2021
Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis
Ong J, An J, Han X, Law M, Nandakumar P, team 2, consortium E, Schumacher J, Gockel I, Bohmer A, Jankowski J, Palles C, Olsen C, Neale R, Fitzgerald R, Thrift A, Vaughan T, Buas M, Hinds D, Gharahkhani P, Kendall B, MacGregor S, consortium E, Fitzgerald R, Buas M, Gammon M, Corley D, Shaheen N, Hardie L, Bird N, Reid B, Chow W, Risch H, Ye W, Liu G, Romero Y, Bernstein L, Wu A, Schumacher J, Gockel I, Bohmer A, Jankowski J, Palles C, Whiteman D, team 2, Agee M, Aslibekyan S, Auton A, Bell R, Bryc K, Clark S, Elson S, Fletez-Brant K, Fontanillas P, Furlotte N, Gandhi P, Heilbron K, Hicks B, Hinds D, Huber K, Jewett E, Jiang Y, Kleinman A, Lin K, Litterman N, Luff M, McCreight J, McIntyre M, McManus K, Mountain J, Mozaffari S, Nandakumar P, Noblin E, Northover C, O'Connell J, Petrakovitz A, Pitts S, Poznik G, Sathirapongsasuti J, Shastri A, Shelton J, Shringarpure S, Tian C, Tung J, Tunney R, Vacic V, Wang X, Zare A. Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis. Gut 2021, 71: 1053-1061. PMID: 34187846, PMCID: PMC9120377, DOI: 10.1136/gutjnl-2020-323906.Peer-Reviewed Original ResearchMeSH KeywordsBarrett EsophagusEsophageal NeoplasmsEsophagitis, PepticGastroesophageal RefluxGenome-Wide Association StudyHumansObesity
2019
Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus
Xie SH, Fang R, Huang M, Dai J, Thrift AP, Anderson LA, Chow WH, Bernstein L, Gammon MD, Risch HA, Shaheen NJ, Reid BJ, Wu AH, Iyer PG, Liu G, Corley DA, Whiteman DC, Caldas C, Pharoah PD, Hardie LJ, Fitzgerald RC, Shen H, Vaughan TL, Lagergren J. Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus. Clinical Gastroenterology And Hepatology 2019, 18: 2701-2709.e3. PMID: 31756444, PMCID: PMC7580878, DOI: 10.1016/j.cgh.2019.11.030.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBarrett EsophagusEsophageal NeoplasmsFemaleGenome-Wide Association StudyGonadal Steroid HormonesHumansMaleRisk FactorsConceptsRisk of BERisk of EACBarrett's esophagusMendelian randomization analysisSex hormonesOdds ratioRandomization analysisSex hormone-binding globulinSpecific sex hormonesFree androgen indexFollicle-stimulating hormoneHormone-binding globulinGenetic risk scoreAndrogen indexDecreased riskEsophageal adenocarcinomaRisk scoreEsophagusAbstractTextLogistic regressionHormoneClear associationControl participantsGenetic factorsWomenNo Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study
Dong J, Gharahkhani P, Chow WH, Gammon MD, Liu G, Caldas C, Wu AH, Ye W, Onstad L, Anderson LA, Bernstein L, Pharoah PD, Risch HA, Corley DA, Fitzgerald RC, Consortium S, Iyer PG, Reid BJ, Lagergren J, Shaheen NJ, Vaughan TL, MacGregor S, Love S, Palles C, Tomlinson I, Gockel I, May A, Gerges C, Anders M, Böhmer AC, Becker J, Kreuser N, Thieme R, Noder T, Venerito M, Veits L, Schmidt T, Schmidt C, Izbicki JR, Hölscher AH, Lang H, Lorenz D, Schumacher B, Mayershofer R, Vashist Y, Ott K, Vieth M, Weismüller J, Nöthen MM, Moebus S, Knapp M, Peters WHM, Neuhaus H, Rösch T, Ell C, Jankowski J, Schumacher J, Neale RE, Whiteman DC, Thrift AP. No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study. Clinical Gastroenterology And Hepatology 2019, 17: 2227-2235.e1. PMID: 30716477, PMCID: PMC6675666, DOI: 10.1016/j.cgh.2019.01.041.Peer-Reviewed Original ResearchConceptsRisk of BEMendelian randomization studyBarrett's esophagusEsophageal adenocarcinomaInverse variance weightingRandomization studyRisk of EACHydroxy vitamin DVitamin D statusVariance weightingEsophageal Adenocarcinoma ConsortiumD statusEAC riskVitamin DOdds ratioBE riskEsophagusAbstractTextL increaseSingle nucleotide polymorphismsConflicting resultsAdenocarcinomaPatientsSNP associationsRisk
