meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11 | Human Molecular Genetics

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Haiman</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Christopher A. Haiman <span class="info-card-footnote"><span class="xrefLink" id="jumplink-cor1"></span><a href="javascript:;" reveal-id="cor1" data-open="cor1" class="link link-ref link-reveal xref-default">*</a></span> </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">6</span><div class="addr-line">Department of Preventive Medicine</div> and</div> </div> <div class="info-author-correspondence"> <div content-id="cor1"><span class="label title-label">*</span>To whom correspondence should be addressed at: Mayo Clinic, 200 First St SW, Charlton 6-239, Rochester, MN 55905, USA. Tel: +1 5072849977; Fax: +<div class="fax">1 5072662478</div>; Email: <a href="mailto:vachon.celine@mayo.edu" target="_blank">vachon.celine@mayo.edu</a> (C.M.V.); Harlyne Norris Research Tower, 1450 Biggy Street, Room 1504, Los Angeles, CA 90033, USA. 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Vachon</button><span class='delimiter'></span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Celine M. Vachon <span class="info-card-footnote"><span class="xrefLink" id="jumplink-cor1"></span><a href="javascript:;" reveal-id="cor1" data-open="cor1" class="link link-ref link-reveal xref-default">*</a></span> </div> </div> <div class="info-card-affilitation"> <div class="aff"><span class="label title-label">3</span><div class="addr-line">Department of Health Sciences Research</div>,</div> </div> <div class="info-author-correspondence"> <div content-id="cor1"><span class="label title-label">*</span>To whom correspondence should be addressed at: Mayo Clinic, 200 First St SW, Charlton 6-239, Rochester, MN 55905, USA. Tel: +1 5072849977; Fax: +<div class="fax">1 5072662478</div>; Email: <a href="mailto:vachon.celine@mayo.edu" target="_blank">vachon.celine@mayo.edu</a> (C.M.V.); Harlyne Norris Research Tower, 1450 Biggy Street, Room 1504, Los Angeles, CA 90033, USA. Email: <a href="mailto:christopher.haiman@med.usc.edu" target="_blank">christopher.haiman@med.usc.edu</a> (C.A.H.)</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/hmg/search-results?f_Authors=Celine+M.+Vachon" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-pubmed"> <a href="http://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=Vachon C">PubMed</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Vachon Celine M.%22">Google Scholar</a> </div> </div> </span> </span> </div> </div> </div> </div> <div class="pub-history-wrap clearfix js-history-dropdown-wrap"> <div class="pub-history-row clearfix"> <div class="ww-citation-primary"><em>Human Molecular Genetics</em>, Volume 21, Issue 24, 15 December 2012, Pages 5373–5384, <a href='https://doi.org/10.1093/hmg/dds381'>https://doi.org/10.1093/hmg/dds381</a></div> </div> <div class="pub-history-row clearfix"> <div class="ww-citation-date-wrap"> <div class="citation-label">Published:</div> <div class="citation-date">13 September 2012</div> </div> <a href="javascript:;" class="history-label js-history-dropdown-trigger st-article-history at-ArticleHistory"> <span>Article history</span><i class="icon-general-arrow-filled-down arrow-icon"></i> </a> </div> <div class="ww-history js-history-entries-wrap at-history-entries-wrap"> <div class="history-entry at-history-entry"> <div class="wi-state">Received:</div> <div class="wi-date">26 March 2012</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Accepted:</div> <div class="wi-date">06 September 2012</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Published:</div> <div class="wi-date">13 September 2012</div> </div> </div> </div> </div> </div> <script> $(document).ready(function () { $('.article-top-widget').on('click', '.ati-toggle-trigger', function () { $(this).find('.icon-general-add, .icon-minus').toggleClass('icon-minus icon-general-add'); $(this).siblings('.ati-toggle-content').toggleClass('hide'); }); // In Chrome, an anchor tag with target="_blank" and a "mailto:" href opens a new tab/window as well as the email client // I suspect this behavior will be corrected in the future // Remove the target="_blank" $('ul.wi-affiliationList').find('a[href^="mailto:"]').each(function () { $(this).removeAttr('target'); }); }); </script> </div> <div class="widget widget-ArticleLinks widget-instance-OUP_Article_Links_Widget"> </div> <div class="article-body js-content-body"> <div class="toolbar-wrap js-toolbar-wrap"> <div class="toolbar-inner-wrap"> <ul id="Toolbar" role="navigation"> <li class="toolbar-item item-with-dropdown item-views"> <a class="at-views-dropdown drop-trigger" href="javascript:;" data-dropdown="FilterDrop" aria-haspopup="true"> <i class="icon-menu_views"></i> <div class="toolbar-label"> <div class="toolbar-text">Views</div> <i class="icon-general-arrow-filled-down arrow-icon"></i> </div> </a> <ul id="ViewsDrop" class="f-dropdown js-dropdown-content" data-dropdown-content aria-label="submenu"> <div class="arrow-up"></div> <li class="article-content-filter js-article-content-filter" data-content-filter="article-content"> <a href="javascript:;"><span>Article contents</span></a> </li> <li class="at-figures-tables article-content-filter