2024
Understanding risk factors for endometrial cancer in young women
Peeri N, Bertrand K, Na R, De Vivo I, Setiawan V, Seshan V, Alemany L, Chen Y, Clarke M, Clendenen T, Cook L, Costas L, Dal Maso L, Freudenheim J, Friedenreich C, Gierach G, Goodman M, La Vecchia C, Levi F, Lopez-Querol M, Lu L, Moysich K, Mutter G, Naduparambil J, Negri E, O’Connell K, O’Mara T, Palmer J, Parazzini F, Penney K, Petruzella S, Reynolds P, Ricceri F, Risch H, Rohan T, Sacerdote C, Sandin S, Shu X, Stolzenberg-Solomon R, Webb P, Wentzensen N, Wilkens L, Xu W, Yu H, Zeleniuch-Jacquotte A, Zheng W, Guo X, Lipworth L, Du M. Understanding risk factors for endometrial cancer in young women. Journal Of The National Cancer Institute 2024, djae210. PMID: 39235934, DOI: 10.1093/jnci/djae210.Peer-Reviewed Original ResearchRisk factorsEpidemiology of Endometrial Cancer ConsortiumEC riskOdds ratioOlder womenAverage risk womenKnowledge of risk factorsConfidence intervalsPopulation attributable fractionEstimate odds ratiosInverse association with ageYoung womenAmerican Cancer SocietyAssociated with reduced riskIncreased riskEndometrial cancerUnderstanding risk factorsEC risk factorsOral contraceptive useAttributable fractionRisk womenCurrent smokingCancer ConsortiumCancer SocietyAssociated with ageDetection of hepatocellular carcinoma methylation markers in salivary DNA
Mezzacappa C, Wang Z, Lu L, Risch H, Taddei T, Yu H. Detection of hepatocellular carcinoma methylation markers in salivary DNA. Bioscience Reports 2024, 44: bsr20232063. PMID: 38457142, PMCID: PMC10958141, DOI: 10.1042/bsr20232063.Peer-Reviewed Original ResearchHepatocellular carcinoma screeningCase patientsHepatocellular carcinomaControl subjectsDiagnosis of hepatocellular carcinomaAssociated with hepatocellular carcinomaScreening testSalivary DNASaliva-based testCpG sitesStudy of risk factorsSalivary DNA methylationDNA methylationViral hepatitisCirculating DNAAlterations to DNA methylationRisk factorsMethylation markersPatientsRegulation of cell cycle progressionBlood samplesCell cycle progressionAffected individualsAlternative to blood samplingMultiple comparisons
2023
Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival
Wang Z, Katsaros D, Wang J, Biglio N, Hernandez B, Fei P, Lu L, Risch H, Yu H. Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival. Scientific Reports 2023, 13: 18962. PMID: 37923775, PMCID: PMC10624674, DOI: 10.1038/s41598-023-45932-4.Peer-Reviewed Original ResearchConceptsImmune cell clustersT cellsHost immunityImmune cellsUnsupervised hierarchical clusteringImmune responseCD8-positive T cellsMemory CD4 T cellsCox regression survival analysisRegulatory T cellsPositive T cellsCD4 T cellsDifferent immune cellsDistinct immune responsesBreast cancer survivalImmune cell subtypesMemory B cellsImmune cell typesRegression survival analysisCell clustersBreast cancer progressionT cell receptor signalingCytokine stormOverall survivalFavorable survivalNight shift work, sleep duration and endometrial cancer risk: A pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2)
