{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:55:30Z","timestamp":1790808930909,"version":"4.1.0"},"reference-count":104,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer (PC) is one of the most devastating malignancies; it has a 5-year survival rate of only 9%, and novel treatment strategies are urgently needed. While most PC cases occur sporadically, PC associated with hereditary syndromes or familial PC (FPC; defined as an individual having two or more first-degree relatives diagnosed with PC) accounts for about 10% of cases. Hereditary cancer syndromes associated with increased risk for PC include Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma, familial adenomatous polyposis, Lynch syndrome and hereditary breast and ovarian cancer syndrome. Next-generation sequencing of FPC patients has uncovered new susceptibility genes such as PALB2 and ATM, which participate in homologous recombination repair, and further investigations are in progress. Previous studies have demonstrated that some sporadic cases that do not fulfil FPC criteria also harbor similar mutations, and so genomic testing based on family history might overlook some susceptibility gene carriers. There are no established screening procedures for high-risk unaffected cases, and it is not clear whether surveillance programs would have clinical benefits. In terms of treatment, poly (ADP-ribose) polymerase inhibitors for BRCA-mutated cases or immune checkpoint inhibitors for mismatch repair deficient cases are promising, and clinical trials of these agents are underway.<\/jats:p>","DOI":"10.3390\/ijms20030561","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T11:27:52Z","timestamp":1548761272000},"page":"561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Genomic Features and Clinical Management of Patients with Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3642-2032","authenticated-orcid":false,"given":"Akihiro","family":"Ohmoto","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Yachida","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan"},{"name":"Department of Cancer Genome Informatics, Graduate School of Medicine\/Faculty of Medicine, Osaka University, Osaka 5650871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chigusa","family":"Morizane","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 1040045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2018, September 28). Five-Year Survival Rate Comes from SEER-9 Data. Cancer Facts & Figures 2018. Available online: https:\/\/www.pancan.org\/facing-pancreatic-cancer\/about-pancreatic-cancer\/survival-rate\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/mc.20855","article-title":"Genetic susceptibility to pancreatic cancer","volume":"51","author":"Klein","year":"2012","journal-title":"Mol. Carcinog."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"761","DOI":"10.5009\/gnl16414","article-title":"Familial pancreatic cancer and the future of directed screening","volume":"11","author":"Welinsky","year":"2017","journal-title":"Gut Liver"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1097\/MPA.0b013e3181a86b2c","article-title":"Should patients with a strong family history of pancreatic cancer be screened on a periodic basis for cancer of the pancreas?","volume":"38","author":"Steinberg","year":"2009","journal-title":"Pancreas"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ajg.2014.435","article-title":"ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes","volume":"110","author":"Syngal","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"365","DOI":"10.5858\/133.3.365","article-title":"Familial pancreatic cancer","volume":"133","author":"Shi","year":"2009","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1097\/MPA.0000000000001136","article-title":"Germline variants and risk for pancreatic cancer: A systematic review and emerging concepts","volume":"47","author":"Zhan","year":"2018","journal-title":"Pancreas"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1053\/gast.2000.20228","article-title":"Very high risk of cancer in familial Peutz-Jeghers syndrome","volume":"119","author":"Giardiello","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1158\/1078-0432.CCR-06-0083","article-title":"Frequency and spectrum of cancers in the Peutz-Jeghers syndrome","volume":"12","author":"Hearle","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1053\/j.gastro.2004.03.014","article-title":"Relative frequency and morphology of cancers in STK11 mutation carriers","volume":"126","author":"Lim","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bpg.2009.02.001","article-title":"Hereditary pancreatic cancer: A clinical perspective","volume":"23","author":"Greer","year":"2009","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.228452.113","article-title":"Familial pancreatic cancer: Genetic advances","volume":"28","author":"Rustgi","year":"2014","journal-title":"Genes Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/jnci\/89.6.442","article-title":"Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary PancreatitisStudy Group","volume":"89","author":"Lowenfels","year":"1997","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1572-0241.2007.01597.x","article-title":"Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: A national exhaustive series","volume":"103","author":"Rebours","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/s41395-018-0194-5","article-title":"Hereditary pancreatitis in the United States: Survival and rates of pancreatic cancer","volume":"113","author":"Shelton","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.pan.2016.04.009","article-title":"The clinical course of hereditary pancreatitis in children\u2014A comprehensive analysis of 41 cases","volume":"16","author":"Oracz","year":"2016","journal-title":"Pancreatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/gut.2008.149179","article-title":"The natural history of hereditary pancreatitis: A national series","volume":"58","author":"Rebours","year":"2009","journal-title":"Gut"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s00535-017-1388-0","article-title":"Nationwide survey of hereditary pancreatitis in Japan","volume":"53","author":"Masamune","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.yasu.2010.05.011","article-title":"Update on familial pancreatic cancer","volume":"44","author":"Hruban","year":"2010","journal-title":"Adv. