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9 r9 0 9 6 ? . ? 6 ? 6 G9 G9 9 ? : Date: _March 1st, 2014_________________
Principal Investigator: __Marcia Irene Canto_______________
Application Number: __IRB00027287_________
JHM IRB - eForm A Protocol
Use the section headings to write the JHM IRB eForm A, inserting the appropriate material in each. If a section is not applicable, leave heading in and insert N/A.
When submitting JHM IRB eForm A (new or revised), enter the date submitted to the field at the top of JHM IRB eForm A.
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Abstract
Provide no more than a one page research abstract briefly stating the problem, the research hypothesis, and the importance of the research.
Various centers around the world are currently investigating the feasibility and yield of surveillance for pancreatic cancer in high-risk individuals. Evidence is beginning to accumulate that surveillance may lead to the early detection of non-invasive precursor lesions and asymptomatic early stage cancer. Ultimately, the goal of surveillance is to reduce mortality in these high risk individuals, but before this can be confirmed many research questions need to be answered. While the numbers of high-risk individuals screened in each separate screening facility are likely too small to properly address many of these questions, pooling data comprises a sizable sample size providing unique research opportunities. The objective of this study is retrospectively review all cases of high-risk individuals participating in our pancreatic surveillance program in whom 1) a suspicious precursor lesions was detected for which a pancreatic resection was performed and 2) in whom an advanced malignant disease was diagnosed. The de-identified information will be entered into an international multicenter database registry.
Objectives (include all primary and secondary objectives)
Primary aim of the registry is to determine the patient, lesion and surveillance factors associated with the development of pancreatic cancer in situ or invasive malignancy
Secondary aims of the registry are to:
Assess the indications for and type of pancreatic resections
Assess the specific types of pancreatic lesions
Assess the correlation between imaging and pathology
Assess all-cause and disease specific mortality
To determine survival time from point of diagnosis
Background (briefly describe pre-clinical and clinical data, current experience with procedures, drug or device, and any other relevant information to justify the research)
Pancreatic cancer is a deadly disease and the only hope for improvement of survival is early detection. Certain genetic syndromes are associated with a high risk of pancreatic cancer and screening for pancreatic cancer has become a relatively new strategy for familial pancreatic cancer. Our pancreatic cancer research group at Johns Hopkins and others have shown that screening with EUS and/or abdominal imaging tests such as CT/MRI can detect a relatively high number of significant pancreatic neoplasms (7-18%) in asymptomatic high risk individuals with an inherited predisposition for pancreatic ductal adenocarcinoma. Although most PC cases are thought to be sporadic, it is estimated that 5-15% of PC cases is caused by inherited genetic and/or familial factors ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_16" \o "Lynch, 1996 #129" 16, HYPERLINK \l "_ENREF_17" \o "Schneider, 2011 #1212" 17). Two distinct high-risk groups were previously identified. The first group of high-risk individuals consists of individuals in whom PC develops within the setting of a well-defined cancer susceptibility syndrome or inherited disease. Numerous germline mutations, leading to an increased risk for developing PC, have been discovered ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_18" \o "Kluijt, 2009 #1198" 18-27). They are listed in Table 1.
Table 1. Cancer susceptibility syndromes or inherited disease with a known elevated risk of developing pancreatic cancer
SyndromeGene(s)Risk of pancreatic cancerHereditary breast and ovarian cancer (HBOC)BRCA 1
BRCA 2RR 2-3
RR 3-10Familial cutaneous malignant melanoma (familial CMM) CDKN2A (p16)RR 8-45Hereditary pancreatitisPRSS1SIR 60-90Hereditary nonpolyposis colorectal cancer (Lynch syndrome)MLH1 / MSH2 / MSH6RR 9Peutz-Jeghers syndromeSTK11 / LKB1RR 75-135Familial adenomatous polyposis (FAP)APCRR 4.5Li-Fraumeni syndromep53RR 7.5RR, relative risk; SIR, standardized incidence ratio
The second and largest group consists of families with a strong family history of PC, but without a known cancer susceptibility syndrome or inherited disease. This condition is referred to as familial pancreatic cancer (FPC). Members of FPC kindred have an increased risk of PC. FPC kindred members with one first-degree relative (FDR) with PC have a 4.6-fold increased risk. This risk increases further as the number of FDRs with pancreatic cancer increases. FPC kindred members with two FDRs with PC have a 6.4-fold increased risk and those with three affected FDRs have a 32.0-fold increased risk of developing PC ADDIN EN.CITE Klein20041063(28)106310632817Klein, A. P.Brune, K. A.Petersen, G. M.Goggins, M.Tersmette, A. C.Offerhaus, G. J.Griffin, C.Cameron, J. L.Yeo, C. J.Kern, S.Hruban, R. H.Statistical Genetics Section, Inherited Disease Research Branch, National Human Genome Research Institute, NIH, Baltimore, Maryland, USA.Prospective risk of pancreatic cancer in familial pancreatic cancer kindredsCancer ResCancer Res2634-86472004/04/03AdultAgedFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleMiddle AgedPancreatic Neoplasms/epidemiology/*geneticsProspective StudiesRisk FactorsSEER Program2004Apr 10008-5472 (Print)
0008-5472 (Linking)15059921http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15059921http://cancerres.aacrjournals.org/content/64/7/2634.full.pdfeng( HYPERLINK \l "_ENREF_28" \o "Klein, 2004 #1063" 28). Individuals from FPC kindreds with at least one family member diagnosed with PC before the age of 50, are at an even greater risk of developing pancreatic cancer ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_29" \o "Brune, 2010 #1066" 29).