Frias-Gomez J, Alemany L, Benavente Y, Clarke M, de Francisco J, De Vivo I, Du M, Goodman M, Lacey J, Liao L, Lipworth L, Lu L, Merritt M, Michels K, O'Connell K, Paytubi S, Pelegrina B, Peremiquel-Trillas P, Petruzella S, Ponce J, Risch H, Setiawan V, Schouten L, Shu X, Trabert B, Van den Brandt P, Wentzensen N, Wilkens L, Yu H, Costas L. Night shift work, sleep duration and endometrial cancer risk: A pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2). Sleep Medicine Reviews 2023, 72: 101848. PMID: 37716022, PMCID: PMC10840870, DOI: 10.1016/j.smrv.2023.101848.Peer-Reviewed Original ResearchConceptsNight shift workEndometrial Cancer ConsortiumEndometrial cancer riskEndometrial cancerSleep durationShift workPostmenopausal womenPooled analysisInverse associationOdds ratioCancer riskCancer ConsortiumNon-significant inverse associationStudy-specific odds ratiosEndometrial cancer casesStrong risk factorConfidence intervalsLong sleep durationDaily sleep durationObese womenRisk factorsCancer casesLogistic regressionIndividual dataCancerPlausibility, not science, has dominated public discussions of the COVID pandemic
Risch H. Plausibility, not science, has dominated public discussions of the COVID pandemic. American Journal Of Economics And Sociology 2023, 82: 411-424. DOI: 10.1111/ajes.12539.Peer-Reviewed Original ResearchRelationship between ABO Blood Group Alleles and Pancreatic Cancer Is Modulated by Secretor (FUT2) Genotype, but Not Lewis Antigen (FUT3) Genotype.
Kim J, Yuan C, Amundadottir L, Wolpin B, Klein A, Risch H, Kraft P. Relationship between ABO Blood Group Alleles and Pancreatic Cancer Is Modulated by Secretor (FUT2) Genotype, but Not Lewis Antigen (FUT3) Genotype. Cancer Epidemiology Biomarkers & Prevention 2023, 32: 1242-1248. PMID: 37342060, PMCID: PMC10527950, DOI: 10.1158/1055-9965.epi-23-0009.Peer-Reviewed Original ResearchConceptsNon-O blood typeABO blood groupSecretor statusBlood typeBlood groupNon-O blood groupMultivariable logistic regressionConfidence intervalsPancreatic cancer riskO blood typeABO blood typeABO blood group allelesPancreatic ductal adenocarcinoma (PDAC) riskAdenocarcinoma riskAntigen genotypesPancreatic cancerEffect modificationSecretor genotypesCancer riskPDAC riskCancer ConsortiumBlood group allelesLogistic regressionLewis antigensWestern populationsFolate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case–Control Study from the Ovarian Cancer Association Consortium
Gersekowski K, Ibiebele T, Group F, Doherty J, Harris H, Goodman M, Terry K, Wu A, Bandera E, Qin B, Ong J, Tyrer J, Dixon-Suen S, Modugno F, Risch H, Webb P. Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case–Control Study from the Ovarian Cancer Association Consortium. Cancer Epidemiology Biomarkers & Prevention 2023, 32: of1-of10. PMID: 37220873, PMCID: PMC10390886, DOI: 10.1158/1055-9965.epi-23-0121.Peer-Reviewed Original ResearchConceptsOvarian cancer riskHigh dietary folate intakeDietary folate intakeCase-control studyFolate intakeOvarian cancerOvarian Cancer Association ConsortiumCancer riskOdds ratioMendelian randomizationSelf-reported endometriosisSupplemental folate intakeHigh folate intakeHigh folate dietCancer-promoting effectsPooled analysisFolate dietPrecancerous lesionsFolate statusEndometriosisIncrease riskCancerCancer typesLogistic regressionIntakeDynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma
Lu L, Risch E, Halaban R, Zhen P, Bacchiocchi A, Risch H. Dynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma. International Immunopharmacology 2023, 118: 110092. PMID: 37004344, DOI: 10.1016/j.intimp.2023.110092.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeSoluble PD-L1 (sPD-L1) levelsPD-L1 ratioPD-L1 levelsSoluble PD-1Soluble PD-L1PD-L1PD-1Patient survivalSurvival statusPD-1/PD-L1Immune checkpoints PD-1T cell exhaustionPatients' survival statusSolid tumor typesInitial immunotherapyCheckpoint blockadeMelanoma patientsPoor prognosisRetrospective studyPatient responseCell exhaustionTumor typesMelanomaSurvivalGenome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions
Lindström S, Wang L, Feng H, Majumdar A, Huo S, Macdonald J, Harrison T, Turman C, Chen H, Mancuso N, Bammler T, Consortium B, Gallinger S, Gruber S, Gunter M, Le Marchand L, Moreno V, Offit K, Study G, De Vivo I, O’Mara T, Spurdle A, Tomlinson I, Consortium E, Fitzgerald R, Gharahkhani P, Gockel I, Jankowski J, Macgregor S, Schumacher J, Barnholtz-Sloan J, Bondy M, Houlston R, Jenkins R, Melin B, Wrensch M, Brennan P, Christiani D, Johansson M, Mckay J, Aldrich M, Amos C, Landi M, Tardon A, Consortium I, Bishop D, Demenais F, Goldstein A, Iles M, Kanetsky P, Law M, Consortium O, Amundadottir L, Stolzenberg-Solomon R, Wolpin B, Consortium P, Klein A, Petersen G, Risch H, Consortium T, Chanock S, Purdue M, Scelo G, Pharoah P, Kar S, Hung R, Pasaniuc B, Kraft P. Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions. Journal Of The National Cancer Institute 2023, 115: 712-732. PMID: 36929942, PMCID: PMC10248849, DOI: 10.1093/jnci/djad043.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscriptome-wide association studyCancer susceptibility lociGenome-wide genetic correlationSusceptibility lociAssociation studiesMultiple cancer typesCancer genome-wide association studyGenome-wide analysisCross-disease analysisGenetic correlationsSusceptibility regionsGWAS summary statisticsCancer typesGenetic risk variantsDistinct lociCancer heritabilityLociRisk variantsGenetic contributionEuropean ancestryPleiotropyAdditional regionsDifferent cancersHeritabilityRisk prediction models for endometrial cancer: development and validation in an international consortium
Shi J, Kraft P, Rosner B, Benavente Y, Black A, Brinton L, Chen C, Clarke M, Cook L, Costas L, Dal Maso L, Freudenheim J, Frias-Gomez J, Friedenreich C, Garcia-Closas M, Goodman M, Johnson L, La Vecchia C, Levi F, Lissowska J, Lu L, McCann S, Moysich K, Negri E, O'Connell K, Parazzini F, Petruzella S, Polesel J, Ponte J, Rebbeck T, Reynolds P, Ricceri F, Risch H, Sacerdote C, Setiawan V, Shu X, Spurdle A, Trabert B, Webb P, Wentzensen N, Wilkens L, Xu W, Yang H, Yu H, Du M, De Vivo I. Risk prediction models for endometrial cancer: development and validation in an international consortium. Journal Of The National Cancer Institute 2023, 115: 552-559. PMID: 36688725, PMCID: PMC10165481, DOI: 10.1093/jnci/djad014.Peer-Reviewed Original ResearchConceptsNurses' Health StudyRisk prediction