{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T02:47:21Z","timestamp":1789354041491,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"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":[[2015,12,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling\/testing are not well\u2010defined. In the current study, the authors sought to determine mutation prevalence and characteristics that are predictive of an inherited predisposition for PAC.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A total of 175 consecutive patients with PAC who underwent clinical genetics assessment at Memorial Sloan Kettering Cancer Center between 2011 and 2014 were identified. Clinical data, family history, and germline results were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Among 159 patients with PAC who pursued genetic testing, 24 pathogenic mutations were identified (15.1%; 95% confidence interval, 9.5%\u201020.7%), including <jats:italic>BRCA2<\/jats:italic> (13 mutations), <jats:italic>BRCA1<\/jats:italic> (4 mutations), <jats:italic>p16<\/jats:italic> (2 mutations), <jats:italic>PALB2<\/jats:italic> (1 mutation), and Lynch syndrome (4 mutations). <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> prevalence was 13.7% in Ashkenazi Jewish (AJ) patients (95 patients) and 7.1% in non\u2010AJ patients (56 patients). In AJ patients with a strong, weak, or absent family history of <jats:italic>BRCA<\/jats:italic>\u2010associated cancers, the mutation prevalence was 16.7%, 15.8%, and 7.4%, respectively. The mean age at the time of diagnosis in all mutation carriers was 58.5 years (range, 45\u201075 years) compared with 64 years (range, 27\u201087 years) in those not carrying a mutation (<jats:italic>P\u2009=\u2009<\/jats:italic>.02). Although <jats:italic>BRCA2<\/jats:italic> was the most common mutation identified, no patients with early\u2010onset PAC (diagnosed at age\u2009\u2264\u200950 years) harbored a <jats:italic>BRCA2<\/jats:italic> mutation and the mean age at diagnosis in <jats:italic>BRCA2<\/jats:italic> carriers was equivalent to that of individuals who were not mutation carriers (<jats:italic>P\u2009=\u2009<\/jats:italic>.34). Mutation prevalence in patients with early\u2010onset disease (21 patients) was 28.6%, including <jats:italic>BRCA1<\/jats:italic> (2 mutations), <jats:italic>p16<\/jats:italic> (2 mutations), <jats:italic>MSH2<\/jats:italic> (1 mutation), and <jats:italic>MLH1<\/jats:italic> (1 mutation).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Mutations in <jats:italic>BRCA2<\/jats:italic> account for\u2009&gt;\u200950% of patients with PAC with an identified susceptibility syndrome. AJ patients were found to have high <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> prevalence regardless of personal\/family history, suggesting that ancestry alone indicates a need for genetic evaluation. With the exception of <jats:italic>BRCA2<\/jats:italic>\u2010associated PAC, an inherited predisposition for PAC is associated with an earlier age at PAC diagnosis, suggesting that this subset of patients may also represent a population warranting further evaluation. <jats:bold><jats:italic>Cancer<\/jats:italic> 2015;121:4382\u20138.<\/jats:bold> \u00a9 <jats:italic>2015 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29664","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T10:09:00Z","timestamp":1444126140000},"page":"4382-4388","source":"Crossref","is-referenced-by-count":186,"title":["Identification of germline genetic mutations in patients with pancreatic cancer"],"prefix":"10.1002","volume":"121","author":[{"given":"Erin E.","family":"Salo\u2010Mullen","sequence":"first","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M.","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Kelsen","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad M.","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeve A.","family":"Lowery","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth H.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane L.","family":"Reidy","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lincoln","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amethyst","family":"Saldia","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohini","family":"Rau\u2010Murthy","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Saltz","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Offit","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Robson","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia K.","family":"Stadler","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(05)70249-2"},{"key":"e_1_2_7_3_1","article-title":"Frequency of a family history of pancreatic malignancy in patients with pancreatic malignancy","author":"Norton ID","year":"1998","journal-title":"Pancreas."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028829"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.18.1358"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.18.1365"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.15.1310"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.483"},{"key":"e_1_2_7_9_1","first-page":"3789","article-title":"Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%","volume":"62","author":"Murphy KM","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199510123331504"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65440-5"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1529"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70265-5"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-141"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e328349e2f8"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171202"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-010-9414-x"},{"key":"e_1_2_7_18_1","volume-title":"NCCN Clinical Practice Guidelines in Oncology","author":"National Comprehensive Cancer Network","year":"2015"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.5546"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26191"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900212"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.418"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2011-0185"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2728"},{"issue":"5","key":"e_1_2_7_25_1","article-title":"Phase IB trial of cisplatin (C), gemcitabine (G), and veliparib (V) in patients with known or potential BRCA or PALB2\u2010mutated pancreas adenocarcinoma (PC) [abstract]","volume":"32","author":"O'Reilly EM","year":"2014","journal-title":"J Clin Oncol."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.11.042"},{"key":"e_1_2_7_27_1","article-title":"Germline BRCA mutations in a large clinic\u2010based cohort of patients with pancreatic adenocarcinoma [published online ahead of print May 4, 2015]","author":"Holter S","journal-title":"J Clin Oncol."},{"key":"e_1_2_7_28_1","article-title":"Genome sequencing of multiple primary tumors reveals a novel PALB2 variant [published online ahead of print June 30, 2014]","author":"Schrader KA","journal-title":"J Clin Oncol."},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.29664","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.29664","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.29664","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T09:00:34Z","timestamp":1760259634000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.29664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,6]]},"references-count":28,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2015,12,15]]}},"alternative-id":["10.1002\/cncr.29664"],"URL":"https:\/\/doi.org\/10.1002\/cncr.29664","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,6]]}}}