2018
Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus
Dong J, Levine DM, Buas MF, Zhang R, Onstad L, Fitzgerald RC, Consortium S, Corley DA, Shaheen NJ, Lagergren J, Hardie LJ, Reid BJ, Iyer PG, Risch HA, Caldas C, Caldas I, Pharoah PD, Liu G, Gammon MD, Chow WH, Bernstein L, Bird NC, Ye W, Wu AH, Anderson LA, MacGregor S, Whiteman DC, Vaughan TL, Thrift AP. Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus. Clinical Gastroenterology And Hepatology 2018, 16: 1598-1606.e4. PMID: 29551738, PMCID: PMC6162842, DOI: 10.1016/j.cgh.2018.03.007.Peer-Reviewed Original ResearchConceptsRisk of EACGastroesophageal reflux diseaseBarrett's esophagusEsophageal adenocarcinomaGERD symptomsWide association studySmoking statusSymptoms of GERDChromosome 1p34.3Environmental factorsChromosome 2p25.1Association of BMIChromosome 1Borderline significant interactionAssociation studiesGene studiesOesophageal cancer studiesSusceptibility lociCase-control logistic regressionGenesChromosome 15q14Genetic variantsReflux diseaseSmoking historyBMI measurements
2017
Determining Risk of Barrett’s Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants
Dong J, Buas MF, Gharahkhani P, Kendall BJ, Onstad L, Zhao S, Anderson LA, Wu AH, Ye W, Bird NC, Bernstein L, Chow WH, Gammon MD, Liu G, Caldas C, Pharoah PD, Risch HA, Iyer PG, Reid BJ, Hardie LJ, Lagergren J, Shaheen NJ, Corley DA, Fitzgerald RC, consortium S, Whiteman DC, Vaughan TL, Thrift AP. Determining Risk of Barrett’s Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants. Gastroenterology 2017, 154: 1273-1281.e3. PMID: 29247777, PMCID: PMC5880715, DOI: 10.1053/j.gastro.2017.12.003.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaArea Under CurveAustraliaBarrett EsophagusCase-Control StudiesDatabases, FactualDecision Support TechniquesEsophageal NeoplasmsEuropeFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLife StyleLogistic ModelsMaleMiddle AgedModels, GeneticMolecular EpidemiologyMultifactorial InheritanceNorth AmericaOdds RatioPhenotypePolymorphism, Single NucleotidePredictive Value of TestsRisk AssessmentRisk FactorsROC CurveConceptsGastroesophageal reflux diseaseBarrett's esophagusEsophageal adenocarcinomaLifestyle factorsPolygenic risk scoresGERD symptomsNon-genetic factorsDemographic/lifestyle factorsNet reclassification improvementCharacteristic curve analysisAUC valuesRisk prediction modelEsophageal cancer studyInternational Barrett'sReflux diseaseHighest quartileNet reclassificationEpidemiologic factorsReclassification improvementLowest quartileHigh riskRisk scorePatientsEsophagusAbstractText
2016
Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis
Gharahkhani P, Fitzgerald RC, Vaughan TL, Palles C, Gockel I, Tomlinson I, Buas MF, May A, Gerges C, Anders M, Becker J, Kreuser N, Noder T, Venerito M, Veits L, Schmidt T, Manner H, Schmidt C, Hess T, Böhmer AC, Izbicki JR, Hölscher AH, Lang H, Lorenz D, Schumacher B, Hackelsberger A, Mayershofer R, Pech O, Vashist Y, Ott K, Vieth M, Weismüller J, Nöthen MM, Consortium B, Consortium E, Consortium W, Attwood S, Barr H, Chegwidden L, de Caestecker J, Harrison R, Love SB, MacDonald D, Moayyedi P, Prenen H, Watson RGP, Iyer PG, Anderson LA, Bernstein L, Chow WH, Hardie LJ, Lagergren J, Liu G, Risch HA, Wu AH, Ye W, Bird NC, Shaheen NJ, Gammon MD, Corley DA, Caldas C, Moebus S, Knapp M, Peters WHM, Neuhaus H, Rösch T, Ell C, MacGregor S, Pharoah P, Whiteman DC, Jankowski J, Schumacher J. Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis. The Lancet Oncology 2016, 17: 1363-1373. PMID: 27527254, PMCID: PMC5052458, DOI: 10.1016/s1470-2045(16)30240-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBarrett EsophagusEsophageal NeoplasmsGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRiskConceptsGenome-wide association studiesNew risk lociRisk lociAssociation studiesGenome-wide significant lociNovel genetic risk variantsHigh-density single nucleotide polymorphism arraysGenome-wide significance thresholdFunctional annotation databasesMuscle cell differentiationPathway-based methodsWide association studyNovel risk lociEsophagus developmentSingle nucleotide polymorphism arrayNovel genetic markersNucleotide polymorphism arrayRelevant cellular mechanismsAnnotation enrichmentGenetic risk variantsMesenchyme developmentSignificant lociAnnotation databasesNorth AmericaGenetic markersGermline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma
Buas MF, He Q, Johnson LG, Onstad L, Levine DM, Thrift AP, Gharahkhani P, Palles C, Lagergren J, Fitzgerald RC, Ye W, Caldas C, Bird NC, Shaheen NJ, Bernstein L, Gammon MD, Wu AH, Hardie LJ, Pharoah PD, Liu G, Iyer P, Corley DA, Risch HA, Chow WH, Prenen H, Chegwidden L, Love S, Attwood S, Moayyedi P, MacDonald D, Harrison R, Watson P, Barr H, deCaestecker J, Tomlinson I, Jankowski J, Whiteman DC, MacGregor S, Vaughan TL, Madeleine MM. Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma. Gut 2016, 66: 1739. PMID: 27486097, PMCID: PMC5296402, DOI: 10.1136/gutjnl-2016-311622.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBarrett EsophagusCytokinesEsophageal NeoplasmsFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyGerm-Line MutationGlutathione TransferaseHLA AntigensHumansInflammationMaleMiddle AgedNF-kappa BOxidative StressPolymorphism, Single NucleotidePrincipal Component AnalysisProstaglandin-Endoperoxide SynthasesRisk FactorsSignal TransductionConceptsBarrett's esophagusBE casesSingle nucleotide polymorphismsGermline variationOesophageal adenocarcinoma incidenceHuman leucocyte antigenInflammation-related pathwaysSymptomatic refluxSystemic inflammationAdenocarcinoma incidenceOesophageal adenocarcinomaOA pathogenesisInflammatory processLeucocyte antigenOA casesRisk factorsCOX pathwayBE riskOA riskDisease riskEsophagusStrong expression quantitative trait locusGenetic susceptibilityNuclear factorExpression quantitative trait lociConstrained Score Statistics Identify Genetic Variants Interacting with Multiple Risk Factors in Barrett’s Esophagus
Dai JY, de Dieu Tapsoba J, Buas MF, Consortium T, Chow W, Shaheen N, Anderson L, Corley D, Gammon M, Hardie L, Lagergren J, Whiteman D, Risch H, Vaughan T. Constrained Score Statistics Identify Genetic Variants Interacting with Multiple Risk Factors in Barrett’s Esophagus. American Journal Of Human Genetics 2016, 99: 352-365. PMID: 27486777, PMCID: PMC4974090, DOI: 10.1016/j.ajhg.2016.06.018.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAge FactorsBarrett EsophagusEsophageal NeoplasmsFemaleGastroesophageal RefluxGene-Environment InteractionGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansMaleModels, GeneticObesityOdds RatioPolymorphism, Single NucleotideReproducibility of ResultsRisk FactorsSample SizeSex FactorsSmokingConceptsBarrett's esophagusEsophageal adenocarcinomaGene-environment interactionsMultiple risk factorsEsophageal Adenocarcinoma ConsortiumEnvironmental exposure dataGenetic variantsGastresophageal refluxTobacco smokingRisk factorsCancer epidemiologyEsophagusExposure dataAdenocarcinomaMultivariate gene-environment interactionsLow statistical powerTesting strategiesGenome-wide significanceSmokingObesityStatistical powerEpidemiologyReflux
