - 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.

AB - 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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