2021
A 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
2018
rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology
Kelemen LE, Earp M, Fridley BL, Chenevix-Trench G, Group O, Fasching PA, Beckmann MW, Ekici AB, Hein A, Lambrechts D, Lambrechts S, Van Nieuwenhuysen E, Vergote I, Rossing MA, Doherty JA, Chang-Claude J, Behrens S, Moysich KB, Cannioto R, Lele S, Odunsi K, Goodman MT, Shvetsov YB, Thompson PJ, Wilkens LR, Dörk T, Antonenkova N, Bogdanova N, Hillemanns P, Runnebaum IB, du Bois A, Harter P, Heitz F, Schwaab I, Butzow R, Pelttari LM, Nevanlinna H, Modugno F, Edwards RP, Kelley JL, Ness RB, Karlan BY, Lester J, Orsulic S, Walsh C, Kjaer SK, Jensen A, Cunningham JM, Vierkant RA, Giles GG, Bruinsma F, Southey MC, Hildebrandt MAT, Liang D, Lu K, Wu X, Sellers TA, Levine DA, Schildkraut JM, Iversen ES, Terry KL, Cramer DW, Tworoger SS, Poole EM, Bandera EV, Olson SH, Orlow I, Thomsen L, Bjorge L, Krakstad C, Tangen IL, Kiemeney LA, Aben KKH, Massuger LFAG, van Altena AM, Pejovic T, Bean Y, Kellar M, Cook LS, Le ND, Brooks-Wilson A, Gronwald J, Cybulski C, Jakubowska A, Lubiński J, Wentzensen N, Brinton LA, Lissowska J, Hogdall E, Engelholm SA, Hogdall C, Lundvall L, Nedergaard L, Pharoah PDP, Dicks E, Song H, Tyrer JP, McNeish I, Siddiqui N, Carty K, Glasspool R, Paul J, Campbell IG, Eccles D, Whittemore AS, McGuire V, Rothstein JH, Sieh W, Narod SA, Phelan CM, McLaughlin JR, Risch HA, Anton-Culver H, Ziogas A, Menon U, Gayther SA, Gentry-Maharaj A, Ramus SJ, Wu AH, Pearce CL, Lee AW, Pike MC, Kupryjanczyk J, Podgorska A, Plisiecka-Halasa J, Sawicki W, Goode EL, Berchuck A, Consortium O. rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology. International Journal Of Molecular Sciences 2018, 19: 2473. PMID: 30134598, PMCID: PMC6163881, DOI: 10.3390/ijms19092473.Peer-Reviewed Original ResearchAdenocarcinoma, MucinousCase-Control StudiesFemaleGene Expression Regulation, NeoplasticGenetic Association StudiesHumansHydro-LyasesLogistic ModelsMiddle AgedOdds RatioOvarian NeoplasmsPolymorphism, Single NucleotideProteinsQuantitative Trait LociRiskRNA, AntisenseSignal TransductionThymidylate SynthaseIdentification of nine new susceptibility loci for endometrial cancer
O’Mara T, Glubb DM, Amant F, Annibali D, Ashton K, Attia J, Auer PL, Beckmann MW, Black A, Bolla MK, Brauch H, Brenner H, Brinton L, Buchanan DD, Burwinkel B, Chang-Claude J, Chanock SJ, Chen C, Chen MM, Cheng THT, Clarke CL, Clendenning M, Cook LS, Couch FJ, Cox A, Crous-Bous M, Czene K, Day F, Dennis J, Depreeuw J, Doherty JA, Dörk T, Dowdy SC, Dürst M, Ekici AB, Fasching PA, Fridley BL, Friedenreich CM, Fritschi L, Fung J, García-Closas M, Gaudet MM, Giles GG, Goode EL, Gorman M, Haiman CA, Hall P, Hankison SE, Healey CS, Hein A, Hillemanns P, Hodgson S, Hoivik EA, Holliday EG, Hopper JL, Hunter DJ, Jones A, Krakstad C, Kristensen VN, Lambrechts D, Marchand LL, Liang X, Lindblom A, Lissowska J, Long J, Lu L, Magliocco AM, Martin L, McEvoy M, Meindl A, Michailidou K, Milne RL, Mints M, Montgomery GW, Nassir R, Olsson H, Orlow I, Otton G, Palles C, Perry JRB, Peto J, Pooler L, Prescott J, Proietto T, Rebbeck TR, Risch HA, Rogers PAW, Rübner M, Runnebaum I, Sacerdote C, Sarto GE, Schumacher F, Scott RJ, Setiawan VW, Shah M, Sheng X, Shu XO, Southey MC, Swerdlow AJ, Tham E, Trovik J, Turman C, Tyrer JP, Vachon C, VanDen Berg D, Vanderstichele A, Wang Z, Webb PM, Wentzensen N, Werner HMJ, Winham SJ, Wolk A, Xia L, Xiang YB, Yang HP, Yu H, Zheng W, Pharoah PDP, Dunning AM, Kraft P, De Vivo I, Tomlinson I, Easton DF, Spurdle AB, Thompson DJ. Identification of nine new susceptibility loci for endometrial cancer. Nature Communications 2018, 9: 3166. PMID: 30093612, PMCID: PMC6085317, DOI: 10.1038/s41467-018-05427-7.