2015
Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk
Lee E, Stram DO, Ek WE, Onstad LE, MacGregor S, Gharahkhani P, Ye W, Lagergren J, Shaheen NJ, Murray LJ, Hardie LJ, Gammon MD, Chow WH, Risch HA, Corley DA, Levine DM, Whiteman DC, Bernstein L, Bird NC, Vaughan TL, Wu AH. Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk. Cancer Epidemiology Biomarkers & Prevention 2015, 24: 1801-1803. PMID: 26364162, PMCID: PMC4648999, DOI: 10.1158/1055-9965.epi-15-0596.Peer-Reviewed Original ResearchConceptsRisk of EACBody mass indexBarrett's esophagusEsophageal adenocarcinomaCommon cancerEffect modificationEsophageal adenocarcinoma riskMultiple cancer sitesRisk variantsGenome-wide association studiesGenetic susceptibility studiesCase patientsAdenocarcinoma riskMass indexCancer sitesGenetic risk variantsEsophagusPleiotropic genetic associationsControl participantsCancerHeartburnRiskMultiple testingGenetic associationCancer risk lociA Newly Identified Susceptibility Locus near FOXP1 Modifies the Association of Gastroesophageal Reflux with Barrett's Esophagus
Dai JY, de Dieu Tapsoba J, Buas MF, Onstad LE, Levine DM, Risch HA, Chow WH, Bernstein L, Ye W, Lagergren J, Bird NC, Corley DA, Shaheen NJ, Wu AH, Reid BJ, Hardie LJ, Whiteman DC, Vaughan TL. A Newly Identified Susceptibility Locus near FOXP1 Modifies the Association of Gastroesophageal Reflux with Barrett's Esophagus. Cancer Epidemiology Biomarkers & Prevention 2015, 24: 1739-1747. PMID: 26377193, PMCID: PMC4816532, DOI: 10.1158/1055-9965.epi-15-0507.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBarrett EsophagusCase-Control StudiesEsophageal NeoplasmsFemaleForkhead Transcription FactorsGastroesophageal RefluxGenetic LociGenetic MarkersGenetic Predisposition to DiseaseGenome-Wide Association StudyHomozygoteHumansMalePolymorphism, Single NucleotideRepressor ProteinsRisk FactorsConceptsBody mass indexBarrett's esophagusEsophageal adenocarcinomaWeekly heartburnCase patientsSmoking statusMass indexRisk factorsSingle nucleotide polymorphismsMinor alleleBarrett's esophagus riskGene-exposure interactionsLeast weekly heartburnGastroesophageal reflux diseaseImportant risk factorGermline single nucleotide polymorphismsLogistic regression modelsExposure-disease associationsReflux symptomsGastroesophageal refluxReflux diseaseCigarette smokingSusceptibility single nucleotide polymorphismsOdds ratioEsophagusPolymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma
Ek WE, Lagergren K, Cook M, Wu AH, Abnet CC, Levine D, Chow W, Bernstein L, Risch HA, Shaheen NJ, Bird NC, Corley DA, Hardie LJ, Fitzgerald RC, Gammon MD, Romero Y, Liu G, Ye W, Vaughan TL, MacGregor S, Whiteman DC, Westberg L, Lagergren J. Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma. International Journal Of Cancer 2015, 138: 1146-1152. PMID: 26414697, PMCID: PMC4715576, DOI: 10.1002/ijc.29863.Peer-Reviewed Original ResearchConceptsRisk of BEBarrett's esophagusEsophageal adenocarcinomaSingle nucleotide polymorphismsAndrogen pathwayRisk of EACStrong male predominanceBody mass indexMale predominanceTobacco smokingTobacco smokersBE patientsHip ratioEAC patientsSex hormonesReflux statusLarger sample sizeEsophagusInfluence riskGenetic epidemiological analysisPatientsControl participantsAdenocarcinomaRiskGenetic variantsPolymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett’s Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium
