{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:25:12Z","timestamp":1790252712539,"version":"4.1.0"},"reference-count":26,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recent candidate and genome-wide association studies have identified variants altering susceptibility to breast cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To establish the relevance of these variants to breast cancer risk in familial breast cancer cases both with and without <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> (<jats:italic>BRCA1\/2<\/jats:italic>) mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A cohort of unrelated individuals with breast cancer due to the presence of either <jats:italic>BRCA1<\/jats:italic> (121) or <jats:italic>BRCA2<\/jats:italic> mutations (109) and individuals with familial breast cancer not due to <jats:italic>BRCA1\/2<\/jats:italic> mutations (722) were genotyped using Taqman SNP Genotyping Assays. Allele frequencies were compared with an ethnically and gender-matched group (436).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A synonymous variant (Ser51) in <jats:italic>TOX3<\/jats:italic> (previously <jats:italic>TNRC9)<\/jats:italic> was associated with an increased risk of breast cancer (OR=1.82, p&lt;0.001) in <jats:italic>BRCA2<\/jats:italic> mutation carriers. The associations for <jats:italic>FGFR2<\/jats:italic> (OR=1.20, p=0.046), <jats:italic>TOX3<\/jats:italic> (OR=1.5, p&lt;0.001), <jats:italic>MAP3K1<\/jats:italic> (OR=1.26 p=0.03), <jats:italic>CASP8<\/jats:italic> (OR=0.73 p=0.02) and the chromosome 8-associated SNP (OR=1.31, p=0.004) were replicated in individuals without <jats:italic>BRCA1\/2<\/jats:italic> mutations. In addition, homozygote carriers of <jats:italic>MAP3K1<\/jats:italic> variants were shown to have a significantly lower Manchester Score (mean 13.8\u201317.6, p=0.003), whereas individuals carrying one or two copies of the <jats:italic>FGFR2<\/jats:italic> variant had a higher Manchester Score (mean 17.5\u201317.9, p=0.01).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study confirms that susceptibility variants in <jats:italic>FGFR2<\/jats:italic>, <jats:italic>TOX3<\/jats:italic> and <jats:italic>MAP3K1<\/jats:italic> and on chromosome 8q are all associated with increased risk of cancer in individuals with a family history of breast cancer, whereas <jats:italic>CASP8<\/jats:italic> is protective in this context. The level of risk is dependent on the strength of the family history and the presence of a <jats:italic>BRCA1\/2<\/jats:italic> mutation and contributes to the understanding of the use of these variants in clinical risk prediction.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.067256","type":"journal-article","created":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T20:19:37Z","timestamp":1247861977000},"page":"126-131","source":"Crossref","is-referenced-by-count":32,"title":["Breast cancer susceptibility variants alter risks in familial disease"],"prefix":"10.1136","volume":"47","author":[{"given":"Ay\u015fe","family":"Latif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen D","family":"Hadfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Shenton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Lalloo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme C M","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Gareth","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2009,7,16]]},"reference":[{"key":"2025101715281098000_47.2.126.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.53"},{"key":"2025101715281098000_47.2.126.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng853"},{"key":"2025101715281098000_47.2.126.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.9.081307.164339"},{"key":"2025101715281098000_47.2.126.4","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj090"},{"key":"2025101715281098000_47.2.126.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng1981"},{"key":"2025101715281098000_47.2.126.6","unstructured":"Palanca Suela S Esteban Carde\u00f1osa E Barrag\u00e1n Gonz\u00e1lez E de Juan Jim\u00e9nez I Chirivella Gonz\u00e1lez I Segura Huerta A Guill\u00e9n Ponce C Mart\u00ednez de Due\u00f1as E Montalar Salcedo J Castel S\u00e1nchez V Bolufer Gilabert P , On Behalf of the Group for Assessment of Hereditary Cancer of Valencia Community. CASP8 D302H polymorphism delays the age of onset of breast cancer in BRCA1 and BRCA2 carriers. Breast Cancer Res Treat 12 February 2009."},{"key":"2025101715281098000_47.2.126.7","first-page":"39","article-title":"Recent advances in the genetics of susceptibility to and treatment of breast cancer","volume":"5","author":"Newman","year":"2008","journal-title":"Adv Breast Cancer"},{"key":"2025101715281098000_47.2.126.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature05887"},{"key":"2025101715281098000_47.2.126.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng2075"},{"key":"2025101715281098000_47.2.126.10","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1793"},{"key":"2025101715281098000_47.2.126.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000054"},{"key":"2025101715281098000_47.2.126.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800441105"},{"key":"2025101715281098000_47.2.126.13","doi-asserted-by":"publisher","DOI":"10.1038\/ng2064"},{"key":"2025101715281098000_47.2.126.14","doi-asserted-by":"publisher","DOI":"10.1038\/ng.131"},{"key":"2025101715281098000_47.2.126.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.02.008"},{"key":"2025101715281098000_47.2.126.16","unstructured":"NICE clinical guideline 41. Familial breast cancer. The classification and care of women at risk of familial breast cancer in primary, secondary and tertiary care. 2006."},{"key":"2025101715281098000_47.2.126.17","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.031989"},{"key":"2025101715281098000_47.2.126.18","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.056556"},{"key":"2025101715281098000_47.2.126.19","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.017996"},{"key":"2025101715281098000_47.2.126.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)10109-4"},{"key":"2025101715281098000_47.2.126.21","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.09.023"},{"key":"2025101715281098000_47.2.126.22","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-0018"},{"key":"2025101715281098000_47.2.126.23","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2213"},{"key":"2025101715281098000_47.2.126.24","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn247"},{"key":"2025101715281098000_47.2.126.25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa0708739"},{"key":"2025101715281098000_47.2.126.26","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn180"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2009.067256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T22:28:18Z","timestamp":1760740098000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2009.067256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,16]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2010,2,9]]},"published-print":{"date-parts":[[2010,2]]}},"alternative-id":["10.1136\/jmg.2009.067256"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2009.067256","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,16]]}}}