modelNHS IIEndometrial cancerHealth StudyGenetic factorsEndometrial cancer incidence ratesOvarian Cancer Screening TrialCancer risk prediction modelsEndometrial Cancer ConsortiumPostmenopausal white womenCancer Screening TrialCancer risk stratificationCase-control studyRisk factor distributionCancer incidence ratesRelative risk estimatesEpidemiologic modelHeterogeneous study populationsPublic health practiceProphylactic hysterectomyRisk stratificationEpidemiologic factorsIncidence rateSelect cohortLifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis
Fu Z, Brooks M, Irvin S, Jordan S, Aben K, Anton-Culver H, Bandera E, Beckmann M, Berchuck A, Brooks-Wilson A, Chang-Claude J, Cook L, Cramer D, Cushing-Haugen K, Doherty J, Ekici A, Fasching P, Fortner R, Gayther S, Gentry-Maharaj A, Giles G, Goode E, Goodman M, Group A, Harris H, Hein A, Kaaks R, Kiemeney L, Köbel M, Kotsopoulos J, Kotsopoulos J, Le N, Lee A, Matsuo K, McGuire V, McLaughlin J, Menon U, Milne R, Moysich K, Pearce C, Pike M, Qin B, Ramus S, Riggan M, Rothstein J, Schildkraut J, Sieh W, Sutphen R, Terry K, Thompson P, Titus L, van Altena A, White E, Whittemore A, Wu A, Zheng W, Ziogas A, Taylor S, Tang L, Songer T, Wentzensen N, Webb P, Risch H, Modugno F. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis. Journal Of The National Cancer Institute 2023, 115: 539-551. PMID: 36688720, PMCID: PMC10165492, DOI: 10.1093/jnci/djad011.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerOral contraceptive useClear cell histotypeOvulatory yearsOvulation suppressionOdds ratioOvarian cancerContraceptive useNonmucinous epithelial ovarian cancerConfidence intervalsConsistent protective effectCase patientsMucinous tumorsPooled analysisProtective effectEOC riskControl participantsHistotypeCancerOvulationAssociationRegression modelsRiskYearsBeta coefficients
2022
Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis
Brasky T, Hade E, Cohn D, Newton A, Petruzella S, O'Connell K, Bertrand K, Cook L, De Vivo I, Du M, Freudenheim J, Friedenreich C, Goodman M, Gorzelitz J, Ibiebele T, Krogh V, Liao L, Lipworth L, Lu L, McCann S, O'Mara T, Palmer J, Ponte J, Prizment A, Risch H, Sandin S, Schouten L, Setiawan V, Shu X, Trabert B, van den Brandt P, Webb P, Wentzensen N, Wilkens L, Wolk A, Yu H, Neuhouser M. Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis. Gynecologic Oncology 2022, 169: 137-146. PMID: 36934308, PMCID: PMC10025515, DOI: 10.1016/j.ygyno.2022.10.015.Peer-Reviewed Original ResearchConceptsEndometrial cancer riskEndometrial Cancer ConsortiumHigh dietary intakeCancer riskDietary intakeObese womenOdds ratioCancer ConsortiumDietary omega-3 fatty acidsOmega-3 fatty acidsEnergy-adjusted quartilesEndometrial cancer casesEndometrial cancer incidenceProspective cohort studyFood frequency questionnaireNormal-weight womenFatty acid intakeAdjusted odds ratioBody mass indexLong-chain omega-3Anti-inflammatory propertiesSubgroup of womenConfidence intervalsCase-control studyTwo-stage individual participant dataThe age-dependent association of risk factors with pancreatic cancer