Lagergren K, Ek WE, Levine D, Chow WH, Bernstein L, Casson AG, Risch HA, Shaheen NJ, Bird NC, Reid BJ, Corley DA, Hardie LJ, Wu AH, Fitzgerald RC, Pharoah P, Caldas C, Romero Y, Vaughan TL, MacGregor S, Whiteman D, Westberg L, Nyren O, Lagergren J. Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett’s Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium. PLOS ONE 2015, 10: e0138738. PMID: 26406593, PMCID: PMC4583498, DOI: 10.1371/journal.pone.0138738.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaADP-ribosyl Cyclase 1AromataseBarrett EsophagusEsophageal NeoplasmsEstrogen Receptor alphaEstrogen Receptor betaFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMaleMembrane GlycoproteinsOxytocinPolymorphism, Single NucleotideReceptors, OxytocinSex FactorsConceptsKey genesGenetic variantsGenes of relevanceGene-based approachesAssociation studiesGenesOxytocin pathwaysGenetic epidemiological studiesEstrogen receptor alphaRisk of OACRisk of BEPathwayReceptor alphaOesophageal adenocarcinomaBarrett's esophagusNorth AmericaReplicationPolymorphismEstrogen pathwayVariantsStrong male predominanceOAC patientsMalesBO patientsMale predominanceAge‐specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium
Drahos J, Xiao Q, Risch HA, Freedman ND, Abnet CC, Anderson LA, Bernstein L, Brown L, Chow W, Gammon MD, Kamangar F, Liao LM, Murray LJ, Ward MH, Ye W, Wu AH, Vaughan TL, Whiteman DC, Cook MB. Age‐specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium. International Journal Of Cancer 2015, 138: 55-64. PMID: 26175109, PMCID: PMC4607633, DOI: 10.1002/ijc.29688.Peer-Reviewed Original ResearchConceptsBody mass indexNonsteroidal anti-inflammatory drugsRecurrent gastroesophageal refluxGastroesophageal refluxOlder age groupsAge groupsOdds ratioInternational BEACON ConsortiumRisk factor profileMultivariable logistic regressionEsophagogastric junction adenocarcinomaConfidence intervalsCase-control studyAge-specific associationsAge-specific riskAnti-inflammatory drugsEsophageal Adenocarcinoma ConsortiumIndividual participant dataInternational Barrett'sNSAID useJunction adenocarcinomaMass indexSmoking statusCigarette smokingEA patientsDietary flavonoid intake and Barrett's esophagus in western Washington State
Petrick JL, Steck SE, Bradshaw PT, Chow WH, Engel LS, He K, Risch HA, Vaughan TL, Gammon MD. Dietary flavonoid intake and Barrett's esophagus in western Washington State. Annals Of Epidemiology 2015, 25: 730-735.e2. PMID: 26169148, PMCID: PMC4567908, DOI: 10.1016/j.annepidem.2015.05.010.Peer-Reviewed Original ResearchConceptsOdds of BESpecialized intestinal metaplasiaBarrett's esophagusOdds ratioIntestinal metaplasiaInverse associationPrecursor lesionsWestern Washington StateDietary flavonoid intakeDecreased odds ratioFood frequency questionnaireAdequate dietary intakeBody mass indexCase-control investigationCancer precursor lesionsCase-control study participantsDietary sourcesLogistic regression modelsFlavonoid classesMain dietary sourceAnthocyanidin intakeFrequency questionnaireFlavonoid intakeMass indexIsoflavone intakeMiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium
Buas MF, Onstad L, Levine DM, Risch HA, Chow WH, Liu G, Fitzgerald RC, Bernstein L, Ye W, Bird NC, Romero Y, Casson AG, Corley DA, Shaheen NJ, Wu AH, Gammon MD, Reid BJ, Hardie LJ, Peters U, Whiteman DC, Vaughan TL. MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium. PLOS ONE 2015, 10: e0128617. PMID: 26039359, PMCID: PMC4454432, DOI: 10.1371/journal.pone.0128617.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBarrett EsophagusCase-Control StudiesEsophageal NeoplasmsEsophagusFemaleGastroesophageal RefluxGene Expression RegulationGenetic LociGenome-Wide Association StudyHumansMaleMicroRNAsMiddle AgedObesityPolymorphism, Single NucleotideRisk FactorsSex FactorsSmokingWhite PeopleConceptsGenome-wide association studiesSingle nucleotide polymorphismsPost-transcriptional gene regulationGenome-wide association analysisMiRNA-related single nucleotide polymorphismsMiRNA gene lociSmall non-coding RNAsClasses of genesMiRNA-targeted mRNAsMiRNA biogenesis genesGenetic variantsNon-coding RNAsCommon genetic variantsGermline genetic variantsMiRNA genesBiogenesis genesGene regulationCore pathwaysGene locusAssociation studiesAssociation analysisGenesNucleotide polymorphismsNominal associationEuropean ancestry
2014
Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus
Palles C, Chegwidden L, Li X, Findlay JM, Farnham G, Giner F, Peppelenbosch MP, Kovac M, Adams CL, Prenen H, Briggs S, Harrison R, Sanders S, MacDonald D, Haigh C, Tucker A, Love S, Nanji M, deCaestecker J, Ferry D, Rathbone B, Hapeshi J, Barr H, Moayyedi P, Watson P, Zietek B, Maroo N, Gay L, Underwood T, Boulter L, McMurtry H, Monk D, Patel P, Ragunath K, Al Dulaimi D, Murray I, Koss K, Veitch A, Trudgill N, Nwokolo C, Rembacken B, Atherfold P, Green E, Ang Y, Kuipers EJ, Chow W, Paterson S, Kadri S, Beales I, Grimley C, Mullins P, Beckett C, Farrant M, Dixon A, Kelly S, Johnson M, Wajed S, Dhar A, Sawyer E, Roylance R, Onstad L, Gammon MD, Corley DA, Shaheen NJ, Bird NC, Hardie LJ, Reid BJ, Ye W, Liu G, Romero Y, Bernstein L, Wu AH, Casson AG, Fitzgerald R, Whiteman DC, Risch HA, Levine DM, Vaughan TL, Verhaar AP, van den Brande J, Toxopeus EL, Spaander MC, Wijnhoven BP, van der Laan LJ, Krishnadath K, Wijmenga C, Trynka G, McManus R, Reynolds JV, O’Sullivan J, MacMathuna P, McGarrigle SA, Kelleher D, Vermeire S, Cleynen I, Bisschops R, Tomlinson I, Jankowski J. Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus. Gastroenterology 2014, 148: 367-378. PMID: 25447851, PMCID: PMC4315134, DOI: 10.1053/j.gastro.2014.10.041.Peer-Reviewed Original ResearchConceptsProtein-coding genesSingle nucleotide polymorphismsTranscription factorsBone morphogenetic protein (BMP) pathwayWide association studyFurther single nucleotide polymorphismsRisk single nucleotide polymorphismsEsophageal developmentCardiac developmentRisk lociAssociation studiesFurther lociProtein pathwayChromosome 6p21GenesNucleotide polymorphismsLociTbx5GDF7Promising variantsPolymorphismBarx1FOXF1KbCRTC1Integrative post-genome-wide association analysis of CDKN2A and TP53 SNPs and risk of esophageal adenocarcinoma
Buas MF, Levine DM, Makar KW, Utsugi H, Onstad L, Li X, Galipeau PC, Shaheen NJ, Hardie LJ, Romero Y, Bernstein L, Gammon MD, Casson AG, Bird NC, Risch HA, Ye W, Liu G, Corley DA, Blount PL, Fitzgerald RC, Whiteman DC, Wu AH, Reid BJ, Vaughan TL. Integrative post-genome-wide association analysis of CDKN2A and TP53 SNPs and risk of esophageal adenocarcinoma. Carcinogenesis 2014, 35: 2740-2747. PMID: 25280564, PMCID: PMC4247522, DOI: 10.1093/carcin/bgu207.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedBarrett EsophagusCase-Control StudiesCyclin-Dependent Kinase Inhibitor p16Disease ProgressionEsophageal NeoplasmsFemaleFollow-Up StudiesGenome-Wide Association StudyHumansMaleMiddle AgedNeoplasm StagingPolymorphism, Single NucleotidePrognosisRisk FactorsTumor Suppressor Protein p53ConceptsEsophageal adenocarcinomaBarrett's esophagusSingle nucleotide polymorphismsRisk of EACPredictors of progressionGermline single nucleotide polymorphismsTP53 single nucleotide polymorphismsNucleotide polymorphismsCDKN2A polymorphismsEA tumorsFrequent somatic mutationsProspective cohortCDKN2A variantsMale genderRisk factorsReduced riskTumor suppressor gene CDKN2ACaucasian raceMiR-663bEA casesSomatic alterationsGermline variationAdenocarcinomaGenes CDKN2AEsophagusObesity and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: A Mendelian Randomization Study