Surveillance of asymptomatic individuals is aimed to detect an early stage of non-symptomatic PC or, even more preferable, an advanced precursor lesion. Similar to the adenoma-carcinoma sequence in CRC, pancreatic cancer evolves through non-invasive precursor lesions. Known precursor lesions for PC are pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) ADDIN EN.CITE Maitra2005109(31)109109517Maitra, A.Fukushima, N.Takaori, K.Hruban, R. H.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231-2410, USA.Precursors to invasive pancreatic cancerAdv Anat PatholAdv Anat Pathol81-911222005/02/26Adenocarcinoma, Mucinous/genetics/*pathologyAdenocarcinoma, Papillary/genetics/*pathologyAnimalsCarcinoma in Situ/genetics/*pathologyCarcinoma, Pancreatic Ductal/genetics/*pathologyDisease Models, AnimalHumansMolecular BiologyPancreatic Neoplasms/genetics/*pathology2005Mar1072-4109 (Print)
1072-4109 (Linking)15731576http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15731576http://graphics.tx.ovid.com/ovftpdfs/FPDDNCGCBAGCNJ00/fs047/ovft/live/gv024/00125480/00125480-200503000-00006.pdf00125480-200503000-00006 [pii]eng( HYPERLINK \l "_ENREF_31" \o "Maitra, 2005 #109" 31). These precursor lesions are more common and of a higher grade in patients with a strong family history of pancreatic cancer than in patients with sporadic disease ADDIN EN.CITE Shi20091060(32)106010602617Shi, C.Klein, A. P.Goggins, M.Maitra, A.Canto, M.Ali, S.Schulick, R.Palmisano, E.Hruban, R. H.Authors' Affiliations: The Sol Goldman Pancreatic Cancer Research Center and Departments of Pathology, Oncology, Medicine, and Surgery, The Johns Hopkins Medical Institutions; and Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.Increased Prevalence of Precursor Lesions in Familial Pancreatic Cancer PatientsClin Cancer ResClin Cancer Res7737-774315242009/12/102009Dec 151078-0432 (Electronic)
1078-0432 (Linking)19996207http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19996207http://clincancerres.aacrjournals.org/content/15/24/7737.full.pdf27950801078-0432.CCR-09-0004 [pii]
10.1158/1078-0432.CCR-09-0004Eng( HYPERLINK \l "_ENREF_32" \o "Shi, 2009 #1060" 32). In sporadic cases, it is estimated that a precursor neoplastic clone will take approximately 11 to 12 years to evolve into a malignant clone and an additional 7 years to develop metastatic subclones ADDIN EN.CITE Yachida20131114(33)111411144917Yachida, S.Iacobuzio-Donahue, C. A.1] Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Division of Refractory Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.Evolution and dynamics of pancreatic cancer progressionOncogeneOncogene2013/02/192013Feb 181476-5594 (Electronic)
0950-9232 (Linking)23416985http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23416985http://www.nature.com/onc/journal/vaop/ncurrent/pdf/onc201329a.pdfonc201329 [pii]
10.1038/onc.2013.29Eng( HYPERLINK \l "_ENREF_33" \o "Yachida, 2013 #1114" 33). Although it is unknown whether the progression of PC in hereditary cases follows the same pace compared to sporadic cases, these findings do seem to provide a window of opportunity to perform a timely intervention before an advanced precursor lesion has evolved into cancer. Importantly, the premise of this strategy is that these precursor lesions can reliably be identified and stratified according to their risk of malignant transformation (i.e. degree of dysplasia) by a suitable surveillance technique.
The International Cancer of the Pancreas Screening (CAPS) Consortium was formed in 2010 to help organize global pancreatic screening and stimulate research to promote the development of evidence based surveillance protocols. Multiple hospitals from over the world are linked to the CAPS Consortium.
Taken together, these centers are screening a sizeable number of high-risk individuals. Individual sample sizes however, are too small to study whether surveillance of the pancreas leads to a reduction in mortality while outweighing costs and side effects of surveillance. When data from all centers arepooled into one worldwide registry, important research questions pertaining risk for development of pancreatic cancer, imaging and pathology of familial pancreatic neoplasia, and recommendations for pancreatic surveillance can be assessed much more readily and reliably. During the CAPS summit meeting in Baltimore, USA, in February 2011, it was therefore concluded that such an international registry should be developed (see attached publication). Using a step-by-step approach, it was decided to start by collecting data of individuals for whom pancreatic cancer surveillance led to the detection of advanced disease or the detection of a suspicious lesion for which pancreatic surgery was performed.