js-article-content-filter" data-content-filter="figures-tables"> <a href="javascript:;"><span>Figures & tables</span></a> </li> <li class="article-content-filter js-article-content-filter" data-content-filter="video"> <a href="javascript:;"><span>Video</span></a> </li> <li class="article-content-filter js-article-content-filter" data-content-filter="audio"> <a href="javascript:;"><span>Audio</span></a> </li> <li class="article-content-filter js-article-content-filter" data-content-filter="supplementary-data"> <a href="javascript:;"><span>Supplementary Data</span></a> </li> </ul> </li> <li class="toolbar-item item-cite js-item-cite"> <div class="widget widget-ToolboxGetCitation widget-instance-OUP_Get_Citation"> <a href="#" class="js-cite-button at-CiteButton" data-reveal-id="getCitation" data-reveal> <i class="icon-read-more"></i> <span>Cite</span> </a> <div id="getCitation" class="reveal-modal js-citation-modal" data-reveal> <h3 class="modal-title">Cite</h3> <div class="oxford-citation-text"> <p>Afshan Siddiq, Fergus J. 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Vachon, A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11, <em>Human Molecular Genetics</em>, Volume 21, Issue 24, 15 December 2012, Pages 5373–5384, <a href="https://doi.org/10.1093/hmg/dds381">https://doi.org/10.1093/hmg/dds381</a></p> </div> <div class="citation-download-wrap"> <form action="/Citation/Download" method="get" id="citationModal"> <input type="hidden" name="resourceId" value="665552" /> <input type="hidden" name="resourceType" value="3" /> <label for="selectFormat" class="hide js-citation-format-label">Select Format</label> <select required name="citationFormat" class="citation-download-format js-citation-format" id="selectFormat"> <option selected disabled >Select format</option> <option value="0" >.ris (Mendeley, Papers, Zotero)</option> <option value="1" >.enw (EndNote)</option> <option value="2" >.bibtex (BibTex)</option> <option value="3" >.txt (Medlars, RefWorks)</option> </select> 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To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed <em>in silico</em> replication of 86 SNPs at <em>P</em> ≤ 1 × 10<sup>-5</sup> in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; <em>P</em> = 1.1 × 10<sup>−8</sup>) but showed a weaker association with overall breast cancer (OR = 1.08, <em>P</em> = 1.3 × 10<sup>–6</sup>) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, <em>P</em> = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; <em>P</em> = 1.1 × 10<sup>−9</sup>), and with both ER-positive (OR = 1.09; <em>P</em> = 1.5 × 10<sup>−5</sup>) and ER-negative (OR = 1.16, <em>P</em> = 2.5 × 10<sup>−7</sup>) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.</p></section> <div class="article-metadata-panel clearfix at-ArticleMetadata"></div>  <div class="widget widget-ArticlePubStateInfo widget-instance-OUP_ArticlePubStateInfo"> </div> <div class="article-metadata-standalone-panel clearfix"></div> <div class="copyright copyright-statement">© The Author 2012. Published by Oxford University Press. All rights reserved. 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<td>August 2022</td> <td>38</td> </tr> <tr> <td>September 2022</td> <td>782</td> </tr> <tr> <td>October 2022</td> <td>730</td> </tr> <tr> <td>November 2022</td> <td>343</td> </tr> <tr> <td>December 2022</td> <td>454</td> </tr> <tr> <td>January 2023</td> <td>349</td> </tr> <tr> <td>February 2023</td> <td>47</td> </tr> <tr> <td>March 2023</td> <td>105</td> </tr> <tr> <td>April 2023</td> <td>583</td> </tr> <tr> <td>May 2023</td> <td>115</td> </tr> <tr> <td>June 2023</td> <td>44</td> </tr> <tr> <td>July 2023</td> <td>60</td> </tr> <tr> <td>August 2023</td> <td>30</td> </tr> <tr> <td>September 2023</td> <td>37</td> </tr> <tr> <td>October 2023</td> <td>37</td> </tr> <tr> <td>November 2023</td> <td>57</td> </tr> <tr> <td>December 2023</td> <td>61</td> </tr> <tr> <td>January 2024</td> <td>59</td> </tr> <tr> <td>February 2024</td> <td>81</td> </tr> <tr> <td>March 2024</td> <td>101</td> </tr> <tr> <td>April 2024</td> <td>97</td> </tr> <tr> <td>May 2024</td> <td>85</td> </tr> <tr> <td>June 2024</td> <td>39</td> </tr> <tr> <td>July 2024</td> <td>42</td> </tr> <tr> <td>August 2024</td> <td>30</td> </tr> <tr> <td>September 2024</td> <td>32</td> </tr> <tr> <td>October 2024</td> <td>16</td> </tr> <tr> <td>November 2024</td> <td>11</td> </tr> </tbody> </table> </div> </div> <div class="artmet-stats-wrap clearfix"> <div class="artmet-item artmet-citations hide"> <div class="widget-title-2 artmet-widget-title-2">Citations</div> <div class="artmet-badges-wrap artmet-dimensions"> <div class="widget widget-DimensionsBadge widget-instance-ArticleLevelMetrics_DimensionsBadgeDetails"> <span class="__dimensions_badge_embed__" data-doi="10.1093/hmg/dds381" data-legend="always" data-style="" data-hide-zero-citations="false"></span> <script async src="https://badge.dimensions.ai/badge.js" charset="utf-8"></script> </div> <span class="artmet-dimensions-text">Powered by Dimensions</span> </div> <div class="artmet-wos"> <span class="artmet-number"> <a 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meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11 | Human Molecular Genetics | Oxford Academic