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Mendelian randomization analyses of associations between breast cancer and bone mineral density
The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian r...
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| Published in: | Scientific reports 2023-01, Vol.13 (1), p.1721-1721, Article 1721 |
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| description | The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10
−4
) as might its ER+ subtype (FDR = 1.51 × 10
−4
). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10
−6
). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10
−3
) as could total testosterone (TT) (FDR = 5.81 × 10
−3
). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10
−6
) as could TT (FDR = 5.55 × 10
−4
). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density. |
| doi_str_mv | 10.1038/s41598-023-28899-0 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_ffba0cd4a70547358838f712334f9cc4</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_ffba0cd4a70547358838f712334f9cc4</doaj_id><sourcerecordid>2771636300</sourcerecordid><originalsourceid>FETCH-LOGICAL-c540t-dd7c03a5c171c818be37c7571a5d715074c33c786ba639deadf6a70c9c1faaab3</originalsourceid><addsrcrecordid>eNp9kk1v1DAQhiMEolXpH-CALHHhEvBHHNsXJFTxUamIC5ytiT1ZvErsYmepll-Pd1NKywFfbM08fj3jeZvmOaOvGRX6TemYNLqlXLRca2Na-qg55bSTLRecP753PmnOS9nSuiQ3HTNPmxPRK04NZaeN_YzR4xQgkgzRpzn8giWkSCDCtC9YSBoJlJJcOMYLGXC5QYxkyAhlIQ6iw1xxT4YUkcwhYoaJeIwlLPtnzZMRpoLnt_tZ8-3D-68Xn9qrLx8vL95dtU52dGm9V44KkI4p5jTTAwrllFQMpFdMUtU5IZzS_QC9MB7Bjz0o6oxjIwAM4qy5XHV9gq29zmGGvLcJgj0GUt5YyEtwE9pxHIA639X7slNCai30qBgXohuNc13VertqXe-GGb3DuNSOHog-zMTw3W7ST2vqIJQ5CLy6Fcjpxw7LYudQHE4TREy7YrlSrBe9oLSiL_9Bt2mX69-vFDOmFlkpvlIup1IyjnfFMGoPdrCrHWy1gz3awR6kX9xv4-7Kn-FXQKxAqam4wfz37f_I_gYKqcH5</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2771199054</pqid></control><display><type>article</type><title>Mendelian randomization analyses of associations between breast cancer and bone mineral density</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Wu, Hong ; Wang, Hui ; Liu, Di ; Liu, Zhibing ; Zhang, Weiming</creator><creatorcontrib>Wu, Hong ; Wang, Hui ; Liu, Di ; Liu, Zhibing ; Zhang, Weiming</creatorcontrib><description>The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10
−4
) as might its ER+ subtype (FDR = 1.51 × 10
−4
). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10
−6
). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10
−3
) as could total testosterone (TT) (FDR = 5.81 × 10
−3
). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10
−6
) as could TT (FDR = 5.55 × 10
−4
). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-023-28899-0</identifier><identifier>PMID: 36720901</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67 ; 631/67/69 ; Bone cancer ; Bone density ; Bone Density - genetics ; Bone mineral density ; Breast cancer ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Humanities and Social Sciences ; Mendelian Randomization Analysis ; multidisciplinary ; Neoplasms ; Risk factors ; Science ; Science (multidisciplinary) ; Statistical analysis ; Testosterone</subject><ispartof>Scientific reports, 2023-01, Vol.13 (1), p.1721-1721, Article 1721</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-dd7c03a5c171c818be37c7571a5d715074c33c786ba639deadf6a70c9c1faaab3</citedby><cites>FETCH-LOGICAL-c540t-dd7c03a5c171c818be37c7571a5d715074c33c786ba639deadf6a70c9c1faaab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2771199054/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2771199054?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36720901$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Hong</creatorcontrib><creatorcontrib>Wang, Hui</creatorcontrib><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Liu, Zhibing</creatorcontrib><creatorcontrib>Zhang, Weiming</creatorcontrib><title>Mendelian randomization analyses of associations between breast cancer and bone mineral density</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10
−4
) as might its ER+ subtype (FDR = 1.51 × 10
−4
). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10
−6
). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10
−3
) as could total testosterone (TT) (FDR = 5.81 × 10