Yuan C, Kim J, Wang QL, Lee AA, Babic A, Consortium P, Amundadottir LT, Ardanaz E, Arslan A, Beane-Freeman L, Bracci P, Bueno-de-Mesquita B, Du M, Gallinger S, Giles G, Goodman P, Katzke V, Klein A, Kooperberg C, Kraft P, Li D, Malats N, Marchand L, McCullough M, Milne R, Neoptolemos J, Perdomo S, Petersen G, Risch H, Shu X, Stolzenberg-Solomon R, Van Den Eeden S, Visvanathan K, White E, Wolpin B, Zheng W, Amundadottir L, Klein A, Li D, McCullough M, Petersen G, Risch H, Stolzenberg-Solomon R, Perez K, Ng K, Giovannucci E, Stampfer M, Kraft P, Wolpin B. The age-dependent association of risk factors with pancreatic cancer. Annals Of Oncology 2022, 33: 693-701. PMID: 35398288, PMCID: PMC9233063, DOI: 10.1016/j.annonc.2022.03.276.Peer-Reviewed Original ResearchConceptsPancreatic cancer casesRisk factorsPancreatic cancerProspective cohortMale sexBlack raceSEER programCancer casesPolygenic risk scoresRisk scoreProspective US cohort studyNon-modifiable risk factorsNon-O blood groupIncident pancreatic cancerUS cohort studyEnd Results ProgramPancreatic cancer riskAge-specific associationsEarly detection strategiesAge-dependent associationGenome-wide association studiesAdvanced diseaseCancer presentsCohort studyUS SurveillanceCorrection: Polygenic risk modeling for prediction of epithelial ovarian cancer risk
Dareng EO, Tyrer JP, Barnes DR, Jones MR, Yang X, Aben KKH, Adank MA, Agata S, Andrulis IL, Anton-Culver H, Antonenkova NN, Aravantinos G, Arun BK, Augustinsson A, Balmaña J, Bandera EV, Barkardottir RB, Barrowdale D, Beckmann MW, Beeghly-Fadiel A, Benitez J, Bermisheva M, Bernardini MQ, Bjorge L, Black A, Bogdanova NV, Bonanni B, Borg A, Brenton JD, Budzilowska A, Butzow R, Buys SS, Cai H, Caligo MA, Campbell I, Cannioto R, Cassingham H, Chang-Claude J, Chanock SJ, Chen K, Chiew YE, Chung WK, Claes KBM, Colonna S, Cook L, Couch F, Daly M, Dao F, Davies E, de la Hoya M, de Putter R, Dennis J, DePersia A, Devilee P, Diez O, Ding Y, Doherty J, Domchek S, Dörk T, du Bois A, Dürst M, Eccles D, Eliassen H, Engel C, Evans G, Fasching P, Flanagan J, Fortner R, Machackova E, Friedman E, Ganz P, Garber J, Gensini F, Giles G, Glendon G, Godwin A, Goodman M, Greene M, Gronwald J, Hahnen E, Haiman C, Håkansson N, Hamann U, Hansen T, Harris H, Hartman M, Heitz F, Hildebrandt M, Høgdall E, Høgdall C, Hopper J, Huang R, Huff C, Hulick P, Huntsman D, Imyanitov E, Isaacs C, Jakubowska A, James P, Janavicius R, Jensen A, Johannsson O, John E, Jones M, Kang D, Karlan B, Karnezis A, Kelemen L, Khusnutdinova E, Kiemeney L, Kim B, Kjaer S, Komenaka I, Kupryjanczyk J, Kurian A, Kwong A, Lambrechts D, Larson M, Lazaro C, Le N, Leslie G, Lester J, Lesueur F, Levine D, Li L, Li J, Loud J, Lu K, Lubiński J, Mai P, Manoukian S, Marks J, Matsuno R, Matsuo K, May T, McGuffog L, McLaughlin J, McNeish I, Mebirouk N, Menon U, Miller A, Milne R, Minlikeeva A, Modugno F, Montagna M, Moysich K, Munro E, Nathanson K, Neuhausen S, Nevanlinna H, Yie J, Nielsen H, Nielsen F, Nikitina-Zake L, Odunsi K, Offit K, Olah E, Olbrecht S, Olopade O, Olson S, Olsson H, Osorio A, Papi L, Park S, Parsons M, Pathak H, Pedersen I, Peixoto A, Pejovic T, Perez-Segura P, Permuth J, Peshkin B, Peterlongo P, Piskorz A, Prokofyeva D, Radice P, Rantala J, Riggan M, Risch