Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?
Purpose As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer. Method...
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| Veröffentlicht in: | Breast cancer research and treatment 2020-05, Vol.181 (1), p.135-144 |
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| creator | Do, Whitney L. Conneely, Karen Gabram-Mendola, Sheryl Krishnamurti, Uma D’Angelo, Olivia Miller-Kleinhenz, Jasmine Gogineni, Keerthi Torres, Mylin McCullough, Lauren E. |
| description | Purpose
As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer.
Methods
Genome-wide DNA methylation was measured in the breast cancer tumor tissue of 96 women using the EPIC array. To examine the association between obesity and tumor methylation, linear regression models were used—regressing methylation
β
value for each cytosine and guanine (CpG) site on body mass index adjusting for covariates. Significance was set at false discovery rate (FDR) |
| doi_str_mv | 10.1007/s10549-020-05605-6 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2385707519</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A621914212</galeid><sourcerecordid>A621914212</sourcerecordid><originalsourceid>FETCH-LOGICAL-c473t-3e573a5be7e9152ceab5d31831ad267952dc534e21a00788b7a3beb805c8a3cd3</originalsourceid><addsrcrecordid>eNp9kU9rFTEUxYMo9rX6BVxIQBA3U_NnMknclFKsCoVuFJchk7mvL3Vm8szNLN63N89XrRWRLALJ7xzuuYeQF5ydcsb0W-RMtbZhgjVMdUw13SOy4krLRguuH5MV451uOsO6I3KMeMsYs5rZp-RICiE7I-yKfL3uAWPZNR4xhegLDHSCstmNvsQ00zjTPoPHQssypYzvqKfbhBj7EegY52-0JDpE3PpctTQtJaQJ8OwZebL2I8Lzu_uEfLl8__niY3N1_eHTxflVE1otSyOhjutVDxosVyKA79UguZHcD6LTVokhKNmC4L4mNqbXXvbQG6aC8TIM8oS8Ofhuc_q-ABY3RQwwjn6GtKAT0ijNtOK2oq_-Qm_Tkuc6XaVs21pmtLmnbvwILs7rVLIPe1N33glueSu4qNTpP6h6BphiSDOsY31_IHj9h2ADfiwbTOOyXzI-BMUBDLmuOcPabXOcfN45zty-dneo3dXa3c_aXVdFL--iLf0Ew2_Jr54rIA8A1q_5BvJ99v_Y_gCTxrVs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2394490878</pqid></control><display><type>article</type><title>Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Do, Whitney L. ; Conneely, Karen ; Gabram-Mendola, Sheryl ; Krishnamurti, Uma ; D’Angelo, Olivia ; Miller-Kleinhenz, Jasmine ; Gogineni, Keerthi ; Torres, Mylin ; McCullough, Lauren E.</creator><creatorcontrib>Do, Whitney L. ; Conneely, Karen ; Gabram-Mendola, Sheryl ; Krishnamurti, Uma ; D’Angelo, Olivia ; Miller-Kleinhenz, Jasmine ; Gogineni, Keerthi ; Torres, Mylin ; McCullough, Lauren E.</creatorcontrib><description>Purpose
As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer.
Methods
Genome-wide DNA methylation was measured in the breast cancer tumor tissue of 96 women using the EPIC array. To examine the association between obesity and tumor methylation, linear regression models were used—regressing methylation
β
value for each cytosine and guanine (CpG) site on body mass index adjusting for covariates. Significance was set at false discovery rate (FDR) < 0.05. In the top 20 CpG sites, we explored the interactions with race and estrogen receptor (ER) status. We used multivariable Cox-proportional hazard models to examine whether methylation in the top 20 sites was associated with all-cause mortality.
Results
While none of the CpG sites passed the FDR threshold for significance, among the top 20 CpG sites, we observed interactions with race (
TOMM20
) and ER status (
PSMB1
,
QSOX1
and
PHF1
). The same CpG sites in
TOMM20
,
PSMB1,
and
QSOX1
were associated with all-cause mortality.
