{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T13:53:38Z","timestamp":1761486818101,"version":"build-2065373602"},"reference-count":36,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2001,3,27]]},"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>A small fraction of breast cancer is the result of germline mutations in the<jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic>cancer susceptibility genes. Mutation carriers frequently have a positive family history of breast and ovarian cancer, are often diagnosed at a young age, and may have a higher incidence of double or multiple primary breast tumours than breast cancer patients in general.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>To estimate the prevalence and spectrum of <jats:italic>BRCA1 <\/jats:italic>and<jats:italic>BRCA2<\/jats:italic> mutations in young Danish patients affected with bilateral or multifocal breast cancer and to determine the relationship of mutation status to family history of cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUBJECTS<\/jats:title>\n                  <jats:p>From the files of the Danish Breast Cancer Cooperative Group (DBCG), we selected 119 breast cancer patients diagnosed before the age of 46 years with either bilateral (n=59) or multifocal (n=61) disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec sec-type=\"methods\">\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>DNA from the subjects was screened for <jats:italic>BRCA1<\/jats:italic> and<jats:italic>BRCA2<\/jats:italic> mutations using single strand conformation analysis (SSCA) and the protein truncation test (PTT). Observed and expected cancer incidence in first degree relatives of the patients was estimated using data from the Danish Cancer Registry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Twenty four mutation carriers were identified (20%), of whom 13 had a<jats:italic>BRCA1<\/jats:italic> mutation and 11 carried a<jats:italic>BRCA2 <\/jats:italic>mutation. Two mutations in<jats:italic>BRCA1 <\/jats:italic>were found repeatedly in the material and accounted for seven of the 24 (29%) mutation carriers. The mutation frequency was about equal in patients with bilateral (22%) and multifocal breast cancer (18%). The incidence of breast and ovarian cancer was greatly increased in first degree relatives of<jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic>mutation carriers, but to a much lesser degree in relatives of non-carriers. An increased risk of cancer was also noted in brothers of non-carriers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>A relatively broad spectrum of germline mutations was observed in<jats:italic>BRCA1 <\/jats:italic>and <jats:italic>BRCA2<\/jats:italic>and most of the mutations are present in other populations. Our results indicate that a diagnosis of bilateral and multifocal breast cancer is predictive of <jats:italic>BRCA1<\/jats:italic> and<jats:italic>BRCA2<\/jats:italic> mutation status, particularly when combined with information on the patients' age at diagnosis and family history of breast\/ovarian cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.38.6.361","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:38:40Z","timestamp":1027751920000},"page":"361-368","source":"Crossref","is-referenced-by-count":38,"title":["<i>BRCA1<\/i> and<i>BRCA2<\/i> mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age"],"prefix":"10.1136","volume":"38","author":[{"given":"J T","family":"Bergthorsson","sequence":"first","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Ejlertsen","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J H","family":"Olsen","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Borg","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K V","family":"Nielsen","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R B","family":"Barkardottir","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Klausen","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H T","family":"Mouridsen","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Winther","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Fenger","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Niebuhr","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T L","family":"Harboe","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Niebuhr","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark, \n\nbLaboratory of Cell Biology, Department of Pathology, University Hospital of Iceland, Landspitalinn, Building 14, 101 Reykjavik, Iceland, \n\ncDepartment of Oncology, The Finsen Centre, Rigshospitalet, Building 5-01-2, Blegdamsvej 9, 2100 Copenhagen, Denmark, \n\ndDivision for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2001,6,1]]},"reference":[{"key":"2025101712454849000_38.6.361.1","first-page":"1013","article-title":"Population genetics of BRCA1 and BRCA2.","volume":"60","author":"Szabo","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2025101712454849000_38.6.361.