Study Procedures
Study design, including the sequence and timing of study procedures
(distinguish research procedures from those that are part of routine care).
All procedures have already been completes as part of the IRB approved CAPS 1, 2, 3, and 4 studies
Study duration and number of study visits required of research participants.
N/A this is a retrospective study
Blinding, including justification for blinding or not blinding the trial, if applicable.
N/A
Justification of why participants will not receive routine care or will have current therapy stopped.
Patients will all receive routine care
Justification for inclusion of a placebo or non-treatment group.
N/A
Definition of treatment failure or participant removal criteria.
N/A
Description of what happens to participants receiving therapy when study ends or if a participants participation in the study ends prematurely.
N/A
Inclusion/Exclusion Criteria
Inclusion criteria:
High risk individuals enrolled in the CAPS 1,2,3, and 4 studies
Who underwent surgical resection of a pancreatic lesion and/or
Diagnosed with a malignant lesion on EUS-FNA or percutaneous FNA
Drugs/ Substances/ Devices
The rationale for choosing the drug and dose or for choosing the device to be used.
N/A
Justification and safety information if FDA approved drugs will be administered for non-FDA approved indications or if doses or routes of administration or participant populations are changed.
N/A
Justification and safety information if non-FDA approved drugs without an IND will be administered.
N/A
Date: ____________________
Principal Investigator: _________________
Application Number: ___________
Study Statistics
Primary outcome variable.
Primary aim is to determine the patient, lesion and surveillance factors associated with the development of pancreatic cancer in situ or invasive malignancy
Secondary outcome variables.
Assess the indications for and type of pancreatic resections
Assess the specific types of pancreatic lesions
Assess the correlation between imaging and pathology
Assess all-cause and disease specific mortality
To determine survival time from point of diagnosis
Statistical plan including sample size justification and interim data analysis.
N/A
Early stopping rules.
N/A
Risks
Medical risks, listing all procedures, their major and minor risks and expected frequency.
All endoscopic procedures and surgical resections have already been performed as part of the CAPS 4 protocol and clinical care
Steps taken to minimize the risks.
All procedures are performed by expert endoscopists and pancreatic surgeons at Johns Hopkins
Plan for reporting unanticipated problems or study deviations.
Study deviations will be reported to IRB
Legal risks such as the risks that would be associated with breach of confidentiality.
Patient confidentiality will be protected by assigning a study identification number and not including any patient identifiers.
Financial risks to the participants.
None
Benefits
Description of the probable benefits for the participant and for society.
An international multicenter registry will enable enrollment of a large number of patients and therefore, a larger sample size to answer the primary and secondary objectives of the study. This will facilitate identification of the patient, lesion and surveillance factors associated with the development of pancreatic cancer in situ or invasive malignancy and in turn, will help us refine surveillance guidelines.
Payment and Remuneration
Detail compensation for participants including possible total compensation, proposed bonus, and any proposed reductions or penalties for not completing the protocol.
None
Costs
Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify who will pay for them.
There are no study costs
JHMIRB eFormA 01
Version 3 Dated: 06/2007
Page PAGE 6 of NUMPAGES 6
Date: ____________________ Principal Investigator: _________________
Application Number: ___________
JHMIRB eFormA 01
Version 3 Dated: 8/15/05
Page PAGE 1 of NUMPAGES 6
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! gd9f sU U U U U U U U U U U U U U U U U U غ hl hUR hU: hvP hQ{ CJ aJ h mH nH u hvP CJ aJ h mH nH u j hW hvP CJ UaJ h hW hvP CJ aJ h hW hvP CJ aJ 2 &P :p : / =!`"#$`% D Lynch1996129(16, 17)1291291217Lynch, H. T.Smyrk, T.Kern, S. E.Hruban, R. H.Lightdale, C. J.Lemon, S. J.Lynch, J. F.Fusaro, L. R.Fusaro, R. M.Ghadirian, P.Creighton University School of Medicine, Department of Preventive Medicine, Omaha, NE 68178, USA.Familial pancreatic cancer: a reviewSemin OncolSemin Oncol251-752321996/04/01Adenomatous Polyposis Coli/geneticsColonic Neoplasms/geneticsGenetic CounselingHumansIncidenceMolecular BiologyMutation/geneticsOncogenes/geneticsPancreatic Neoplasms/diagnosis/drug therapy/*genetics/prevention &control/surgeryPedigreeRectal Neoplasms/geneticsRisk FactorsSmoking/adverse effectsSurvival Rate1996Apr0093-7754 (Print)