Conclusions
We identified novel interactions between obesity-associated methylation and both race and ER status in genes that have been associated with tumor regulation. Our data suggest that dysregulation in two sites may associate with all-cause mortality.</description><identifier>ISSN: 0167-6806</identifier><identifier>ISSN: 1573-7217</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-020-05605-6</identifier><identifier>PMID: 32236829</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Analysis ; Black or African American - statistics & numerical data ; Body Mass Index ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Breast Neoplasms - surgery ; Cancer ; Cancer research ; CpG Islands ; Cytosine ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Epidemiology ; Epigenesis, Genetic ; Estrogen ; Estrogen receptors ; Female ; Follow-Up Studies ; Genomes ; Guanine ; Health aspects ; Health risk assessment ; Humans ; Medical colleges ; Medicine ; Medicine & Public Health ; Methylation ; Middle Aged ; Mortality ; Obesity ; Obesity - physiopathology ; Oncology ; Oncology, Experimental ; Prognosis ; Pyrimidines ; Receptor, ErbB-2 - metabolism ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - metabolism ; Regression analysis ; Risk factors ; Survival Rate ; Tumors ; White People - statistics & numerical data</subject><ispartof>Breast cancer research and treatment, 2020-05, Vol.181 (1), p.135-144</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-3e573a5be7e9152ceab5d31831ad267952dc534e21a00788b7a3beb805c8a3cd3</citedby><cites>FETCH-LOGICAL-c473t-3e573a5be7e9152ceab5d31831ad267952dc534e21a00788b7a3beb805c8a3cd3</cites><orcidid>0000-0001-8977-9951</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-020-05605-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-020-05605-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32236829$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Do, Whitney L.</creatorcontrib><creatorcontrib>Conneely, Karen</creatorcontrib><creatorcontrib>Gabram-Mendola, Sheryl</creatorcontrib><creatorcontrib>Krishnamurti, Uma</creatorcontrib><creatorcontrib>D’Angelo, Olivia</creatorcontrib><creatorcontrib>Miller-Kleinhenz, Jasmine</creatorcontrib><creatorcontrib>Gogineni, Keerthi</creatorcontrib><creatorcontrib>Torres, Mylin</creatorcontrib><creatorcontrib>McCullough, Lauren E.</creatorcontrib><title>Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer.
Methods
Genome-wide DNA methylation was measured in the breast cancer tumor tissue of 96 women using the EPIC array. To examine the association between obesity and tumor methylation, linear regression models were used—regressing methylation
β
value for each cytosine and guanine (CpG) site on body mass index adjusting for covariates. Significance was set at false discovery rate (FDR) < 0.05. In the top 20 CpG sites, we explored the interactions with race and estrogen receptor (ER) status. We used multivariable Cox-proportional hazard models to examine whether methylation in the top 20 sites was associated with all-cause mortality.
Results
While none of the CpG sites passed the FDR threshold for significance, among the top 20 CpG sites, we observed interactions with race (
TOMM20
) and ER status (
PSMB1
,
QSOX1
and
PHF1
). The same CpG sites in
TOMM20
,
PSMB1,
and
QSOX1
were associated with all-cause mortality.
Conclusions
We identified novel interactions between obesity-associated methylation and both race and ER status in genes that have been associated with tumor regulation. Our data suggest that dysregulation in two sites may associate with all-cause mortality.</description><subject>Analysis</subject><subject>Black or African American - statistics & numerical data</subject><subject>Body Mass Index</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - surgery</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>CpG Islands</subject><subject>Cytosine</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epidemiology</subject><subject>Epigenesis, Genetic</subject><subject>Estrogen</subject><subject>Estrogen receptors</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genomes</subject><subject>Guanine</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Obesity</subject><subject>Obesity - physiopathology</subject><subject>Oncology</subject><subject>Oncology, Experimental</subject><subject>Prognosis</subject><subject>Pyrimidines</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Regression analysis</subject><subject>Risk factors</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>White People - statistics & numerical data</subject><issn>0167-6806</issn><issn>1573-7217</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kU9rFTEUxYMo9rX6BVxIQBA3U_NnMknclFKsCoVuFJchk7mvL3Vm8szNLN63N89XrRWRLALJ7xzuuYeQF5ydcsb0W-RMtbZhgjVMdUw13SOy4krLRguuH5MV451uOsO6I3KMeMsYs5rZp-RICiE7I-yKfL3uAWPZNR4xhegLDHSCstmNvsQ00zjTPoPHQssypYzvqKfbhBj7EegY52-0JDpE3PpctTQtJaQJ8OwZebL2I8Lzu_uEfLl8__niY3N1_eHTxflVE1otSyOhjutVDxosVyKA79UguZHcD6LTVokhKNmC4L4mNqbXXvbQG6aC8TIM8oS8Ofhuc_q-ABY3RQwwjn6GtKAT0ijNtOK2oq_-Qm_Tkuc6XaVs21pmtLmnbvwILs7rVLIPe1N33glueSu4qNTpP6h6BphiSDOsY31_IHj9h2ADfiwbTOOyXzI-BMUBDLmuOcPabXOcfN45zty-dneo3dXa3c_aXVdFL--iLf0Ew2_Jr54rIA8A1q_5BvJ99v_Y_gCTxrVs</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Do, Whitney L.</creator><creator>Conneely, Karen</creator><creator>Gabram-Mendola, Sheryl</creator><creator>Krishnamurti, Uma</creator><creator>D’Angelo, Olivia</creator><creator>Miller-Kleinhenz, Jasmine</creator><creator>Gogineni, Keerthi</creator><creator>Torres, Mylin</creator><creator>McCullough, Lauren E.