{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:34:22Z","timestamp":1793648062447,"version":"4.5.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,8,27]],"date-time":"2022-08-27T00:00:00Z","timestamp":1661558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50 CA62924"],"award-info":[{"award-number":["P50 CA62924"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lustgarten Foundation, Rolfe Pancreatic Cancer Foundation, Dennis Troper and Susan Wojcicki","id":[{"id":"https:\/\/ror.org\/02p524v68","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Sol Goldman Pancreatic Cancer Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (&amp;gt;1 relative) are imprecise because of small samples sizes or potentially impacted by biases inherent in retrospective data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study is to determine the age-specific pancreatic cancer risk as a function of family history using prospective data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared pancreatic cancer incidence (n\u2009=\u2009167) in 21\u200a141 individuals from 4433 families enrolled in the National Familial Pancreatic Cancer Registry with that expected based on Surveillance Epidemiology and End Results data and estimated the cumulative probability of pancreatic cancer using competing risk regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Familial pancreatic kindred members (kindreds with pancreatic cancer in 2 first-degree relatives [FDRs] or a pathogenic variant) had a standardized incidence ratio of 4.86 (95% confidence interval [CI] = 4.01 to 5.90), and sporadic kindred members (kindreds not meeting familial criteria) had a standardized incidence ratio of 2.55 (95% CI = 1.95 to 3.34). Risk in familial pancreatic cancer kindreds increased with an increasing number of FDRs with pancreatic cancer, with a standardized incidence ratio of 3.46 (95% CI = 2.52 to 4.76), 5.44 (95% CI = 4.07 to 7.26), and 10.78 (95% CI = 6.87 to 16.89) for 1, 2, and 3 or more FDRs with pancreatic cancer, respectively. Risk was also higher among individuals with a family history of young-onset (aged younger than 50 years) pancreatic cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pancreatic cancer risk is strongly dependent on family history, including both the degree of relationship(s) and age of onset of pancreatic cancer in relatives. These risk estimates will help inform the design of early detection studies and the risk and benefit analysis of screening trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djac167","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T16:51:53Z","timestamp":1661532713000},"page":"1681-1688","source":"Crossref","is-referenced-by-count":43,"title":["Risk of Pancreatic Cancer in the Long-Term Prospective Follow-Up of Familial Pancreatic Cancer Kindreds"],"prefix":"10.1093","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3548-2460","authenticated-orcid":false,"given":"Nancy","family":"Porter","sequence":"first","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-0200","authenticated-orcid":false,"given":"Daniel","family":"Laheru","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-612X","authenticated-orcid":false,"given":"Bryan","family":"Lau","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9149-2247","authenticated-orcid":false,"given":"Jin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Narang","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"Roberts","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-3032","authenticated-orcid":false,"given":"Marcia I","family":"Canto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8957-3945","authenticated-orcid":false,"given":"Anne Marie","family":"Lennon","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"Department of Surgery, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"Division of Radiation Oncology, Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4286-2296","authenticated-orcid":false,"given":"Michael G","family":"Goggins","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University , Baltimore, MD, USA"},{"name":"Division of Gastroenterology, Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-5672","authenticated-orcid":false,"given":"Ralph H","family":"Hruban","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2737-8399","authenticated-orcid":false,"given":"Alison P","family":"Klein","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins School of Medicine , Baltimore, MD, USA"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA"},{"name":"The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University , Baltimore, MD, USA"},{"name":"Division of Gastroenterology, Department of Medicine, Johns Hopkins School of Medicine , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,27]]},"reference":[{"issue":"1","key":"2022121307565289200_djac167-B1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"issue":"7","key":"2022121307565289200_djac167-B2","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1158\/1055-9965.EPI-18-1235","article-title":"Analysis of heritability and genetic architecture of pancreatic cancer: a PanC4 