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/1097-0215(20000915)87:6<809::AID-IJC8>3.0.CO;2-U","article-title":"Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden)","volume":"87","author":"Vasen","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_22","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."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7151","DOI":"10.1158\/1078-0432.CCR-08-0403","article-title":"Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families","volume":"14","author":"Bishop","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s10689-016-9888-2","article-title":"Familial atypical multiple mole melanoma (FAMMM) syndrome: History, genetics, and heterogeneity","volume":"15","author":"Lynch","year":"2016","journal-title":"Fam. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1053\/j.gastro.2010.11.048","article-title":"Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a p16-Leiden mutation","volume":"140","author":"Vasen","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11182","DOI":"10.3748\/wjg.v20.i32.11182","article-title":"Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection","volume":"20","author":"Becker","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1136\/gut.34.10.1394","article-title":"Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis","volume":"34","author":"Giardiello","year":"1993","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/MPA.0000000000000295","article-title":"Familial adenomatous polyposis and pancreatic cancer","volume":"44","author":"Moussata","year":"2015","journal-title":"Pancreas"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/S0002-9440(10)63008-8","article-title":"Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas: Frequent alterations in the APC\/beta-catenin pathway and chromosome 11p","volume":"159","author":"Abraham","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/humu.21446","article-title":"Recurrence and variability of germline EPCAM deletions in Lynch syndrome","volume":"32","author":"Kuiper","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/jnci\/djh034","article-title":"Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability","volume":"96","author":"Umar","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_32","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"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1136\/gutjnl-2017-314057","article-title":"Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: A report from the Prospective Lynch Syndrome Database","volume":"67","author":"Bernstein","year":"2018","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00535-018-1466-y","article-title":"Germline variants in pancreatic cancer patients with a personal or family history of cancer fulfilling the revised Bethesda guidelines","volume":"53","author":"Ohmoto","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1158\/1078-0432.CCR-17-3099","article-title":"Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: Challenges and recommendations","volume":"24","author":"Hu","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1200\/EDBK_208341","article-title":"Recent advances in lynch syndrome: Diagnosis, treatment, and cancer prevention","volume":"38","author":"Yurgelun","year":"2018","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10147-017-1208-9","article-title":"Management of hereditary breast and ovarian cancer","volume":"23","author":"Yamauchi","year":"2018","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_38","unstructured":"Centers for Disease Control and Prevention (2018, December 25). HBOC Syndrome. Inside Knowledge about Gynecologic Cancer, Available online: https:\/\/www.cdc.gov\/cancer\/knowledge\/provider-education\/genetics\/hboc-syndrome.htm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.cancergencyto.2004.01.032","article-title":"BRCA1 and pancreatic cancer: Pedigree findings and their causal relationships","volume":"158","author":"Lynch","year":"2005","journal-title":"Cancer Genet Cytogenet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1038\/bjc.2012.483","article-title":"The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers","volume":"107","author":"Iqbal","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/cncr.29041","article-title":"Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian","volume":"121","author":"Mersch","year":"2015","journal-title":"Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.pan.2015.04.003","article-title":"A histomorphologic comparison of familial and sporadic pancreatic cancers","volume":"15","author":"Singhi","year":"2015","journal-title":"Pancreatology"},{"key":"ref_43","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":"ref_44","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":"Egan","year":"2009","journal-title":"Fam. Cancer"},{"key":"ref_45","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"},{"key":"ref_46","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","year":"2002","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/jnci\/95.3.214","article-title":"BRCA2 germline mutations in familial pancreatic carcinoma","volume":"95","author":"Hahn","year":"2003","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1056\/NEJM199705153362001","article-title":"The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews","volume":"336","author":"Struewing","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4161\/cbt.8.2.7136","article-title":"Absence of germline BRCA1 mutations in familial pancreatic cancer patients","volume":"8","author":"Axilbund","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_50","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"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/ng1959","article-title":"PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene","volume":"39","author":"Rahman","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1399-0004.2010.01425.x","article-title":"PALB2 mutations in European familial pancreatic cancer families","volume":"78","author":"Slater","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_53","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."