0093-7754 (Linking)8623061http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8623061engSchneider201112121212121210117Schneider, R.Slater, E. P.Sina, M.Habbe, N.Fendrich, V.Matthai, E.Langer, P.Bartsch, D. K.Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043 Marburg, Germany.German national case collection for familial pancreatic cancer (FaPaCa): ten years experienceFam CancerFam Cancer323-301022011/01/06AdultAgedAged, 80 and overFemaleGenes, BRCA2GermanyHumansMaleMiddle AgedMutationNuclear Proteins/geneticsPancreatic Neoplasms/*geneticsTumor Suppressor Proteins/genetics2011Jun1573-7292 (Electronic)
1389-9600 (Linking)21207249http://www.ncbi.nlm.nih.gov/pubmed/21207249http://link.springer.com/content/pdf/10.1007%2Fs10689-010-9414-x10.1007/s10689-010-9414-xeng D Lynch1996129(16, 17)1291291217Lynch, H. T.Smyrk, T.Kern, S. E.Hruban, R. H.Lightdale, C. J.Lemon, S. J.Lynch, J. F.Fusaro, L. R.Fusaro, R. M.Ghadirian, P.Creighton University School of Medicine, Department of Preventive Medicine, Omaha, NE 68178, USA.Familial pancreatic cancer: a reviewSemin OncolSemin Oncol251-752321996/04/01Adenomatous Polyposis Coli/geneticsColonic Neoplasms/geneticsGenetic CounselingHumansIncidenceMolecular BiologyMutation/geneticsOncogenes/geneticsPancreatic Neoplasms/diagnosis/drug therapy/*genetics/prevention &control/surgeryPedigreeRectal Neoplasms/geneticsRisk FactorsSmoking/adverse effectsSurvival Rate1996Apr0093-7754 (Print)
0093-7754 (Linking)8623061http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8623061engSchneider201112121212121210117Schneider, R.Slater, E. P.Sina, M.Habbe, N.Fendrich, V.Matthai, E.Langer, P.Bartsch, D. K.Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstrasse, 35043 Marburg, Germany.German national case collection for familial pancreatic cancer (FaPaCa): ten years experienceFam CancerFam Cancer323-301022011/01/06AdultAgedAged, 80 and overFemaleGenes, BRCA2GermanyHumansMaleMiddle AgedMutationNuclear Proteins/geneticsPancreatic Neoplasms/*geneticsTumor Suppressor Proteins/genetics2011Jun1573-7292 (Electronic)
1389-9600 (Linking)21207249http://www.ncbi.nlm.nih.gov/pubmed/21207249http://link.springer.com/content/pdf/10.1007%2Fs10689-010-9414-x10.1007/s10689-010-9414-xeng*\ D Kluijt20091198(18-27)119811988917Kluijt, I.Cats, A.Fockens, P.Nio, Y.Gouma, D. J.Bruno, M. J.Kluijt, I., Family Cancer Clinic, The Netherlands Cancer Institute, 1066 CX Amsterdam, NetherlandsAtypical familial presentation of FAMMM syndrome with a high incidence of pancreatic cancer: Case finding of asymptomatic individuals by EUS surveillanceJ Clin GastroenterolJ Clin Gastroenterol853-857439cyclin dependent kinase inhibitor 2Aadultagedarticlecancer epidemiologycancer mortalitycancer screeningcancer surgerycase findingclinical articlecomputer assisted tomographydisease markerdisease surveillanceearly interventionendometriosisendoscopic echographyfamilial atypical multiple mole melanoma syndromefamilyfemalegene mutationheterozygotehigh risk populationhistologyhumanhuman tissueincidenceintraductal papillary mucinous tumormalemalignant lentigomelanomaNetherlandsnuclear magnetic resonance imagingovariectomypancreas adenocarcinomapancreas resectionphenotypeprecancerpriority journalprostate cancerskin carcinomavalvular heart diseasevon Willebrand disease20090192-0790http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L355376596http://dx.doi.org/10.1097/MCG.0b013e3181981123http://graphics.tx.ovid.com/ovftpdfs/FPDDNCIBAEBJHJ00/fs046/ovft/live/gv023/00004836/00004836-200910000-00011.pdfOlson20131083108310833917Olson, S. H.Kurtz, R. C.Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. olsons@mskcc.orgEpidemiology of pancreatic cancer and the role of family historyJ Surg OncolJ Surg Oncol1-710712012/05/17Aged*Family HealthFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleNeoplastic Syndromes, Hereditary/epidemiologyPancreatic Neoplasms/*epidemiology/*genetics/prevention & controlRisk FactorsUnited States/epidemiology2013Jan1096-9098 (Electronic)