H, Rodriguez-Antona C, Ross E, Rossing M, Runnebaum I, Sandler D, Santamariña M, Soucy P, Schmutzler R, Setiawan V, Shan K, Sieh W, Simard J, Singer C, Sokolenko A, Song H, Southey M, Steed H, Stoppa-Lyonnet D, Sutphen R, Swerdlow A, Tan Y, Teixeira M, Teo S, Terry K, Terry M, Thomassen M, Thompson P, Thomsen L, Thull D, Tischkowitz M, Titus L, Toland A, Torres D, Trabert B, Travis R, Tung N, Tworoger S, Valen E, van Altena A, van der Hout A, Van Nieuwenhuysen E, van Rensburg E, Vega A, Edwards D, Vierkant R, Wang F, Wappenschmidt B, Webb P, Weinberg C, Weitzel J, Wentzensen N, White E, Whittemore A, Winham S, Wolk A, Woo Y, Wu A, Yan L, Yannoukakos D, Zavaglia K, Zheng W, Ziogas A, Zorn K, Kleibl Z, Easton D, Lawrenson K, DeFazio A, Sellers T, Ramus S, Pearce C, Monteiro A, Cunningham J, Goode E, Schildkraut J, Berchuck A, Chenevix-Trench G, Gayther S, Antoniou A, Pharoah P. Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk. European Journal Of Human Genetics 2022, 30: 630-631. PMID: 35314806, PMCID: PMC9090804, DOI: 10.1038/s41431-022-01085-y.Peer-Reviewed Original ResearchPolygenic risk modeling for prediction of epithelial ovarian cancer risk
Dareng EO, Tyrer JP, Barnes DR, Jones MR, Yang X, Aben KKH, Adank MA, Agata S, Andrulis IL, Anton-Culver H, Antonenkova NN, Aravantinos G, Arun BK, Augustinsson A, Balmaña J, Bandera EV, Barkardottir RB, Barrowdale D, Beckmann MW, Beeghly-Fadiel A, Benitez J, Bermisheva M, Bernardini MQ, Bjorge L, Black A, Bogdanova NV, Bonanni B, Borg A, Brenton JD, Budzilowska A, Butzow R, Buys SS, Cai H, Caligo MA, Campbell I, Cannioto R, Cassingham H, Chang-Claude J, Chanock SJ, Chen K, Chiew YE, Chung WK, Claes KBM, Colonna S, Cook L, Couch F, Daly M, Dao F, Davies E, de la Hoya M, de Putter R, Dennis J, DePersia A, Devilee P, Diez O, Ding Y, Doherty J, Domchek S, Dörk T, du Bois A, Dürst M, Eccles D, Eliassen H, Engel C, Evans G, Fasching P, Flanagan J, Fortner R, Machackova E, Friedman E, Ganz P, Garber J, Gensini F, Giles G, Glendon G, Godwin A, Goodman M, Greene M, Gronwald J, Hahnen E, Haiman C, Håkansson N, Hamann U, Hansen T, Harris H, Hartman M, Heitz F, Hildebrandt M, Høgdall E, Høgdall C, Hopper J, Huang R, Huff C, Hulick P, Huntsman D, Imyanitov E, Isaacs C, Jakubowska A, James P, Janavicius R, Jensen A, Johannsson O, John E, Jones M, Kang D, Karlan B, Karnezis A, Kelemen L, Khusnutdinova E, Kiemeney L, Kim B, Kjaer S, Komenaka I, Kupryjanczyk J, Kurian A, Kwong A, Lambrechts D, Larson M, Lazaro C, Le N, Leslie G, Lester J, Lesueur F, Levine D, Li L, Li J, Loud J, Lu K, Lubiński J, Mai P, Manoukian S, Marks J, Matsuno R, Matsuo K, May T, McGuffog L, McLaughlin J, McNeish I, Mebirouk N, Menon U, Miller A, Milne R, Minlikeeva A, Modugno F, Montagna M, Moysich K, Munro E, Nathanson K, Neuhausen S, Nevanlinna H, Yie J, Nielsen H, Nielsen F, Nikitina-Zake L, Odunsi K, Offit K, Olah E, Olbrecht S, Olopade O, Olson S, Olsson H, Osorio A, Papi L, Park S, Parsons M, Pathak H, Pedersen I, Peixoto A, Pejovic T, Perez-Segura P, Permuth J, Peshkin B, Peterlongo P, Piskorz A, Prokofyeva D, Radice P, Rantala J, Riggan M, Risch H, Rodriguez-Antona C, Ross E, Rossing M, Runnebaum I, Sandler D, Santamariña