{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:14:23Z","timestamp":1791850463269,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,9,22]],"date-time":"2006-09-22T00:00:00Z","timestamp":1158883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2006,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Among Asian countries, Pakistan has the highest rates of breast and ovarian cancer. To assess the contribution of the <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> germ line mutations to these high rates, we conducted the first study of 176 Pakistani breast and ovarian cancer patients, selected on family history and on age of diagnosis. Comprehensive <jats:italic>BRCA<\/jats:italic> mutation screening was performed using a range of techniques, including denaturing high\u2010pressure liquid chromatography, single strand conformational polymorphism analysis and protein truncation test, followed by DNA sequencing. Thirty deleterious germ\u2010line mutations were identified in the 176 families (17.0%), including 23 in <jats:italic>BRCA1<\/jats:italic> and 7 in <jats:italic>BRCA2<\/jats:italic>. Four mutations, 185delAG, 185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all identified <jats:italic>BRCA1<\/jats:italic> mutations. Haplotype analyses suggested founder effects for 3 of these. The prevalence of <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> mutations was 42.8% for families with multiple cases of breast cancer, and was 50.0% for the breast\/ovarian cancer families. The prevalence of mutations was 11.9% for single cases of early\u2010onset breast cancer (\u226430 years) and was 9.0% for single cases of early\u2010onset ovarian cancer (\u226445 years). Our findings show that <jats:italic>BRCA<\/jats:italic> mutations account for a substantial proportion of hereditary breast\/ovarian cancer and early\u2010onset breast and ovarian cancer cases in Pakistan. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.22269","type":"journal-article","created":{"date-parts":[[2006,9,22]],"date-time":"2006-09-22T14:59:53Z","timestamp":1158937193000},"page":"2832-2839","source":"Crossref","is-referenced-by-count":99,"title":["Prevalence of <i>BRCA1<\/i> and <i>BRCA2<\/i> mutations in Pakistani breast and ovarian cancer patients"],"prefix":"10.1002","volume":"119","author":[{"given":"Muhammad U.","family":"Rashid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anbreen","family":"Zaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Sultan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Benner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Naqvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul R.","family":"Shakoori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Seidel\u2010Renkert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humirah","family":"Farooq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Narod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hamann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,26]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"77","article-title":"Karachi Cancer Registry data\u2013\u2013implications for the national cancer control program of Pakistan","volume":"5","author":"Bhurgri Y","year":"2004","journal-title":"Asian Pac J Cancer Prev"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000201)85:3<325::AID-IJC5>3.0.CO;2-J"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"e_1_2_6_5_2","series-title":"Cancer incidence in five continents","author":"Parkin DM","year":"1997"},{"key":"e_1_2_6_6_2","first-page":"251","article-title":"Breast carcinoma in Pakistani women","volume":"15","author":"Usmani K","year":"1996","journal-title":"J Environ Pathol Toxicol Oncol"},{"key":"e_1_2_6_7_2","first-page":"114","article-title":"Is carcinoma breast a different disease in Pakistani population?","volume":"47","author":"Ahmed R","year":"1997","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_6_8_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_9_2","first-page":"547","article-title":"Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2","volume":"59","author":"Rebbeck TR","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_10_2","first-page":"254","article-title":"An evaluation of genetic heterogeneity in 145 breast\u2010ovarian cancer families. 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