2021
A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer
Jermusyk A, Zhong J, Connelly KE, Gordon N, Perera S, Abdolalizadeh E, Zhang T, O’Brien A, Hoskins JW, Collins I, Eiser D, Yuan C, Consortium P, Consortium P, Albanes D, Arslan A, Gurrea A, Beane-Freeman L, Bracci P, Bueno-de-Mesquita B, Buring J, Canzian F, Gallinger S, Gaziano J, Giles G, Goodman P, Johansson M, Kooperberg C, LeMarchand L, Malats N, Neale R, Panico S, Peters U, Real F, Shu X, Sund M, Thornquist M, Tjønneland A, Travis R, Van Den Eeden S, Visvanathan K, Zheng W, Kraft P, Risch H, Jacobs E, Li D, Du M, Stolzenberg-Solomon R, Klein A, Smith J, Wolpin B, Chanock S, Shi J, Petersen G, Westlake C, Amundadottir L. A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer. American Journal Of Human Genetics 2021, 108: 1852-1865. PMID: 34559995, PMCID: PMC8546220, DOI: 10.1016/j.ajhg.2021.09.002.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesB2 proteinEndoplasmic reticulumDeletion allelePremature stop codonHuman genomeGWAS datasetsSuch lociRisk lociAssociation studiesStop codonER stressCTRB2Pancreatic ductal adenocarcinomaBp deletionExon 6European ancestryLociExon 7Intracellular accumulationExon 5ProteinGermline variantsChymotrypsin activityAlleles
2020
Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk
Zhu J, Shu X, Guo X, Liu D, Bao J, Milne RL, Giles GG, Wu C, Du M, White E, Risch HA, Malats N, Duell EJ, Goodman PJ, Li D, Bracci P, Katzke V, Neale RE, Gallinger S, Van Den Eeden SK, Arslan AA, Canzian F, Kooperberg C, Freeman L, Scelo G, Visvanathan K, Haiman CA, Le Marchand L, Yu H, Petersen GM, Stolzenberg-Solomon R, Klein AP, Cai Q, Long J, Shu XO, Zheng W, Wu L. Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk. Cancer Epidemiology Biomarkers & Prevention 2020, 29: 1501-1508. PMID: 32439797, PMCID: PMC7334065, DOI: 10.1158/1055-9965.epi-20-0091.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaProtein quantitative trait lociQuantitative trait lociRisk variantsBlood protein biomarkersPathway enrichment analysisPotential target genesCancer-related pathwaysPDAC riskProtein biomarkersTrait lociTarget genesPancreatic Cancer Case-Control ConsortiumPancreatic Cancer Cohort ConsortiumEnrichment analysisProteinGenetic instrumentsPancreatic cancer riskProtein levelsGenesPDAC developmentProtein biomarker candidatesRisk factorsDuctal adenocarcinomaLethal malignancyHepcidin-regulating Iron-metabolism Genes and Pancreatic Ductal Adenocarcinoma: A Pathway Analysis of Genome-wide Association Studies
Julián-Serrano S, Yuan F, Benyamin B, Wheeler W, Amundadottir L, Jacobs E, Kraft P, Li D, Petersen G, Risch H, Wolpin B, Yu K, Klein A, Stolzenberg-Solomon R. Hepcidin-regulating Iron-metabolism Genes and Pancreatic Ductal Adenocarcinoma: A Pathway Analysis of Genome-wide Association Studies. Cancer Epidemiology Biomarkers & Prevention 2020, 29: 692-692. DOI: 10.1158/1055-9965.epi-20-0056.Peer-Reviewed Original ResearchSingle nucleotide polymorphismsAssociation studiesSNP-level associationsGenome-wide association studiesAssociated single-nucleotide polymorphismsAdjacent genomic regionsWide association studyPrevious GWAS studiesIron metabolism genesIron metabolismGenomic regionsTfR1 genePancreatic ductal adenocarcinomaGWAS studiesPancreatic Cancer Case-Control ConsortiumPathway associationsPathway analysisGenesGenetic susceptibilityAdaptive rankRare mutationsAbstract Pancreatic ductal adenocarcinomaCommon variantsPathwayPotential role
2019
Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer
