{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:32:03Z","timestamp":1790951523554,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017008","name":"Cancer Research UK Manchester Centre","doi-asserted-by":"publisher","award":["C147\/A18083"],"award-info":[{"award-number":["C147\/A18083"]}],"id":[{"id":"10.13039\/501100017008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017008","name":"Cancer Research UK Manchester Centre","doi-asserted-by":"publisher","award":["C147\/A25254"],"award-info":[{"award-number":["C147\/A25254"]}],"id":[{"id":"10.13039\/501100017008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NIHR300650"],"award-info":[{"award-number":["NIHR300650"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>BRIP1<\/jats:italic>\n                    is a moderate susceptibility epithelial ovarian cancer (EOC) gene. Having identified the\n                    <jats:italic>BRIP1<\/jats:italic>\n                    c.1045G&gt;C missense variant in a number of families with EOC, we aimed to investigate the frequency of this and\n                    <jats:italic>BRIP1<\/jats:italic>\n                    .2392C&gt;T pathogenic variant in patients with breast cancer (BC) and\/or EOC. A case\u2010control study of 3767 cases and 2043 controls was undertaken investigating the presence of these variants using Sanger sequencing and gene panel data. Individuals with BC and\/or EOC were grouped by family history.\n                    <jats:italic>BRIP1<\/jats:italic>\n                    c.1045G&gt;C was associated with increased risk of BC\/EOC (OR\u00a0=\u00a037.7; 95% CI 5.3\u2013444.2;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u20090.0001). The risk was highest for women with EOC (OR\u00a0=\u00a0140.8; 95% CI 23.5\u20131723.0;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u20090.0001) and lower for BC (OR\u00a0=\u00a011.1; 95% CI 1.2\u2013106.5;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u20090.1588).\n                    <jats:italic>BRIP1<\/jats:italic>\n                    c.2392C&gt;T was associated with smaller risks for BC\/EOC (OR\u00a0=\u00a05.4; 95%CI 2.4\u201312.7;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u20090.0003), EOC (OR\u00a0=\u00a05.9; 95% CI 1.3\u201323.0;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u20090.0550) and BC (OR\u00a0=\u00a05.3; 95%CI 2.3\u201312.9;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u20090.0009). Our study highlights the importance of\n                    <jats:italic>BRIP1<\/jats:italic>\n                    as an EOC susceptibility gene, especially in familial EOC. The variant\n                    <jats:italic>BRIP1<\/jats:italic>\n                    c.1045G&gt;C, rs149364097, is of particular interest as its dominant\u2010negative effect may confer a higher risk of EOC than that of the previously reported\n                    <jats:italic>BRIP1<\/jats:italic>\n                    c.2392C&gt;T nonsense variant. Dominant\u2010negative missense variants may confer higher risks than their loss\u2010of\u2010function counterparts.\n                  <\/jats:p>","DOI":"10.1111\/cge.14068","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T05:33:17Z","timestamp":1632893597000},"page":"48-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Dominant\u2010negative pathogenic variant\n                    <scp>BRIP1<\/scp>\n                    c.\n                    <scp>1045G<\/scp>\n                    &gt;C is a high\u2010risk allele for non\u2010mucinous epithelial ovarian cancer: A case\u2010control study"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-0645","authenticated-orcid":false,"given":"Nicola","family":"Flaum","sequence":"first","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8618-2332","authenticated-orcid":false,"given":"Elke M.","family":"van Veen","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Amico","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6098-9995","authenticated-orcid":false,"given":"William G.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J.","family":"Crosbie","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Edmondson","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3184-0817","authenticated-orcid":false,"given":"Miriam J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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