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8977-9951</orcidid></search><sort><creationdate>20200501</creationdate><title>Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?</title><author>Do, Whitney L. ; Conneely, Karen ; Gabram-Mendola, Sheryl ; Krishnamurti, Uma ; D’Angelo, Olivia ; Miller-Kleinhenz, Jasmine ; Gogineni, Keerthi ; Torres, Mylin ; McCullough, Lauren E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-3e573a5be7e9152ceab5d31831ad267952dc534e21a00788b7a3beb805c8a3cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Black or African American - statistics & numerical data</topic><topic>Body Mass Index</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - surgery</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>CpG Islands</topic><topic>Cytosine</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Epidemiology</topic><topic>Epigenesis, Genetic</topic><topic>Estrogen</topic><topic>Estrogen receptors</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genomes</topic><topic>Guanine</topic><topic>Health aspects</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methylation</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Obesity</topic><topic>Obesity - physiopathology</topic><topic>Oncology</topic><topic>Oncology, Experimental</topic><topic>Prognosis</topic><topic>Pyrimidines</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Regression analysis</topic><topic>Risk factors</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>White People - statistics & numerical data</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Do, Whitney L.</creatorcontrib><creatorcontrib>Conneely, Karen</creatorcontrib><creatorcontrib>Gabram-Mendola, Sheryl</creatorcontrib><creatorcontrib>Krishnamurti, Uma</creatorcontrib><creatorcontrib>D’Angelo, Olivia</creatorcontrib><creatorcontrib>Miller-Kleinhenz, Jasmine</creatorcontrib><creatorcontrib>Gogineni, Keerthi</creatorcontrib><creatorcontrib>Torres, Mylin</creatorcontrib><creatorcontrib>McCullough, Lauren E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Do, Whitney L.</au><au>Conneely, Karen</au><au>Gabram-Mendola, Sheryl</au><au>Krishnamurti, Uma</au><au>D’Angelo, Olivia</au><au>Miller-Kleinhenz, Jasmine</au><au>Gogineni, Keerthi</au><au>Torres, Mylin</au><au>McCullough, Lauren E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Obesity-associated methylation in breast tumors: a possible link to disparate outcomes?</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>181</volume><issue>1</issue><spage>135</spage><epage>144</epage><pages>135-144</pages><issn>0167-6806</issn><issn>1573-7217</issn><eissn>1573-7217</eissn><abstract>Purpose
As a primary risk factor and modifier of breast cancer incidence and prognosis, obesity may contribute to race disparities in breast cancer outcomes. This study examined association between obesity and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer.
Methods
Genome-wide DNA methylation was measured in the breast cancer tumor tissue of 96 women using the EPIC array. To examine the association between obesity and tumor methylation, linear regression models were used—regressing methylation
β
value for each cytosine and guanine (CpG) site on body mass index adjusting for covariates. Significance was set at false discovery rate (FDR) < 0.05. In the top 20 CpG sites, we explored the interactions with race and estrogen receptor (ER) status. We used multivariable Cox-proportional hazard models to examine whether methylation in the top 20 sites was associated with all-cause mortality.
Results
While none of the CpG sites passed the FDR threshold for significance, among the top 20 CpG sites, we observed interactions with race (
TOMM20
) and ER status (
PSMB1
,
QSOX1
and
PHF1
). The same CpG sites in
TOMM20
,
PSMB1,
and
QSOX1
were associated with all-cause mortality.
Conclusions
We identified novel interactions between obesity-associated methylation and both race and ER status in genes that have been associated with tumor regulation. Our data suggest that dysregulation in two sites may associate with all-cause mortality.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32236829</pmid><doi>10.1007/s10549-020-05605-6</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8977-9951</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2020-05, Vol.181 (1), p.135-144 |
| issn | 0167-6806 1573-7217 1573-7217 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2385707519 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Analysis Black or African American - statistics & numerical data Body Mass Index Breast cancer Breast Neoplasms - genetics Breast Neoplasms - mortality Breast Neoplasms - pathology Breast Neoplasms - surgery Cancer Cancer research CpG Islands Cytosine Deoxyribonucleic acid DNA DNA Methylation Epidemiology Epigenesis, Genetic Estrogen Estrogen receptors Female Follow-Up Studies Genomes Guanine Health aspects Health risk assessment Humans Medical colleges Medicine Medicine & Public Health Methylation Middle Aged Mortality Obesity Obesity - physiopathology Oncology Oncology, Experimental Prognosis Pyrimidines Receptor, ErbB-2 - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Regression analysis Risk factors Survival Rate Tumors White People - statistics & numerical data |
| title | Obesity-associated methylation in breast tumors: a possible link to disparate outcomes? |
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