M, Soucy P, Schmutzler R, Setiawan V, Shan K, Sieh W, Simard J, Singer C, Sokolenko A, Song H, Southey M, Steed H, Stoppa-Lyonnet D, Sutphen R, Swerdlow A, Tan Y, Teixeira M, Teo S, Terry K, Terry M, Thomassen M, Thompson P, Thomsen L, Thull D, Tischkowitz M, Titus L, Toland A, Torres D, Trabert B, Travis R, Tung N, Tworoger S, Valen E, van Altena A, van der Hout A, Van Nieuwenhuysen E, van Rensburg E, Vega A, Edwards D, Vierkant R, Wang F, Wappenschmidt B, Webb P, Weinberg C, Weitzel J, Wentzensen N, White E, Whittemore A, Winham S, Wolk A, Woo Y, Wu A, Yan L, Yannoukakos D, Zavaglia K, Zheng W, Ziogas A, Zorn K, Kleibl Z, Easton D, Lawrenson K, DeFazio A, Sellers T, Ramus S, Pearce C, Monteiro A, Cunningham J, Goode E, Schildkraut J, Berchuck A, Chenevix-Trench G, Gayther S, Antoniou A, Pharoah P. Polygenic risk modeling for prediction of epithelial ovarian cancer risk. European Journal Of Human Genetics 2022, 30: 349-362. PMID: 35027648, PMCID: PMC8904525, DOI: 10.1038/s41431-021-00987-7.Peer-Reviewed Original Research
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 activityAllelesMultitrait 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 ResearchThe predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
Lakeman IMM, van den Broek AJ, Vos JAM, Barnes DR, Adlard J, Andrulis IL, Arason A, Arnold N, Arun BK, Balmaña J, Barrowdale D, Benitez J, Borg A, Caldés T, Caligo MA, Chung WK, Claes KBM, Collée J, Couch F, Daly M, Dennis J, Dhawan M, Domchek S, Eeles R, Engel C, Evans D, Feliubadaló L, Foretova L, Friedman E, Frost D, Ganz P, Garber J, Gayther S, Gerdes A, Godwin A, Goldgar D, Hahnen E, Hake C, Hamann U, Hogervorst F, Hooning M, Hopper J, Hulick P, Imyanitov E, Isaacs C, Izatt L, Jakubowska A, James P, Janavicius R, Jensen U, Jiao Y, John E, Joseph V, Karlan B, Kets C, Konstantopoulou I, Kwong A, Legrand C, Leslie G, Lesueur F, Loud J, Lubiński J, Manoukian S, McGuffog L, Miller A, Gomes D, Montagna M, Mouret-Fourme E, Nathanson K, Neuhausen S, Nevanlinna H, Yie J, Olah E, Olopade O, Park S, Parsons M, Peterlongo P, Piedmonte M, Radice P, Rantala J, Rennert G, Risch H, Schmutzler R, Sharma P, Simard J, Singer C, Stadler Z, Stoppa-Lyonnet D, Sutter C, Tan Y, Teixeira M, Teo S, Teulé A, Thomassen M, Thull D, Tischkowitz M, Toland A, Tung N, van Rensburg E, Vega A, Wappenschmidt B, Devilee P, van Asperen C, Bernstein J, Offit K, Easton D, Rookus M, Chenevix-Trench G, Antoniou A, Robson M, Schmidt M. The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant. Genetics In Medicine 2021, 23: 1726-1737. PMID: 34113011, PMCID: PMC8460445, DOI: 10.1038/s41436-021-01198-7.Peer-Reviewed Original ResearchConceptsCBC riskHazard ratioFirst BCC-indexPolygenic risk scoresRisk scoreConfidence intervalsContralateral breast cancer riskBreast cancer polygenic risk scoreBRCA2 pathogenic variantsAge 40 yearsBreast cancer riskMultifactorial risk modelEuropean ancestryModifiers of BRCA1/2Breast cancer risk predictionCancer risk predictionConsortium of InvestigatorsRetrospective seriesInvasive BCPathological characteristicsFamily historyEstrogen receptorHeterozygous BRCA1Cancer riskA multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer
