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dc.contributor.authorEarl, Julie
dc.contributor.authorGalindo-Pumariño, Cristina
dc.contributor.authorEncinas, Jessica
dc.contributor.authorBarreto, Emma
dc.contributor.authorCastillo, Maria E
dc.contributor.authorPachón, Vanessa
dc.contributor.authorFerreiro, Reyes
dc.contributor.authorRodríguez-Garrote, Mercedes
dc.contributor.authorGonzález-Martínez, Silvia
dc.contributor.authorRamon Y Cajal, Teresa
dc.contributor.authorDiaz, Luis Robles
dc.contributor.authorChirivella-Gonzalez, Isabel
dc.contributor.authorRodriguez, Montse
dc.contributor.authorde Castro, Eva Martínez
dc.contributor.authorGarcía-Seisdedos, David
dc.contributor.authorMuñoz, Gloria
dc.contributor.authorRosa, Juan Manuel Rosa
dc.contributor.authorMarquez, Mirari
dc.contributor.authorCarrato, Alfredo
dc.contributor.authorMalats, Nuria
dc.description.abstractThe 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%-10%. The genetic basis is unknown in the majority of families although around 10%-13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes. Panel sequencing was performed of 35 genes associated with hereditary cancer in 43 PDAC cases from families with an apparent hereditary pancreatic cancer syndrome. Pathogenic variants were identified in 19% (5/26) of PDAC cases from pure FPC families in the genes MLH1, CDKN2A, POLQ and FANCM. Low frequency potentially pathogenic VUS were also identified in 35% (9/26) of PDAC cases from FPC families in the genes FANCC, MLH1, PMS2, CFTR, APC and MUTYH. Furthermore, an important proportion of PDAC cases harboured more than one pathogenic, likely pathogenic or potentially pathogenic VUS, highlighting the multigene phenotype of FPC. The genetic basis of familial or hereditary pancreatic cancer can be explained in 21% of families by previously described hereditary cancer genes. Low frequency variants in other DNA repair genes are also present in 35% of families which may contribute to the risk of pancreatic cancer development. This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund ''A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer: RTICC (RD12/0036/0073) and La Asociación Española contra el Cáncer: AECC (Grupos Coordinados Estables 2016).es_ES
dc.description.sponsorshipThis study was funded by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund "A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Tematica de investigacion cooperativa en cancer: RTICC (RD12/0036/0073) and La Asociacion Espanola contra el Cancer: AECC (Grupos Coordinados Estables 2016).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshGerm-Line Mutation es_ES
dc.subject.meshAdenocarcinoma es_ES
dc.subject.meshAdult es_ES
dc.subject.meshAged es_ES
dc.subject.meshAged, 80 and over es_ES
dc.subject.meshCyclin-Dependent Kinase Inhibitor p16 es_ES
dc.subject.meshDNA Helicases es_ES
dc.subject.meshDNA-Directed DNA Polymerase es_ES
dc.subject.meshFemale es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshMutL Protein Homolog 1 es_ES
dc.subject.meshMutation Rate es_ES
dc.subject.meshPancreatic Neoplasms es_ES
dc.subject.meshPedigree es_ES
dc.titleA comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants.es_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderBiomedical Research Network in Cancer: CIBERONC
dc.contributor.funderRed Tematica de investigacion cooperativa en cancer: RTICC
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Epidemiología Genética y Moleculares_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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