Thrift AP, Shaheen NJ, Gammon MD, Bernstein L, Reid BJ, Onstad L, Risch HA, Liu G, Bird NC, Wu AH, Corley DA, Romero Y, Chanock SJ, Chow WH, Casson AG, Levine DM, Zhang R, Ek WE, MacGregor S, Ye W, Hardie LJ, Vaughan TL, Whiteman DC. Obesity and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: A Mendelian Randomization Study. Journal Of The National Cancer Institute 2014, 106: dju252. PMID: 25269698, PMCID: PMC4200028, DOI: 10.1093/jnci/dju252.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedBarrett EsophagusBody Mass IndexEsophageal NeoplasmsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisMiddle AgedObesityPolymorphism, Single NucleotidePrecancerous ConditionsPredictive Value of TestsRisk AssessmentRisk FactorsConceptsBody mass indexBarrett's esophagusEsophageal adenocarcinomaGenetic risk scoreConventional epidemiologic analysisRisk scoreEpidemiologic analysisRisk of EACLifetime body mass indexInstrumental variable analysisGastroesophageal reflux symptomsMendelian randomization studyMendelian randomization approachGenetic susceptibility studiesGenetic propensityReflux symptomsMass indexEAC riskPotential confoundersEsophageal metaplasiaObservational studyHigh riskObesityUnconfounded effectRandomization studyRisk of Esophageal Adenocarcinoma Decreases With Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization
Thrift AP, Risch HA, Onstad L, Shaheen NJ, Casson AG, Bernstein L, Corley DA, Levine DM, Chow W, Reid BJ, Romero Y, Hardie LJ, Liu G, Wu AH, Bird NC, Gammon MD, Ye W, Whiteman DC, Vaughan TL. Risk of Esophageal Adenocarcinoma Decreases With Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization. Clinical Gastroenterology And Hepatology 2014, 12: 1667-1676.e1. PMID: 24530603, PMCID: PMC4130803, DOI: 10.1016/j.cgh.2014.01.039.Peer-Reviewed Original ResearchConceptsRisk of EACBarrett's esophagusEsophageal adenocarcinomaMendelian randomization analysisOdds ratioCases of BEGastroesophageal reflux symptomsStrata of ageRandomization analysisBody mass indexMultivariable logistic regressionClinical risk stratificationEsophageal Adenocarcinoma ConsortiumMendelian randomization studyGenetic risk scoreConventional epidemiologic analysisReflux symptomsRisk stratificationMass indexInverse associationRisk scoreUnconfounded effectRandomization studyAbstractTextEpidemiologic analysis
2013
Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux
Ek WE, Levine DM, D’Amato M, Pedersen NL, Magnusson PK, Bresso F, Onstad LE, Schmidt PT, Törnblom H, Nordenstedt H, Romero Y, , Chow W, Murray L, Gammon M, Liu G, Bernstein L, Casson A, Risch H, Shaheen N, Bird N, Reid B, Corley D, Hardie L, Ye W, Wu A, Zucchelli M, Spector T, Hysi P, Vaughan T, Whiteman D, MacGregor S. Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux. Journal Of The National Cancer Institute 2013, 105: 1711-1718. PMID: 24168968, PMCID: PMC3833931, DOI: 10.1093/jnci/djt303.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedBarrett EsophagusCase-Control StudiesChromosome DisordersEsophageal NeoplasmsFemaleGastroesophageal RefluxGenome-Wide Association StudyGerm-Line MutationHumansMaleMiddle AgedPolymorphism, Single NucleotidePredictive Value of TestsPrevalenceRisk AssessmentRisk FactorsSex FactorsSoftwareTwin Studies as Topic