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.2147\/OTT.S139336","article-title":"Current status of poly(ADP-ribose) polymerase inhibitors and future directions","volume":"10","author":"Ohmoto","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1136\/jmedgenet-2011-100281","article-title":"CDKN2A is the main susceptibility gene in Italian pancreatic cancer families","volume":"49","author":"Ghiorzo","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10689-006-7850-4","article-title":"Low frequency of CHEK2 mutations in familial pancreatic cancer","volume":"5","author":"Bartsch","year":"2006","journal-title":"Fam. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"430","DOI":"10.4143\/crt.2016.217","article-title":"The prevalence of founder mutations among individuals from families with familial pancreatic cancer syndrome","volume":"49","author":"Lener","year":"2017","journal-title":"Cancer Res. Treat."},{"key":"ref_58","first-page":"2585","article-title":"Fanconi anemia gene mutations in young-onset pancreatic cancer","volume":"63","author":"Yeo","year":"2003","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1158\/0008-5472.383.65.2","article-title":"Germ line Fanconi anemia complementation group C mutations and pancreatic cancer","volume":"65","author":"Couch","year":"2005","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pogue-Geile, K.L., Chen, R., Bronner, M.P., Crnogorac-Jurcevic, T., Moyes, K.W., Dowen, S., Otey, C.A., Crispin, D.A., George, R.D., and Whitcomb, D.C. (2006). Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030516"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Slater, E., Amrillaeva, V., Fendrich, V., Bartsch, D., Earl, J., Vitone, L.J., Neoptolemos, J.P., and Greenhalf, W. (2007). Palladin mutation causes familial pancreatic cancer: Absence in European families. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040164"},{"key":"ref_62","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."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/gim.2014.153","article-title":"BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: A PACGENE study","volume":"17","author":"Zhen","year":"2015","journal-title":"Genet. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1053\/j.gastro.2014.11.042","article-title":"Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer","volume":"148","author":"Grant","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Petersen, G.M., Chaffee, K.G., McWilliams, R.R., Majithia, N., Allen, B., Kidd, J., Singh, N., Hartman, A.R., and Oberg, A. (2016). Genetic heterogeneity and survival among pancreatic adenocarcinoma (PDAC) patients with positive family history. J. Clin. Oncol., 34.","DOI":"10.1200\/JCO.2016.34.15_suppl.4108"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"74227","DOI":"10.18632\/oncotarget.12490","article-title":"Germline mutations in Japanese familial pancreatic cancer patients","volume":"7","author":"Takai","year":"2016","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1158\/1055-9965.EPI-15-0455","article-title":"Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients","volume":"25","author":"Hu","year":"2016","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_68","unstructured":"Yurgelun, M.B., Chittenden, A.B., Morales-Oyarvide, V., Rubinson, D.A., Dunne, R.F., Kozak, M.M., Qian, Z.R., Welch, M.W., Brais, L.K., and Da Silva, A. (2018). Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes inpatients with resected pancreatic cancer. Genet. Med."},{"key":"ref_69","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."},{"key":"ref_70","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"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1002\/cncr.31628","article-title":"Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma","volume":"124","author":"Brand","year":"2018","journal-title":"Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1200\/JCO.2006.09.2452","article-title":"PancPRO: Risk assessment for individuals with a family history of pancreatic cancer","volume":"25","author":"Wang","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1136\/gut.2006.108456","article-title":"Advances in counselling and surveillance of patients at risk for pancreatic cancer","volume":"56","author":"Brand","year":"2007","journal-title":"Gut"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1136\/gutjnl-2012-303108","article-title":"International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer","volume":"62","author":"Canto","year":"2013","journal-title":"Gut"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1053\/j.seminoncol.2007.05.008","article-title":"Strategies for screening for pancreatic adenocarcinoma in high-risk patients","volume":"34","author":"Canto","year":"2007","journal-title":"Semin. Oncol."},{"key":"ref_76","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."