study","volume":"28","author":"Chen","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"2","key":"2022121307565289200_djac167-B3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1056\/NEJM200007133430201","article-title":"Environmental and heritable factors in the causation of cancer\u2013analyses of cohorts of twins from Sweden, Denmark, and Finland","volume":"343","author":"Lichtenstein","year":"2000","journal-title":"N Engl J Med"},{"issue":"2","key":"2022121307565289200_djac167-B4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1158\/2159-8290.CD-15-0402","article-title":"Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer","volume":"6","author":"Roberts","year":"2016","journal-title":"Cancer Discov"},{"issue":"1","key":"2022121307565289200_djac167-B5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1158\/2159-8290.CD-11-0194","article-title":"ATM mutations in patients with hereditary pancreatic cancer","volume":"2","author":"Roberts","year":"2012","journal-title":"Cancer Discov"},{"issue":"23","key":"2022121307565289200_djac167-B6","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"},{"issue":"18","key":"2022121307565289200_djac167-B7","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1093\/jnci\/94.18.1358","article-title":"Cancer Incidence in BRCA1 mutation carriers","volume":"94","author":"Thompson","year":"2002","journal-title":"J Natl Cancer Inst"},{"issue":"5924","key":"2022121307565289200_djac167-B8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1126\/science.1171202","article-title":"Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene","volume":"324","author":"Jones","year":"2009","journal-title":"Science"},{"issue":"16","key":"2022121307565289200_djac167-B9","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1001\/jama.2009.1529","article-title":"Risk of pancreatic cancer in families with Lynch syndrome","volume":"302","author":"Kastrinos","year":"2009","journal-title":"JAMA"},{"issue":"15","key":"2022121307565289200_djac167-B10","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1056\/NEJM199510123331504","article-title":"Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations","volume":"333","author":"Goldstein","year":"1995","journal-title":"N Engl J Med"},{"issue":"1","key":"2022121307565289200_djac167-B11","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41467-018-02942-5","article-title":"Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer","volume":"9","author":"Klein","year":"2018","journal-title":"Nat Commun"},{"issue":"7","key":"2022121307565289200_djac167-B12","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41575-021-00457-x","article-title":"Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors","volume":"18","author":"Klein","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"7","key":"2022121307565289200_djac167-B13","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1093\/annonc\/mdr541","article-title":"Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)","volume":"23","author":"Bosetti","year":"2012","journal-title":"Ann Oncol"},{"issue":"4","key":"2022121307565289200_djac167-B14","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/aje\/kwp134","article-title":"Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium","volume":"170","author":"Lynch","year":"2009","journal-title":"Am J Epidemiol"},{"issue":"23","key":"2022121307565289200_djac167-B15","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1001\/jama.2018.6228","article-title":"Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer","volume":"319","author":"Hu","year":"2018","journal-title":"JAMA"},{"issue":"30","key":"2022121307565289200_djac167-B16","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1200\/JCO.2017.72.3502","article-title":"Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma","volume":"35","author":"Shindo","year":"2017","journal-title":"J Clin Oncol"},{"issue":"1","key":"2022121307565289200_djac167-B17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41436-018-0009-5","article-title":"Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer","volume":"21","author":"Yurgelun","year":"2019","journal-title":"Genet Med"},{"issue":"3-4","key":"2022121307565289200_djac167-B18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF02924156","article-title":"Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada","volume":"10","author":"Ghadirian","year":"1991","journal-title":"Int J Pancreatol"},{"issue":"1","key":"2022121307565289200_djac167-B19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/1520-6866(2001)21:1<7::AID-TCM3>3.0.CO;2-A","article-title":"Risk factors for pancreatic cancer: a case-control study based on direct interviews","volume":"21","author":"Silverman","year":"2001","journal-title":"Teratog Carcinog Mutagen"},{"issue":"6","key":"2022121307565289200_djac167-B20","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/ijc.25148","article-title":"Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)","volume":"127","author":"Jacobs","year":"2010","journal-title":"Int J Cancer"},{"issue":"2","key":"2022121307565289200_djac167-B21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/jnci\/djp466","article-title":"Importance