0022-4790 (Linking)22589078http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22589078http://onlinelibrary.wiley.com/store/10.1002/jso.23149/asset/23149_ftp.pdf?v=1&t=he8ckff1&s=c298964cae3d9143c258b047b2b703385ca06d1710.1002/jso.23149engIqbal20121085108510854017Iqbal, J.Ragone, A.Lubinski, J.Lynch, H. T.Moller, P.Ghadirian, P.Foulkes, W. D.Armel, S.Eisen, A.Neuhausen, S. L.Senter, L.Singer, C. F.Ainsworth, P.Kim-Sing, C.Tung, N.Friedman, E.Llacuachaqui, M.Ping, S.Narod, S. A.Women's College Research Institute, Familial Breast Cancer Research, 790 Bay Street, Toronto, Ontario, Canada M5G 1N8.The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriersBr J CancerBr J Cancer2005-9107122012/10/27AdultAgedBRCA1 Protein/*geneticsBRCA2 Protein/*geneticsCohort StudiesFemale*Genes, BRCA1*Genes, BRCA2*Germ-Line Mutation*HeterozygoteHumansIncidenceKaplan-Meier EstimateMiddle AgedPancreatic Neoplasms/*epidemiology/*genetics/mortality2012Dec 41532-1827 (Electronic)
0007-0920 (Linking)23099806http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23099806http://www.nature.com/bjc/journal/v107/n12/pdf/bjc2012483a.pdf3516682bjc2012483 [pii]
10.1038/bjc.2012.483engJones20091090109010904117Jones, S.Hruban, R. H.Kamiyama, M.Borges, M.Zhang, X.Parsons, D. W.Lin, J. C.Palmisano, E.Brune, K.Jaffee, E. M.Iacobuzio-Donahue, C. A.Maitra, A.Parmigiani, G.Kern, S. E.Velculescu, V. E.Kinzler, K. W.Vogelstein, B.Eshleman, J. R.Goggins, M.Klein, A. P.Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Baltimore, MD 21231, USA.Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility geneScienceScience21732459242009/03/07Breast Neoplasms/geneticsCodon, TerminatorFemale*Genetic Predisposition to Disease*Germ-Line MutationHumansMaleNuclear Proteins/*geneticsPancreatic Neoplasms/*geneticsPedigreeSequence Analysis, DNASequence DeletionTumor Suppressor Proteins/*genetics2009Apr 101095-9203 (Electronic)
0036-8075 (Linking)19264984http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19264984http://www.sciencemag.org/content/324/5924/217.full.pdf26843321171202 [pii]
10.1126/science.1171202engKastrinos20091091109110914217Kastrinos, F.Mukherjee, B.Tayob, N.Wang, F.Sparr, J.Raymond, V. M.Bandipalliam, P.Stoffel, E. M.Gruber, S. B.Syngal, S.Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.Risk of pancreatic cancer in families with Lynch syndromeJAMAJAMA1790-5302162009/10/29Adaptor Proteins, Signal Transducing/*geneticsAdultAgedAged, 80 and overColorectal Neoplasms, Hereditary Nonpolyposis/epidemiology/*geneticsDNA Mismatch Repair/*geneticsDNA Mutational AnalysisDNA-Binding Proteins/*geneticsFemaleGenotypeGerm-Line MutationHumansMaleMiddle AgedMutS Homolog 2 Protein/*geneticsNuclear Proteins/*geneticsPancreatic Neoplasms/epidemiology/*geneticsPedigreePhenotypeProportional Hazards ModelsRegistriesRiskSEER ProgramYoung Adult2009Oct 281538-3598 (Electronic)
0098-7484 (Linking)19861671http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19861671http://jama.jamanetwork.com/data/Journals/JAMA/4485/joc90115_1790_1795.pdf302/16/1790 [pii]
10.1001/jama.2009.1529engde Snoo20081094109410944317de Snoo, F. A.Bishop, D. T.Bergman, W.van Leeuwen, I.van der Drift, C.van Nieuwpoort, F. A.Out-Luiting, C. J.Vasen, H. F.ter Huurne, J. A.Frants, R. R.Willemze, R.Breuning, M. H.Gruis, N. A.Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma familiesClin Cancer ResClin Cancer Res7151-714212008/11/05FemaleFounder Effect*Genes, p16*Genetic Predisposition to DiseaseHumansMaleMelanoma/*geneticsMultiple Endocrine Neoplasia/*epidemiology*MutationRisk AssessmentSkin Neoplasms/*genetics2008Nov 11078-0432 (Print)
1078-0432 (Linking)18981015http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18981015http://clincancerres.aacrjournals.org/content/14/21/7151.full.pdf14/21/7151 [pii]
10.1158/1078-0432.CCR-08-0403engKorsse20131097109710974417Korsse, S. E.Harinck, F.van Lier, M. G.Biermann, K.Offerhaus, G. J.Krak, N.Looman, C. W.van Veelen, W.Kuipers, E. J.Wagner, A.Dekker, E.Mathus-Vliegen, E. M.Fockens, P.van Leerdam, M. E.Bruno, M. J.Department of Gastroenterology & Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. s.korsse@erasmusmc.nlPancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillanceJ Med GenetJ Med Genet59-645012012/12/152013Jan1468-6244 (Electronic)
0022-2593 (Linking)23240097http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23240097http://jmg.bmj.com/content/50/1/59.full.pdfjmedgenet-2012-101277 [pii]