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1053\/j.gastro.2018.05.035","article-title":"Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance","volume":"155","author":"Canto","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8678","DOI":"10.3748\/wjg.v21.i28.8678","article-title":"Screening for pancreatic cancer in familial high-risk individuals: A systematic review","volume":"21","author":"Lu","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/bjc.2014.418","article-title":"Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers","volume":"111","author":"Golan","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1158\/1078-0432.CCR-18-1472","article-title":"Germline and somatic DNA damage repair gene mutations and overall survival in metastatic pancreatic adenocarcinoma patients treated with FOLFIRINOX","volume":"24","author":"Sehdev","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_81","unstructured":"(2018, December 25). NCCN Guidelines Version 2.2018 Pancreatic Adenocarcinoma. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/default.aspx."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"viii205","DOI":"10.1093\/annonc\/mdy282.114","article-title":"Phase II clinical trial of gemcitabine plus oxaliplatin combination therapy (GEMOX) in patients with advanced pancreatic adenocarcinoma with a family history of pancreatic breast ovarian prostate cancer or personal history of breast ovarian prostate cancer","volume":"29","author":"Takahashi","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1002\/cncr.31307","article-title":"PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside","volume":"124","author":"Turk","year":"2018","journal-title":"Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nature03445","article-title":"Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy","volume":"434","author":"Farmer","year":"2005","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nature03443","article-title":"Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase","volume":"434","author":"Bryant","year":"2005","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1200\/JCO.2014.56.2728","article-title":"Olaparib monotherapy in patients with advanced cancer and a germline BRCA1\/2 mutation","volume":"33","author":"Kaufman","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Shroff, R.T., Hendifar, A., McWilliams, R.R., Geva, R., Epelbaum, R., Rolfe, L., Goble, S., Lin, K.K., Biankin, A.V., and Giordano, H. (2018). Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO Precis. Oncol.","DOI":"10.1200\/PO.17.00316"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejca.2017.11.004","article-title":"Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma","volume":"89","author":"Lowery","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1158\/2159-8290.CD-16-1250","article-title":"Phase I, dose-escalation, two-parttrial of the PARP inhibitor talazoparib in patients with advanced germline BRCA1\/2 mutations and selected sporadic cancers","volume":"7","author":"Ramanathan","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1002\/cncr.31218","article-title":"Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma","volume":"124","author":"Lee","year":"2018","journal-title":"Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s00432-018-2666-9","article-title":"Emerging strategies in BRCA-positive pancreatic cancer","volume":"144","author":"Kowalewski","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"8109","DOI":"10.1158\/0008-5472.CAN-06-0140","article-title":"Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly (ADP-ribose) polymerase inhibition","volume":"66","author":"McCabe","year":"2006","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrc.2015.21","article-title":"BRCAness revisited","volume":"16","author":"Lord","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ags3.12176","article-title":"Immunotherapy for pancreatic cancer: Barriers and breakthroughs","volume":"2","author":"Torphy","year":"2018","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40425-016-0119-z","article-title":"From bench to bedside a comprehensive review of pancreatic cancer immunotherapy","volume":"4","author":"Kunk","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","volume":"366","author":"Brahmer","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/S1470-2045(17)30422-9","article-title":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study","volume":"18","author":"Overman","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"ref_100","unstructured":"(2018, December 25). Prescribing Information of KEYTRUDA, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/125514s014lbl.pdf."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1053\/j.gastro.2016.09.060","article-title":"Hypermutation in pancreatic cancer","volume":"152","author":"Humphris","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13073-016-0364-2","article-title":"Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: The Princess Margaret IMPACT\/COMPACT trial","volume":"8","author":"Stockley","year":"2016","journal-title":"Genome Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12943-016-0553-z","article-title":"Comprehensive screening of target molecules by next-generation sequencing in patients with malignant solid tumors: Guiding entry into phase I clinical trials","volume":"15","author":"Tanabe","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3748\/wjg.v23.i6.935","article-title":"Familial pancreatic cancer: Concept, management and issues","volume":"23","author":"Matsubayashi","year":"2017","journal-title":"World J. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/561\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:29:17Z","timestamp":1760185757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,29]]},"references-count":104,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijms20030561"],"URL":"https:\/\/doi.org\/10.3390\/ijms20030561","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,29]]}}}