{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:37:52Z","timestamp":1760729872398},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,7,5]],"date-time":"2007-07-05T00:00:00Z","timestamp":1183593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:p><jats:sc>lambda<\/jats:sc> is a model that estimates the probability an Ashkenazi Jewish (AJ) woman carries an ancestral <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> mutation from her personal and family cancer history. <jats:sc>lambda<\/jats:sc> is relevant to clinical practice, and its implementation does not require a computer. It was developed principally from Australian and UK data. We conducted a validation study using 1286 North American AJ women tested for the mutations 185delAG and 5382insC in <jats:italic>BRCA1<\/jats:italic> and 6174delT in <jats:italic>BRCA2<\/jats:italic>. Most had a personal or family history of breast cancer. We observed 197 carriers. The area under the receiver operator characteristic (ROC) curve (a measure of ranking) was 0.79 [95% confidence interval (CI) = 0.77\u20130.81], similar to that for the model\u2010generating data (0.78; 95% CI = 0.75\u20130.82). <jats:sc>lambda<\/jats:sc> predicted 232 carriers (18% more than observed; p = 0.002) and was overdispersed (p = 0.009). The Bayesian computer program <jats:sc>brcapro<\/jats:sc> gave a similar area under the ROC curve (0.78; 95% CI = 0.76\u20130.80), but predicted 367 carriers (86% more than observed; p &lt; 0.0001), and was substantially overdispersed (p &lt; 0.0001). Therefore, <jats:sc>lambda<\/jats:sc> is comparable to <jats:sc>brcapro<\/jats:sc> for ranking AJ women according to their probability of being a <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> mutation carrier and is more accurate than <jats:sc>brcapro<\/jats:sc> which substantially overpredicts carriers in this population.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2007.00841.x","type":"journal-article","created":{"date-parts":[[2007,7,6]],"date-time":"2007-07-06T08:01:52Z","timestamp":1183708912000},"page":"87-97","source":"Crossref","is-referenced-by-count":11,"title":["Validation study of the <scp>lambda<\/scp> model for predicting the <i>BRCA1<\/i> or <i>BRCA2<\/i> mutation carrier status of North American Ashkenazi Jewish women"],"prefix":"10.1111","volume":"72","author":[{"given":"C","family":"Apicella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JG","family":"Dowty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GS","family":"Dite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MA","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RT","family":"Senie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MB","family":"Daly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"IL","family":"Andrulis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EM","family":"John","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SS","family":"Buys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FP","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Glendon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ozcelik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Miron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Kotar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MC","family":"Southey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WD","family":"Foulkes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JL","family":"Hopper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,7,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/302320"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/gte.1997.1.47"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/301903"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199601183340302"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/302853"},{"key":"e_1_2_6_7_2","first-page":"1059","article-title":"Founder 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