10.1136/jmedgenet-2012-101277engGiardiello19931107110711074517Giardiello, F. M.Offerhaus, G. J.Lee, D. H.Krush, A. J.Tersmette, A. C.Booker, S. V.Kelley, N. C.Hamilton, S. R.Department of Medicine, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland 21205.Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposisGutGut1394-634101993/10/01Adenocarcinoma*Adenomatous Polyposis Coli/complicationsAdolescentAdultAgedFemaleHumansMaleMiddle Aged*Neoplasms, Multiple Primary*Pancreatic Neoplasms/complicationsRisk Factors*Thyroid Neoplasms/complications1993Oct0017-5749 (Print)
0017-5749 (Linking)8244108http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8244108http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1374548/pdf/gut00561-0122.pdf1374548engRebours20081111111111114617Rebours, V.Boutron-Ruault, M. C.Schnee, M.Ferec, C.Maire, F.Hammel, P.Ruszniewski, P.Levy, P.Pole des Maladies de l'Appareil Digestif, Service de Gastroenterologie - Pancreatologie, Hopital Beaujon, AP-HP, Universite Denis Diderot-Paris VII, Clichy, France.Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive seriesAm J GastroenterolAm J Gastroenterol111-910312008/01/11Adenocarcinoma/*epidemiology/etiology/pathologyAdolescentAdultAgedAged, 80 and overChildChild, PreschoolDNA/*geneticsFemaleFrance/epidemiologyGenetic Predisposition to DiseaseHumansIncidenceInfantMaleMiddle Aged*MutationPancreatic Neoplasms/*epidemiology/etiology/pathologyPancreatitis/complications/*geneticsRisk FactorsTrypsinTrypsinogen/*genetics2008Jan0002-9270 (Print)
0002-9270 (Linking)18184119http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18184119http://www.nature.com/ajg/journal/v103/n1/pdf/ajg20085018a.pdfAJG1597 [pii]
10.1111/j.1572-0241.2007.01597.xengRuijs20101112111211124717Ruijs, M. W.Verhoef, S.Rookus, M. A.Pruntel, R.van der Hout, A. H.Hogervorst, F. B.Kluijt, I.Sijmons, R. H.Aalfs, C. M.Wagner, A.Ausems, M. G.Hoogerbrugge, N.van Asperen, C. J.Gomez Garcia, E. B.Meijers-Heijboer, H.Ten Kate, L. P.Menko, F. H.van 't Veer, L. J.Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands.TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypesJ Med GenetJ Med Genet421-84762010/06/05AdultColonic Neoplasms/diagnosis/geneticsDNA Mutational AnalysisFamily HealthFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic Testing/methodsGenotype*Germ-Line MutationHumansLi-Fraumeni Syndrome/diagnosis/*geneticsMaleMiddle AgedNeoplasms/diagnosis/*geneticsNetherlandsPancreatic Neoplasms/diagnosis/geneticsPhenotypeRisk FactorsTumor Suppressor Protein p53/*geneticsYoung Adult2010Jun1468-6244 (Electronic)
0022-2593 (Linking)20522432http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20522432http://jmg.bmj.com/content/47/6/421.full.pdf47/6/421 [pii]
10.1136/jmg.2009.073429eng *\ D Kluijt20091198(18-27)119811988917Kluijt, I.Cats, A.Fockens, P.Nio, Y.Gouma, D. J.Bruno, M. J.Kluijt, I., Family Cancer Clinic, The Netherlands Cancer Institute, 1066 CX Amsterdam, NetherlandsAtypical familial presentation of FAMMM syndrome with a high incidence of pancreatic cancer: Case finding of asymptomatic individuals by EUS surveillanceJ Clin GastroenterolJ Clin Gastroenterol853-857439cyclin dependent kinase inhibitor 2Aadultagedarticlecancer epidemiologycancer mortalitycancer screeningcancer surgerycase findingclinical articlecomputer assisted tomographydisease markerdisease surveillanceearly interventionendometriosisendoscopic echographyfamilial atypical multiple mole melanoma syndromefamilyfemalegene mutationheterozygotehigh risk populationhistologyhumanhuman tissueincidenceintraductal papillary mucinous tumormalemalignant lentigomelanomaNetherlandsnuclear magnetic resonance imagingovariectomypancreas adenocarcinomapancreas resectionphenotypeprecancerpriority journalprostate cancerskin carcinomavalvular heart diseasevon Willebrand disease20090192-0790http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L355376596http://dx.doi.org/10.1097/MCG.0b013e3181981123http://graphics.tx.ovid.com/ovftpdfs/FPDDNCIBAEBJHJ00/fs046/ovft/live/gv023/00004836/00004836-200910000-00011.pdfOlson20131083108310833917Olson, S. H.Kurtz, R. C.Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. olsons@mskcc.orgEpidemiology of pancreatic cancer and the role of family historyJ Surg OncolJ Surg Oncol1-710712012/05/17Aged*Family HealthFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleNeoplastic Syndromes, Hereditary/epidemiologyPancreatic Neoplasms/*epidemiology/*genetics/prevention & controlRisk FactorsUnited States/epidemiology2013Jan1096-9098 (Electronic)