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7545954"},{"key":"2025101712454849000_38.6.361.3","doi-asserted-by":"publisher","DOI":"10.1038\/378789a0"},{"key":"2025101712454849000_38.6.361.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01930-7"},{"key":"2025101712454849000_38.6.361.5","first-page":"1222","article-title":"Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations.","volume":"57","author":"Tirkkonen","year":"1997","journal-title":"Cancer Res"},{"key":"2025101712454849000_38.6.361.6","doi-asserted-by":"publisher","DOI":"10.1086\/301749"},{"key":"2025101712454849000_38.6.361.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-123"},{"key":"2025101712454849000_38.6.361.8","first-page":"5360","article-title":"Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas.","volume":"56","author":"Goggins","year":"1996","journal-title":"Cancer Res"},{"key":"2025101712454849000_38.6.361.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)10109-4"},{"key":"2025101712454849000_38.6.361.10","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-309"},{"key":"2025101712454849000_38.6.361.11","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-428"},{"key":"2025101712454849000_38.6.361.12","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-103"},{"key":"2025101712454849000_38.6.361.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705153362001"},{"key":"2025101712454849000_38.6.361.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)03300-5"},{"key":"2025101712454849000_38.6.361.15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690106"},{"key":"2025101712454849000_38.6.361.16","first-page":"234","article-title":"Multicentricity and bilaterality in invasive breast carcinoma.","volume":"91","author":"Lesser","year":"1982","journal-title":"Surgery"},{"key":"2025101712454849000_38.6.361.17","first-page":"1068","article-title":"Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer.","volume":"60","author":"Hakansson","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2025101712454849000_38.6.361.18","unstructured":"Rothman KJ Boice JD (1979) Epidemiologic analysis with a programmable calculator. (Government Printing Office, Washington DC)."},{"key":"2025101712454849000_38.6.361.19","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.9.1289"},{"key":"2025101712454849000_38.6.361.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13595"},{"key":"2025101712454849000_38.6.361.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-238"},{"key":"2025101712454849000_38.6.361.22","first-page":"1021","article-title":"BRCA1 sequence variations in 160 individuals referred to a breast\/ovarian family cancer clinic. Institut Curie Breast Cancer Group.","volume":"60","author":"Stoppa-Lyonnet","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2025101712454849000_38.6.361.23","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201861"},{"key":"2025101712454849000_38.6.361.24","doi-asserted-by":"publisher","DOI":"10.1038\/ng1296-430"},{"key":"2025101712454849000_38.6.361.25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.6.835"},{"key":"2025101712454849000_38.6.361.26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201360"},{"key":"2025101712454849000_38.6.361.27","doi-asserted-by":"publisher","DOI":"10.1038\/386772a0"},{"key":"2025101712454849000_38.6.361.28","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-253"},{"key":"2025101712454849000_38.6.361.29","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1038\/bjc.1998.701","article-title":"BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1.","volume":"78","author":"Lancaster","year":"1998","journal-title":"Br J Cancer"},{"key":"2025101712454849000_38.6.361.30","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-341"},{"key":"2025101712454849000_38.6.361.31","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.12.922"},{"key":"2025101712454849000_38.6.361.32","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.11.943"},{"key":"2025101712454849000_38.6.361.33","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200371"},{"key":"2025101712454849000_38.6.361.34","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1093\/ajcp\/99.3.238","article-title":"Multicentricity in breast cancer. A study of 366 cases.","volume":"99","author":"Anastassiades","year":"1993","journal-title":"Am J Clin Pathol"},{"key":"2025101712454849000_38.6.361.35","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(81)90288-9"},{"key":"2025101712454849000_38.6.361.36","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19850201)55:3<643::AID-CNCR2820550328>3.0.CO;2-L"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.38.6.361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:45:56Z","timestamp":1760730356000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.38.6.361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6,1]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2001,6,1]]},"published-print":{"date-parts":[[2001,6,1]]}},"alternative-id":["10.1136\/jmg.38.6.361"],"URL":"https:\/\/doi.org\/10.1136\/jmg.38.6.361","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[2001,6,1]]}}}