{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:06:15Z","timestamp":1761717975318,"version":"build-2065373602"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,7,26]],"date-time":"2005-07-26T00:00:00Z","timestamp":1122336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2005,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Factors that are predictive of carrying <jats:italic>BRCA<\/jats:italic>1 and <jats:italic>BRCA<\/jats:italic>2 germline mutations in patients with breast carcinoma are awaited widely. The genetically homogeneous Sardinian population may be useful for defining the role of such genetic alterations further through a clinical evaluation program.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>One hundred two of 659 patients with breast carcinoma (15.5%) who were collected consecutively had a family history of breast carcinoma and were screened for <jats:italic>BRCA<\/jats:italic>1\/2 mutations by denaturing high\u2010performance liquid chromatography and DNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Three deleterious germline <jats:italic>BRCA<\/jats:italic>1\/2 mutations were detected in 15 of 102 families (14.7%), including 13 families (86.7%) with <jats:italic>BRCA<\/jats:italic>2 mutations and 2 families (13.3%) with <jats:italic>BRCA<\/jats:italic>1 mutations. A single variant, BRCA2\u20108765delAG, was the most recurrent mutation in the series and was found in 12 of 102 families (11.8%) and in 18 of 657 patients (2.7%). The average age at diagnosis was significantly younger in families with <jats:italic>BRCA<\/jats:italic>1\/2 mutations (48.6 yrs) compared with the age of patients who had no detectable mutation (52.9 yrs; <jats:italic>P<\/jats:italic> = 0.039). Moreover, <jats:italic>BRCA<\/jats:italic>1\/2 mutations were found at a significantly higher rate in families who had at least 1 member with ovarian carcinoma or male breast carcinoma (5 of 12 families; 41.7%) than in families without such an association (10 of 90 families; 11.1%; <jats:italic>P<\/jats:italic> = 0.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p><jats:italic>BRCA<\/jats:italic>2 mutations were approximately 6 times more prevalent than <jats:italic>BRCA<\/jats:italic>1 mutations. A diagnosis of breast carcinoma before age 50 years, ovarian carcinoma, male breast carcinoma, and 3 affected generations all were associated significantly with <jats:italic>BRCA<\/jats:italic>1\/2 mutations. Although the current findings provided further support for the hypothesis that additional breast carcinoma susceptibility genes remain to be identified, such indicators of the presence of <jats:italic>BRCA<\/jats:italic>1\/2 mutations may be useful in counseling patients about undergoing genetic testing. Cancer 2005. \u00a9 2005 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.21298","type":"journal-article","created":{"date-parts":[[2005,7,26]],"date-time":"2005-07-26T15:27:07Z","timestamp":1122391627000},"page":"1172-1179","source":"Crossref","is-referenced-by-count":22,"title":["Spectrum and prevalence of <i>BRCA<\/i>1 and <i>BRCA<\/i>2 germline mutations in Sardinian patients with breast carcinoma through hospital\u2010based screening"],"prefix":"10.1002","volume":"104","author":[{"given":"Grazia","family":"Palomba","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Pisano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cossu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Budroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria F.","family":"Dedola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Farris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Contu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Baldinu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Tanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Palmieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,7,26]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960601)77:11<2318::AID-CNCR21>3.0.CO;2-Z"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91578-4"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/318181"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.15.1310"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200008)16:2<123::AID-HUMU4>3.0.CO;2-Y"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-185"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705153362001"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-392"},{"key":"e_1_2_6_10_2","first-page":"3663","article-title":"High prevalence of the 999del5 mutation in Icelandic breast and ovarian cancer patients","volume":"56","author":"Johannesdottir G","year":"1996","journal-title":"Cancer Res."},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-117"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.13.2309"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201091"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.16.1215"},{"key":"e_1_2_6_15_2","first-page":"1041","article-title":"A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families","volume":"60","author":"Peelen T","year":"1997","journal-title":"Am J Hum Genet."},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-341"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00244-1"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08740.x"},{"key":"e_1_2_6_19_2","first-page":"1239","article-title":"Frequently occurring germ\u2010line mutations of the BRCA1 gene in ovarian cancer families from Russia","volume":"60","author":"Gayther SA","year":"1997","journal-title":"Am J Hum Genet."},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/302922"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-14"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1196-1179"},{"key":"e_1_2_6_24_2","first-page":"1013","article-title":"Population genetics of BRCA1 and BRCA2","volume":"60","author":"Szabo CI","year":"1997","journal-title":"Am J Hum Genet."},{"key":"e_1_2_6_25_2","unstructured":"National Human Genome Research Institute. 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