Xiao Y, Yang H, Lu J, Li D, Xu C, Risch HA. Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer. BMC Cancer 2019, 19: 1020. PMID: 31664937, PMCID: PMC6819453, DOI: 10.1186/s12885-019-6250-8.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaMetastatic pancreatic ductal adenocarcinomaOverall survivalSerum GGTSignificant dose-response associationCox proportional hazards modelMetastatic PDAC patientsDose-response associationMetastatic pancreatic cancerPancreatic cancer survivalSpecialized cancer hospitalBlood glucose levelsProportional hazards modelHazard ratioPrognostic roleCancer HospitalPDAC patientsCancer survivalSubgroup analysisPancreatic cancerDuctal adenocarcinomaMetastatic PCCancer occurrenceGlucose levelsMortality riskDo changes in health reveal the possibility of undiagnosed pancreatic cancer? Development of a risk-prediction model based on healthcare claims data
Baecker A, Kim S, Risch HA, Nuckols TK, Wu BU, Hendifar AE, Pandol SJ, Pisegna JR, Jeon CY. Do changes in health reveal the possibility of undiagnosed pancreatic cancer? Development of a risk-prediction model based on healthcare claims data. PLOS ONE 2019, 14: e0218580. PMID: 31237889, PMCID: PMC6592596, DOI: 10.1371/journal.pone.0218580.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancerRisk factorsPDAC diagnosisNew-onset diabetes patientsEnd Results (SEER) tumorMonths of claimsUndiagnosed pancreatic cancerClinical risk factorsMultivariable logistic regressionDiagnosis of PDACSex-matched controlsCase-control studyRisk prediction modelHealthcare claims dataSurveillance EpidemiologyResults TumorsDiabetes patientsDuctal adenocarcinomaClaims dataHealthcare claimsEarly detection methodsLogistic regressionCancerDiagnosisA Pathway Analysis of Hereditary Hemochromatosis-related Genes and Pancreatic Ductal Adenocarcinoma Risk (FS11-05-19)
Julián-Serrano S, Yu K, Yuan F, Wheeler W, Karimi P, Amundadottir L, Jacobs E, Kraft P, Li D, Petersen G, Risch H, Wolphin B, Klein A, Stolzenberg-Solomon R. A Pathway Analysis of Hereditary Hemochromatosis-related Genes and Pancreatic Ductal Adenocarcinoma Risk (FS11-05-19). Current Developments In Nutrition 2019, 3: nzz037.fs11-05-19. PMCID: PMC6573995, DOI: 10.1093/cdn/nzz037.fs11-05-19.Peer-Reviewed Original ResearchPancreatic ductal adenocarcinomaHereditary hemochromatosis geneGenetic susceptibilityPDAC riskSingle nucleotide polymorphismsHereditary hemochromatosisHigh red meat intakeType 2 diabetes mellitusHemochromatosis geneRed meat intakePancreatic Cancer Case-Control ConsortiumIron-rich foodsType 2 diabetesPancreatic Cancer Cohort ConsortiumPancreatic ductal adenocarcinoma (PDAC) riskIntramural Research ProgramNational Cancer InstitutePathway analysisDiabetes mellitusAdenocarcinoma riskPrimary hemochromatosisRisk factorsChronic diseasesDuctal adenocarcinomaMeat intakeCurrent Approaches to Pancreatic Cancer Screening
Chhoda A, Lu L, Clerkin BM, Risch H, Farrell JJ. Current Approaches to Pancreatic Cancer Screening. American Journal Of Pathology 2019, 189: 22-35. PMID: 30558719, DOI: 10.1016/j.ajpath.2018.09.013.BooksConceptsPancreatic ductal adenocarcinomaHigh-risk individualsRisk factorsCancer syndromesHereditary breast-ovarian cancer syndromeBreast-ovarian cancer syndromeEarly resectable stagePancreatic cancer screeningScreening strategyFamilial atypical multipleCancer-related deathOvarian cancer syndromeCurrent screening strategiesLi-Fraumeni syndromePeutz-Jeghers syndromeGenetic risk factorsResectable stageCancer screeningPancreatic cancerChronic diseasesDuctal adenocarcinomaLynch syndromePrecursor lesionsLower incidenceFamilial history
2018
Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