0022-4790 (Linking)22589078http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22589078http://onlinelibrary.wiley.com/store/10.1002/jso.23149/asset/23149_ftp.pdf?v=1&t=he8ckff1&s=c298964cae3d9143c258b047b2b703385ca06d1710.1002/jso.23149engIqbal20121085108510854017Iqbal, J.Ragone, A.Lubinski, J.Lynch, H. T.Moller, P.Ghadirian, P.Foulkes, W. D.Armel, S.Eisen, A.Neuhausen, S. L.Senter, L.Singer, C. F.Ainsworth, P.Kim-Sing, C.Tung, N.Friedman, E.Llacuachaqui, M.Ping, S.Narod, S. A.Women's College Research Institute, Familial Breast Cancer Research, 790 Bay Street, Toronto, Ontario, Canada M5G 1N8.The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriersBr J CancerBr J Cancer2005-9107122012/10/27AdultAgedBRCA1 Protein/*geneticsBRCA2 Protein/*geneticsCohort StudiesFemale*Genes, BRCA1*Genes, BRCA2*Germ-Line Mutation*HeterozygoteHumansIncidenceKaplan-Meier EstimateMiddle AgedPancreatic Neoplasms/*epidemiology/*genetics/mortality2012Dec 41532-1827 (Electronic)
0007-0920 (Linking)23099806http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23099806http://www.nature.com/bjc/journal/v107/n12/pdf/bjc2012483a.pdf3516682bjc2012483 [pii]
10.1038/bjc.2012.483engJones20091090109010904117Jones, S.Hruban, R. H.Kamiyama, M.Borges, M.Zhang, X.Parsons, D. W.Lin, J. C.Palmisano, E.Brune, K.Jaffee, E. M.Iacobuzio-Donahue, C. A.Maitra, A.Parmigiani, G.Kern, S. E.Velculescu, V. E.Kinzler, K. W.Vogelstein, B.Eshleman, J. R.Goggins, M.Klein, A. P.Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Baltimore, MD 21231, USA.Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility geneScienceScience21732459242009/03/07Breast Neoplasms/geneticsCodon, TerminatorFemale*Genetic Predisposition to Disease*Germ-Line MutationHumansMaleNuclear Proteins/*geneticsPancreatic Neoplasms/*geneticsPedigreeSequence Analysis, DNASequence DeletionTumor Suppressor Proteins/*genetics2009Apr 101095-9203 (Electronic)
0036-8075 (Linking)19264984http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19264984http://www.sciencemag.org/content/324/5924/217.full.pdf26843321171202 [pii]
10.1126/science.1171202engKastrinos20091091109110914217Kastrinos, F.Mukherjee, B.Tayob, N.Wang, F.Sparr, J.Raymond, V. M.Bandipalliam, P.Stoffel, E. M.Gruber, S. B.Syngal, S.Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.Risk of pancreatic cancer in families with Lynch syndromeJAMAJAMA1790-5302162009/10/29Adaptor Proteins, Signal Transducing/*geneticsAdultAgedAged, 80 and overColorectal Neoplasms, Hereditary Nonpolyposis/epidemiology/*geneticsDNA Mismatch Repair/*geneticsDNA Mutational AnalysisDNA-Binding Proteins/*geneticsFemaleGenotypeGerm-Line MutationHumansMaleMiddle AgedMutS Homolog 2 Protein/*geneticsNuclear Proteins/*geneticsPancreatic Neoplasms/epidemiology/*geneticsPedigreePhenotypeProportional Hazards ModelsRegistriesRiskSEER ProgramYoung Adult2009Oct 281538-3598 (Electronic)
0098-7484 (Linking)19861671http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19861671http://jama.jamanetwork.com/data/Journals/JAMA/4485/joc90115_1790_1795.pdf302/16/1790 [pii]
10.1001/jama.2009.1529engde Snoo20081094109410944317de Snoo, F. A.Bishop, D. T.Bergman, W.van Leeuwen, I.van der Drift, C.van Nieuwpoort, F. A.Out-Luiting, C. J.Vasen, H. F.ter Huurne, J. A.Frants, R. R.Willemze, R.Breuning, M. H.Gruis, N. A.Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma familiesClin Cancer ResClin Cancer Res7151-714212008/11/05FemaleFounder Effect*Genes, p16*Genetic Predisposition to DiseaseHumansMaleMelanoma/*geneticsMultiple Endocrine Neoplasia/*epidemiology*MutationRisk AssessmentSkin Neoplasms/*genetics2008Nov 11078-0432 (Print)
1078-0432 (Linking)18981015http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18981015http://clincancerres.aacrjournals.org/content/14/21/7151.full.pdf14/21/7151 [pii]
10.1158/1078-0432.CCR-08-0403engKorsse20131097109710974417Korsse, S. E.Harinck, F.van Lier, M. G.Biermann, K.Offerhaus, G. J.Krak, N.Looman, C. W.van Veelen, W.Kuipers, E. J.Wagner, A.Dekker, E.Mathus-Vliegen, E. M.Fockens, P.van Leerdam, M. E.Bruno, M. J.Department of Gastroenterology & Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. s.korsse@erasmusmc.nlPancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillanceJ Med GenetJ Med Genet59-645012012/12/152013Jan1468-6244 (Electronic)
0022-2593 (Linking)23240097http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23240097http://jmg.bmj.com/content/50/1/59.full.pdfjmedgenet-2012-101277 [pii]