−3
). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10
−6
) as could TT (FDR = 5.55 × 10
−4
). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.</description><subject>631/67</subject><subject>631/67/69</subject><subject>Bone cancer</subject><subject>Bone density</subject><subject>Bone Density - genetics</subject><subject>Bone mineral density</subject><subject>Breast cancer</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humanities and Social Sciences</subject><subject>Mendelian Randomization Analysis</subject><subject>multidisciplinary</subject><subject>Neoplasms</subject><subject>Risk factors</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Statistical analysis</subject><subject>Testosterone</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk1v1DAQhiMEolXpH-CALHHhEvBHHNsXJFTxUamIC5ytiT1ZvErsYmepll-Pd1NKywFfbM08fj3jeZvmOaOvGRX6TemYNLqlXLRca2Na-qg55bSTLRecP753PmnOS9nSuiQ3HTNPmxPRK04NZaeN_YzR4xQgkgzRpzn8giWkSCDCtC9YSBoJlJJcOMYLGXC5QYxkyAhlIQ6iw1xxT4YUkcwhYoaJeIwlLPtnzZMRpoLnt_tZ8-3D-68Xn9qrLx8vL95dtU52dGm9V44KkI4p5jTTAwrllFQMpFdMUtU5IZzS_QC9MB7Bjz0o6oxjIwAM4qy5XHV9gq29zmGGvLcJgj0GUt5YyEtwE9pxHIA639X7slNCai30qBgXohuNc13VertqXe-GGb3DuNSOHog-zMTw3W7ST2vqIJQ5CLy6Fcjpxw7LYudQHE4TREy7YrlSrBe9oLSiL_9Bt2mX69-vFDOmFlkpvlIup1IyjnfFMGoPdrCrHWy1gz3awR6kX9xv4-7Kn-FXQKxAqam4wfz37f_I_gYKqcH5</recordid><startdate>20230131</startdate><enddate>20230131</enddate><creator>Wu, Hong</creator><creator>Wang, Hui</creator><creator>Liu, Di</creator><creator>Liu, Zhibing</creator><creator>Zhang, Weiming</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20230131</creationdate><title>Mendelian randomization analyses of associations between breast cancer and bone mineral density</title><author>Wu, Hong ; Wang, Hui ; Liu, Di ; Liu, Zhibing ; Zhang, Weiming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-dd7c03a5c171c818be37c7571a5d715074c33c786ba639deadf6a70c9c1faaab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>631/67</topic><topic>631/67/69</topic><topic>Bone cancer</topic><topic>Bone density</topic><topic>Bone Density - genetics</topic><topic>Bone mineral density</topic><topic>Breast cancer</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Humanities and Social Sciences</topic><topic>Mendelian Randomization Analysis</topic><topic>multidisciplinary</topic><topic>Neoplasms</topic><topic>Risk factors</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Statistical analysis</topic><topic>Testosterone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Hong</creatorcontrib><creatorcontrib>Wang, Hui</creatorcontrib><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Liu, Zhibing</creatorcontrib><creatorcontrib>Zhang, Weiming</creatorcontrib><collection>SpringerOpen</collection><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Hong</au><au>Wang, Hui</au><au>Liu, Di</au><au>Liu, Zhibing</au><au>Zhang, Weiming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mendelian randomization analyses of associations between breast cancer and bone mineral density</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2023-01-31</date><risdate>2023</risdate><volume>13</volume><issue>1</issue><spage>1721</spage><epage>1721</epage><pages>1721-1721</pages><artnum>1721</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10
−4
) as might its ER+ subtype (FDR = 1.51 × 10
−4
). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10
−6
). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10
−3
) as could total testosterone (TT) (FDR = 5.81 × 10
−3
). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10
−6
) as could TT (FDR = 5.55 × 10
−4
). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36720901</pmid><doi>10.1038/s41598-023-28899-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/67 631/67/69 Bone cancer Bone density Bone Density - genetics Bone mineral density Breast cancer Genome-wide association studies Genome-Wide Association Study Genomes Humanities and Social Sciences Mendelian Randomization Analysis multidisciplinary Neoplasms Risk factors Science Science (multidisciplinary) Statistical analysis Testosterone |
| title | Mendelian randomization analyses of associations between breast cancer and bone mineral density |
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