Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer
Abstract Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinog...
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| Veröffentlicht in: | Human molecular genetics 2020-03, Vol.29 (4), p.662-673 |
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| container_title | Human molecular genetics |
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| creator | Salas, Lucas A Lundgren, Sara N Browne, Eva P Punska, Elizabeth C Anderton, Douglas L Karagas, Margaret R Arcaro, Kathleen F Christensen, Brock C |
| description | Abstract
Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an epigenome-wide association study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value |
| doi_str_mv | 10.1093/hmg/ddz301 |
| format | Article |
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Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an epigenome-wide association study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value <0.05). Nearly all CpG sites associated with a breast cancer diagnosis were hypomethylated in cases compared with controls and were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has utility as a biospecimen for prospective assessment of disease risk, for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddz301</identifier><identifier>PMID: 31943067</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adolescent ; Adult ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Case-Control Studies ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; General One ; Humans ; Middle Aged ; Milk, Human - chemistry ; Prognosis ; Prospective Studies ; Young Adult</subject><ispartof>Human molecular genetics, 2020-03, Vol.29 (4), p.662-673</ispartof><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-9c79f538f289fb801b57f292b471ca04d0994106019f6b14d98e73f86d1525433</citedby><cites>FETCH-LOGICAL-c408t-9c79f538f289fb801b57f292b471ca04d0994106019f6b14d98e73f86d1525433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31943067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salas, Lucas A</creatorcontrib><creatorcontrib>Lundgren, Sara N</creatorcontrib><creatorcontrib>Browne, Eva P</creatorcontrib><creatorcontrib>Punska, Elizabeth C</creatorcontrib><creatorcontrib>Anderton, Douglas L</creatorcontrib><creatorcontrib>Karagas, Margaret R</creatorcontrib><creatorcontrib>Arcaro, Kathleen F</creatorcontrib><creatorcontrib>Christensen, Brock C</creatorcontrib><title>Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>Abstract
Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an epigenome-wide association study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value <0.05). Nearly all CpG sites associated with a breast cancer diagnosis were hypomethylated in cases compared with controls and were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has utility as a biospecimen for prospective assessment of disease risk, for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Case-Control Studies</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>General One</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Milk, Human - chemistry</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Young Adult</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kM9LwzAUx4Mobk4v_gHSixeh7qVJ0-YijPkThnpQ8BbSJlmrbTOSbjL_eqt1Qy9e3nvwPu_74IPQMYZzDJyMi3o-VuqDAN5BQ0wZhBGkZBcNgTMaMg5sgA68fwXAjJJkHw0I5pQAS4bo5dFpVcp5Y31b5kHmtPRtUJfVW3B5Pwlq3RbrSralbQJZtdp9jz4om-Dd1rqrhQ2UXunKLjbHuWxy7Q7RnpGV10c_fYSer6-eprfh7OHmbjqZhTmFtA15nnATk9REKTdZCjiLExPxKKMJziVQBZxTDAwwNyzDVPFUJ8SkTOE4iikhI3TR5y6WWa1VrpvWyUosXFlLtxZWluLvpikLMbcrkQBLcYK7gLM-IHfWe6fN9haD-PIrOr-i99vBJ7-_bdGN0A447QG7XPwX9AlApoUh</recordid><startdate>20200313</startdate><enddate>20200313</enddate><creator>Salas, Lucas A</creator><creator>Lundgren, Sara N</creator><creator>Browne, Eva P</creator><creator>Punska, Elizabeth C</creator><creator>Anderton, Douglas L</creator><creator>Karagas, Margaret R</creator><creator>Arcaro, Kathleen F</creator><creator>Christensen, Brock C</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200313</creationdate><title>Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer</title><author>Salas, Lucas A ; Lundgren, Sara N ; Browne, Eva P ; Punska, Elizabeth C ; Anderton, Douglas L ; Karagas, Margaret R ; Arcaro, Kathleen F ; Christensen, Brock C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-9c79f538f289fb801b57f292b471ca04d0994106019f6b14d98e73f86d1525433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Case-Control Studies</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>General One</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Milk, Human - chemistry</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salas, Lucas A</creatorcontrib><creatorcontrib>Lundgren, Sara N</creatorcontrib><creatorcontrib>Browne, Eva P</creatorcontrib><creatorcontrib>Punska, Elizabeth C</creatorcontrib><creatorcontrib>Anderton, Douglas L</creatorcontrib><creatorcontrib>Karagas, Margaret R</creatorcontrib><creatorcontrib>Arcaro, Kathleen F</creatorcontrib><creatorcontrib>Christensen, Brock C</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salas, Lucas A</au><au>Lundgren, Sara N</au><au>Browne, Eva P</au><au>Punska, Elizabeth C</au><au>Anderton, Douglas L</au><au>Karagas, Margaret R</au><au>Arcaro, Kathleen F</au><au>Christensen, Brock C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2020-03-13</date><risdate>2020</risdate><volume>29</volume><issue>4</issue><spage>662</spage><epage>673</epage><pages>662-673</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>Abstract
Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an epigenome-wide association study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value <0.05). Nearly all CpG sites associated with a breast cancer diagnosis were hypomethylated in cases compared with controls and were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has utility as a biospecimen for prospective assessment of disease risk, for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>31943067</pmid><doi>10.1093/hmg/ddz301</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Breast Neoplasms - diagnosis Breast Neoplasms - genetics Breast Neoplasms - metabolism Case-Control Studies DNA Methylation Epigenesis, Genetic Female Gene Expression Regulation, Neoplastic General One Humans Middle Aged Milk, Human - chemistry Prognosis Prospective Studies Young Adult |
| title | Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer |
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