Walsh N, Zhang H, Hyland PL, Yang Q, Mocci E, Zhang M, Childs EJ, Collins I, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Brennan P, Canzian F, Duell EJ, Gallinger S, Giles GG, Goggins M, Goodman GE, Goodman PJ, Hung RJ, Kooperberg C, Kurtz RC, Malats N, LeMarchand L, Neale RE, Olson SH, Scelo G, Shu XO, Van Den Eeden SK, Visvanathan K, White E, Zheng W, consortia P, Albanes D, Andreotti G, Babic A, Bamlet W, Berndt S, Borgida A, Boutron-Ruault M, Brais L, Brennan P, Bueno-de-Mesquita B, Buring J, Chaffee K, Chanock S, Cleary S, Cotterchio M, Foretova L, Fuchs C, Gaziano J, Giovannucci E, Goggins M, Hackert T, Haiman C, Hartge P, Hasan M, Helzlsouer K, Herman J, Holcatova I, Holly E, Hoover R, Hung R, Janout V, Klein E, Kurtz R, Laheru D, Lee I, Lu L, Malats N, Mannisto S, Milne R, Oberg A, Orlow I, Patel A, Peters U, Porta M, Real F, Rothman N, Sesso H, Severi G, Silverman D, Strobel O, Sund M, Thornquist M, Tobias G, Wactawski-Wende J, Wareham N, Weiderpass E, Wentzensen N, Wheeler W, Yu H, Zeleniuch-Jacquotte A, Kraft P, Li D, Jacobs E, Petersen G, Wolpin B, Risch H, Amundadottir L, Yu K, Klein A, Stolzenberg-Solomon R. Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer. Journal Of The National Cancer Institute 2018, 111: 557-567. PMID: 30541042, PMCID: PMC6579744, DOI: 10.1093/jnci/djy155.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGene setsSingle nucleotide polymorphismsFunctional annotationEpidermal growth factor receptor transactivationExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisGrowth factor receptor transactivationTop single nucleotide polymorphismsG protein-coupled receptorsGene-set analysisProtein-coupled receptorsIndividual single nucleotide polymorphismsBeta-cell developmentEQTL analysisGWAS dataPCC genesPancreatic ductal adenocarcinomaReceptor transactivationLocus analysisPathway analysisAssociation studiesGenesSusceptibility genesIdentifies associations
2015
Urinary Prostaglandin E2 Metabolite and Pancreatic Cancer Risk: Case-Control Study in Urban Shanghai
Zhao J, Wang J, Du J, Xu H, Zhang W, Ni QX, Yu H, Risch HA, Gao YT, Gao Y. Urinary Prostaglandin E2 Metabolite and Pancreatic Cancer Risk: Case-Control Study in Urban Shanghai. PLOS ONE 2015, 10: e0118004. PMID: 25679523, PMCID: PMC4332509, DOI: 10.1371/journal.pone.0118004.Peer-Reviewed Original ResearchConceptsCase-control studyPancreatic cancer riskPancreatic cancerOdds ratioCancer riskRecent population-based case-control studiesPopulation-based case-control studyUrinary PGE-M levelsUrinary prostaglandin E2 metabolitePGE-M levelsProstaglandin E2 metaboliteProstaglandin E2 metabolite levelsHigh meat intakePancreatic ductal adenocarcinoma casesUnconditional logistic regressionCOX-2 pathwayConfidence intervalsPancreatic ductal adenocarcinomaUrinary PGEDiabetes historyThird tertileE2 metaboliteDuctal adenocarcinomaMeat intakeAdenocarcinoma cases
2013
Re-evaluation of ABO gene polymorphisms detected in a genome-wide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population
Xu HL, Cheng JR, Zhang W, Wang J, Yu H, Ni QX, Risch HA, Gao YT. Re-evaluation of ABO gene polymorphisms detected in a genome-wide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population. Cancer Communications 2013, 33: 68-73. PMID: 23816557, PMCID: PMC3884064, DOI: 10.5732/cjc.013.10060.Peer-Reviewed Original ResearchConceptsRisk of PDACPancreatic ductal adenocarcinomaCancer riskDuctal adenocarcinomaPopulation-based case-control studyChinese populationCase-control studyPancreatic cancer riskSignificant gene-environment interactionElevated cancer riskFatal malignancyPancreatic cancerTT carriersHealthy controlsGene-environment interactionsGene polymorphismsT alleleC alleleABO variantsWide association studyAssociation studiesMultifactor dimensionality reduction methodAdenocarcinomaRiskABO alleles