10.1136/jmedgenet-2012-101277engGiardiello19931107110711074517Giardiello, F. M.Offerhaus, G. J.Lee, D. H.Krush, A. J.Tersmette, A. C.Booker, S. V.Kelley, N. C.Hamilton, S. R.Department of Medicine, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland 21205.Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposisGutGut1394-634101993/10/01Adenocarcinoma*Adenomatous Polyposis Coli/complicationsAdolescentAdultAgedFemaleHumansMaleMiddle Aged*Neoplasms, Multiple Primary*Pancreatic Neoplasms/complicationsRisk Factors*Thyroid Neoplasms/complications1993Oct0017-5749 (Print)
0017-5749 (Linking)8244108http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8244108http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1374548/pdf/gut00561-0122.pdf1374548engRebours20081111111111114617Rebours, V.Boutron-Ruault, M. C.Schnee, M.Ferec, C.Maire, F.Hammel, P.Ruszniewski, P.Levy, P.Pole des Maladies de l'Appareil Digestif, Service de Gastroenterologie - Pancreatologie, Hopital Beaujon, AP-HP, Universite Denis Diderot-Paris VII, Clichy, France.Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive seriesAm J GastroenterolAm J Gastroenterol111-910312008/01/11Adenocarcinoma/*epidemiology/etiology/pathologyAdolescentAdultAgedAged, 80 and overChildChild, PreschoolDNA/*geneticsFemaleFrance/epidemiologyGenetic Predisposition to DiseaseHumansIncidenceInfantMaleMiddle Aged*MutationPancreatic Neoplasms/*epidemiology/etiology/pathologyPancreatitis/complications/*geneticsRisk FactorsTrypsinTrypsinogen/*genetics2008Jan0002-9270 (Print)
0002-9270 (Linking)18184119http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18184119http://www.nature.com/ajg/journal/v103/n1/pdf/ajg20085018a.pdfAJG1597 [pii]
10.1111/j.1572-0241.2007.01597.xengRuijs20101112111211124717Ruijs, M. W.Verhoef, S.Rookus, M. A.Pruntel, R.van der Hout, A. H.Hogervorst, F. B.Kluijt, I.Sijmons, R. H.Aalfs, C. M.Wagner, A.Ausems, M. G.Hoogerbrugge, N.van Asperen, C. J.Gomez Garcia, E. B.Meijers-Heijboer, H.Ten Kate, L. P.Menko, F. H.van 't Veer, L. J.Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands.TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypesJ Med GenetJ Med Genet421-84762010/06/05AdultColonic Neoplasms/diagnosis/geneticsDNA Mutational AnalysisFamily HealthFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic Testing/methodsGenotype*Germ-Line MutationHumansLi-Fraumeni Syndrome/diagnosis/*geneticsMaleMiddle AgedNeoplasms/diagnosis/*geneticsNetherlandsPancreatic Neoplasms/diagnosis/geneticsPhenotypeRisk FactorsTumor Suppressor Protein p53/*geneticsYoung Adult2010Jun1468-6244 (Electronic)
0022-2593 (Linking)20522432http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20522432http://jmg.bmj.com/content/47/6/421.full.pdf47/6/421 [pii]
10.1136/jmg.2009.073429eng $$If !v h#v #v8 #v :V l
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t 0 65 5M5/ / / / / p yt) D Brune20101066(29)106610663017Brune, K. A.Lau, B.Palmisano, E.Canto, M.Goggins, M. G.Hruban, R. H.Klein, A. P.Department of Pathology, Sol Goldman Pancreatic Cancer Research Center at Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.Importance of age of onset in pancreatic cancer kindredsJ Natl Cancer InstJ Natl Cancer Inst119-2610222010/01/14AdultAge of OnsetAgedFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleMiddle AgedOdds RatioPancreatic Neoplasms/*diagnosis/*epidemiology/geneticsSEER ProgramUnited States/epidemiology2010Jan 201460-2105 (Electronic)
0027-8874 (Linking)20068195http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20068195http://jnci.oxfordjournals.org/content/102/2/119.full.pdf2808346djp466 [pii]
10.1093/jnci/djp466eng D Brune20101066(29)106610663017Brune, K. A.Lau, B.Palmisano, E.Canto, M.Goggins, M. G.Hruban, R. H.Klein, A. P.Department of Pathology, Sol Goldman Pancreatic Cancer Research Center at Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.Importance of age of onset in pancreatic cancer kindredsJ Natl Cancer InstJ Natl Cancer Inst119-2610222010/01/14AdultAge of OnsetAgedFemaleGenetic Predisposition to DiseaseHumansIncidenceMaleMiddle AgedOdds RatioPancreatic Neoplasms/*diagnosis/*epidemiology/geneticsSEER ProgramUnited States/epidemiology2010Jan 201460-2105 (Electronic)
0027-8874 (Linking)20068195http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20068195http://jnci.oxfordjournals.org/content/102/2/119.full.pdf2808346djp466 [pii]
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