López de Maturana E, Rodríguez JA, Alonso L, Lao O, Molina-Montes E, Martín-Antoniano IA, Gómez-Rubio P, Lawlor R, Carrato A, Hidalgo M, Iglesias M, Molero X, Löhr M, Michalski C, Perea J, O’Rorke M, Barberà VM, Tardón A, Farré A, Muñoz-Bellvís L, Crnogorac-Jurcevic T, Domínguez-Muñoz E, Gress T, Greenhalf W, Sharp L, Arnes L, Cecchini L, Balsells J, Costello E, Ilzarbe L, Kleeff J, Kong B, Márquez M, Mora J, O’Driscoll D, Scarpa A, Ye W, Yu J, García-Closas M, Kogevinas M, Rothman N, Silverman D, Albanes D, Arslan A, Beane-Freeman L, Bracci P, Brennan P, Bueno-de-Mesquita B, Buring J, Canzian F, Du M, Gallinger S, Gaziano J, Goodman P, Gunter M, LeMarchand L, Li D, Neale R, Peters U, Petersen G, Risch H, Sánchez M, Shu X, Thornquist M, Visvanathan K, Zheng W, Chanock S, Easton D, Wolpin B, Stolzenberg-Solomon R, Klein A, Amundadottir L, Marti-Renom M, Real F, Malats N. A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer. Genome Medicine 2021, 13: 15. PMID: 33517887, PMCID: PMC7849104, DOI: 10.1186/s13073-020-00816-4.Peer-Reviewed Original ResearchConceptsSilico functional analysisFunctional analysisPublic genomic informationUnfolded protein responseMeta-analysis p-valueLow-frequency variantsPc locusGWAS hitsGenomic informationPhenotypic varianceProtein responseSpatial autocorrelation analysisER stressMajor regulatorFrequency variantsPancreatic acinar cellsGenetic susceptibilityCandidate variantsFactor interplayComplex diseasesIndependent variantsGWASInherited basisLow p-valuesAcinar cells
2020
Genome-Wide Gene–Diabetes and Gene–Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia
Tang H, Jiang L, Stolzenberg-Solomon RZ, Arslan AA, Beane Freeman LE, Bracci PM, Brennan P, Canzian F, Du M, Gallinger S, Giles GG, Goodman PJ, Kooperberg C, Le Marchand L, Neale RE, Shu XO, Visvanathan K, White E, Zheng W, Albanes D, Andreotti G, Babic A, Bamlet WR, Berndt SI, Blackford A, Bueno-de-Mesquita B, Buring JE, Campa D, Chanock SJ, Childs E, Duell EJ, Fuchs C, Gaziano JM, Goggins M, Hartge P, Hassam MH, Holly EA, Hoover RN, Hung RJ, Kurtz RC, Lee IM, Malats N, Milne RL, Ng K, Oberg AL, Orlow I, Peters U, Porta M, Rabe KG, Rothman N, Scelo G, Sesso HD, Silverman DT, Thompson IM, Tjønneland A, Trichopoulou A, Wactawski-Wende J, Wentzensen N, Wilkens LR, Yu H, Zeleniuch-Jacquotte A, Amundadottir LT, Jacobs EJ, Petersen GM, Wolpin BM, Risch HA, Chatterjee N, Klein AP, Li D, Kraft P, Wei P. Genome-Wide Gene–Diabetes and Gene–Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia. Cancer Epidemiology Biomarkers & Prevention 2020, 29: 1784-1791. PMID: 32546605, PMCID: PMC7483330, DOI: 10.1158/1055-9965.epi-20-0275.Peer-Reviewed Original ResearchConceptsSNP levelGenome-wide association study datasetGenome-wide levelGene-based analysisGWAS summary statisticsJoint effect testsGxE analysisGWAS top hitsPopulation substructureSignificant GxE interactionGene levelGene-environment interaction analysisAdditional genetic factorsTop hitsEnvironmental variablesGenetic variantsDiabetes/obesityGxE interactionsPancreatic cancerStudy sitesGenetic factorsMajor modifiable risk factorHit regionsModifiable risk factorsInteraction analysis