of age of onset in pancreatic cancer kindreds","volume":"102","author":"Brune","year":"2010","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"2022121307565289200_djac167-B22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10689-008-9214-8","article-title":"Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis","volume":"8","author":"Permuth-Wey","year":"2009","journal-title":"Fam Cancer"},{"issue":"3","key":"2022121307565289200_djac167-B23","doi-asserted-by":"crossref","first-page":"e65","DOI":"10.1371\/journal.pmed.0010065","article-title":"Cancer as a complex phenotype: pattern of cancer distribution within and beyond the nuclear family","volume":"1","author":"Amundadottir","year":"2004","journal-title":"PLoS Med"},{"issue":"4","key":"2022121307565289200_djac167-B24","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1158\/1055-9965.EPI-05-0734","article-title":"Pancreatic cancer genetic epidemiology consortium","volume":"15","author":"Petersen","year":"2006","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"1","key":"2022121307565289200_djac167-B25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1136\/gutjnl-2019-319352","article-title":"Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","volume":"69","author":"Goggins","year":"2020","journal-title":"Gut"},{"issue":"5","key":"2022121307565289200_djac167-B26","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s11605-019-04230-z","article-title":"Surgical outcomes after pancreatic resection of screening-detected lesions in individuals at high risk for developing pancreatic cancer","volume":"24","author":"Canto","year":"2020","journal-title":"J Gastrointest Surg"},{"issue":"7","key":"2022121307565289200_djac167-B27","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1158\/0008-5472.CAN-03-3823","article-title":"Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds","volume":"64","author":"Klein","year":"2004","journal-title":"Cancer Res"},{"key":"2022121307565289200_djac167-B28","author":"National Cancer Institute. Surveillance Research Program"},{"issue":"446","key":"2022121307565289200_djac167-B29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","article-title":"A proportional hazards model for the subdistribution of a competing risk","volume":"94","author":"Fine","year":"1999","journal-title":"J Am Stat Assoc"},{"key":"2022121307565289200_djac167-B30","author":"SAS Institute Inc"},{"key":"2022121307565289200_djac167-B31","author":"R Core Team","year":"2020"},{"key":"2022121307565289200_djac167-B32","author":"StataCorp","year":"2019"},{"issue":"5","key":"2022121307565289200_djac167-B33","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1001\/jama.2019.10232","article-title":"Screening for pancreatic cancer: US Preventive Services Task Force reaffirmation recommendation statement","volume":"322","author":"Owens","year":"2019","journal-title":"JAMA"},{"issue":"17","key":"2022121307565289200_djac167-B34","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1200\/JCO.2015.64.0730","article-title":"Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers","volume":"34","author":"Vasen","year":"2016","journal-title":"J Clin Oncol"},{"issue":"38","key":"2022121307565289200_djac167-B35","doi-asserted-by":"crossref","first-page":"10202","DOI":"10.1073\/pnas.1704961114","article-title":"Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers","volume":"114","author":"Cohen","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022121307565289200_djac167-B36","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.gim.2022.01.016","article-title":"Pancreatic cancer risk to siblings of probands in bilineal cancer settings","author":"Rabe","year":"2022","journal-title":"Genet Med"},{"issue":"7","key":"2022121307565289200_djac167-B37","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/ijc.30203","article-title":"Validity of self-reported family history of cancer: a systematic literature review on selected cancers","volume":"139","author":"Fiederling","year":"2016","journal-title":"Int J Cancer"},{"issue":"2","key":"2022121307565289200_djac167-B38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/ajmg.10110","article-title":"All in the family: evaluation of the process and content of sisters\u2019 communication about BRCA1 and BRCA2 genetic test results","volume":"107","author":"Hughes","year":"2002","journal-title":"Am J Med Genet"}],"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djac167\/46127422\/djac167.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/114\/12\/1681\/47761983\/djac167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/114\/12\/1681\/47761983\/djac167.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T03:36:47Z","timestamp":1670902607000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/article\/114\/12\/1681\/6677786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,27]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,8,27]]},"published-print":{"date-parts":[[2022,12,8]]}},"URL":"https:\/\/doi.org\/10.1093\/jnci\/djac167","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,12,1]]},"published":{"date-parts":[[2022,8,27]]}}}