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesCandidate causal genesCausal genesNovel genome-wide significant lociRisk lociEndometrial cancer risk lociGenome-wide significant lociExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisSignal transduction proteinsCancer risk lociNew susceptibility lociTransduction proteinsSignificant lociLocus analysisNegative regulatorAssociation studiesFemale reproductive tractSusceptibility lociLoci associateLociGenesDecreased expressionReproductive tractRisk alleles
2016
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
Kar SP, Beesley J, Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, Lawrenson K, Lindstrom S, Ramus SJ, Thompson DJ, Investigators A, Kibel AS, Dansonka-Mieszkowska A, Michael A, Dieffenbach AK, Gentry-Maharaj A, Whittemore AS, Wolk A, Monteiro A, Peixoto A, Kierzek A, Cox A, Rudolph A, Gonzalez-Neira A, Wu AH, Lindblom A, Swerdlow A, Study A, BioResource A, Ziogas A, Ekici AB, Burwinkel B, Karlan BY, Nordestgaard BG, Blomqvist C, Phelan C, McLean C, Pearce CL, Vachon C, Cybulski C, Slavov C, Stegmaier C, Maier C, Ambrosone CB, Høgdall CK, Teerlink CC, Kang D, Tessier DC, Schaid DJ, Stram DO, Cramer DW, Neal DE, Eccles D, Flesch-Janys D, Edwards DR, Wokozorczyk D, Levine DA, Yannoukakos D, Sawyer EJ, Bandera EV, Poole EM, Goode EL, Khusnutdinova E, Høgdall E, Song F, Bruinsma F, Heitz F, Modugno F, Hamdy FC, Wiklund F, Giles GG, Olsson H, Wildiers H, Ulmer HU, Pandha H, Risch HA, Darabi H, Salvesen HB, Nevanlinna H, Gronberg H, Brenner H, Brauch H, Anton-Culver H, Song H, Lim HY, McNeish I, Campbell I, Vergote I, Gronwald J, Lubiński J, Stanford JL, Benítez J, Doherty JA, Permuth JB, Chang-Claude J, Donovan JL, Dennis J, Schildkraut JM, Schleutker J, Hopper JL, Kupryjanczyk J, Park JY, Figueroa J, Clements JA, Knight JA, Peto J, Cunningham JM, Pow-Sang J, Batra J, Czene K, Lu KH, Herkommer K, Khaw KT, Investigators K, Matsuo K, Muir K, Offitt K, Chen K, Moysich KB, Aittomäki K, Odunsi K, Kiemeney LA, Massuger LF, Fitzgerald LM, Cook LS, Cannon-Albright L, Hooning MJ, Pike MC, Bolla MK, Luedeke M, Teixeira MR, Goodman MT, Schmidt MK, Riggan M, Aly M, Rossing MA, Beckmann MW, Moisse M, Sanderson M, Southey MC, Jones M, Lush M, Hildebrandt MA, Hou MF, Schoemaker MJ, Garcia-Closas M, Bogdanova N, Rahman N, Investigators N, Le ND, Orr N, Wentzensen N, Pashayan N, Peterlongo P, Guénel P, Brennan P, Paulo P, Webb PM, Broberg P, Fasching PA, Devilee P, Wang Q, Cai Q, Li Q, Kaneva R, Butzow R, Kopperud RK, Schmutzler RK, Stephenson RA, MacInnis RJ, Hoover RN, Winqvist R, Ness R, Milne RL, Travis RC, Benlloch S, Olson SH, McDonnell SK, Tworoger SS, Maia S, Berndt S, Lee SC, Teo SH, Thibodeau SN, Bojesen SE, Gapstur SM, Kjær SK, Pejovic T, Tammela TL, Network T, consortium T, Dörk T, Brüning T, Wahlfors T, Key TJ, Edwards TL, Menon U, Hamann U, Mitev V, Kosma VM, Setiawan VW, Kristensen V, Arndt V, Vogel W, Zheng W, Sieh W, Blot WJ, Kluzniak W, Shu XO, Gao YT, Schumacher F, Freedman ML, Berchuck A, Dunning AM, Simard J, Haiman CA, Spurdle A, Sellers TA, Hunter DJ, Henderson BE, Kraft P, Chanock SJ, Couch FJ, Hall P, Gayther SA, Easton DF, Chenevix-Trench G, Eeles R, Pharoah PD, Lambrechts D. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. Cancer Discovery 2016, 6: 1052-1067. PMID: 27432226, PMCID: PMC5010513, DOI: 10.1158/2159-8290.cd-15-1227.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCase-Control StudiesChromosome MappingDatasets as TopicEnhancer Elements, GeneticFemaleGene Regulatory NetworksGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMeta-Analysis as TopicOrgan SpecificityOvarian NeoplasmsPolymorphism, Single NucleotideProstatic NeoplasmsQuantitative Trait LociSignal TransductionConceptsCancer risk lociRisk lociSpecific expression quantitative trait lociExpression quantitative trait lociGenome-wide association studiesProstate cancer risk lociQuantitative trait lociNew risk lociMeta-analysis data setsTrait lociTarget genesGenetic basisNew lociCancer typesDeath receptorsPathway analysisInteraction annotationsAssociation studiesLociSignificant enrichmentIndex variantsEuropean ancestryAdditional regionsGenesSecond cancer typesGermline 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 loci
2014
Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study
Lee AW, Tyrer JP, Doherty JA, Stram DA, Kupryjanczyk J, Dansonka-Mieszkowska A, Plisiecka-Halasa J, Spiewankiewicz B, Myers EJ, Study A, Group A, Chenevix-Trench G, Fasching PA, Beckmann MW, Ekici AB, Hein A, Vergote I, Van Nieuwenhuysen E, Lambrechts D, Wicklund KG, Eilber U, Wang-Gohrke S, Chang-Claude J, Rudolph A, Sucheston-Campbell L, Odunsi K, Moysich KB, Shvetsov YB, Thompson PJ, Goodman MT, Wilkens LR, Dörk T, Hillemanns P, Dürst M, Runnebaum IB, Bogdanova N, Pelttari LM, Nevanlinna H, Leminen A, Edwards RP, Kelley JL, Harter P, Schwaab I, Heitz F, du Bois A, Orsulic S, Lester J, Walsh C, Karlan BY, Hogdall E, Kjaer SK, Jensen A, Vierkant RA, Cunningham JM, Goode EL, Fridley BL, Southey MC, Giles GG, Bruinsma F, Wu X, Hildebrandt MA, Lu K, Liang D, Bisogna M, Levine DA, Weber RP, Schildkraut JM, Iversen ES, Berchuck A, Terry KL, Cramer DW, Tworoger SS, Poole EM, Olson SH, Orlow I, Bandera EV, Bjorge L, Tangen IL, Salvesen HB, Krakstad C, Massuger LF, Kiemeney LA, Aben KK, van Altena AM, Bean Y, Pejovic T, Kellar M, Le ND, Cook LS, Kelemen LE, Brooks-Wilson A, Lubinski J, Gronwald J, Cybulski C, Jakubowska A, Wentzensen N, Brinton LA, Lissowska J, Yang H, Nedergaard L, Lundvall L, Hogdall C, Song H, Campbell IG, Eccles D, Glasspool R, Siddiqui N, Carty K, Paul J, McNeish IA, Sieh W, McGuire V, Rothstein JH, Whittemore AS, McLaughlin JR, Risch HA, Phelan CM, Anton-Culver H, Ziogas A, Menon U, Ramus SJ, Gentry-Maharaj A, Harrington P, Pike MC, Modugno F, Rossing MA, Ness RB, Pharoah PD, Stram DO, Wu AH, Pearce CL. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study. Gynecologic Oncology 2014, 136: 542-548. PMID: 25528498, PMCID: PMC4892108, DOI: 10.1016/j.ygyno.2014.12.017.Peer-Reviewed Original ResearchConceptsOvarian cancer riskOvarian Cancer StudyCancer riskGene-level associationsOnly modest associationsUnconditional logistic regressionCancer studiesHormone-related diseasesPathway genesGonadotropin hypothesisEtiologic roleGenome-wide significant associationOvarian cancerProstate cancerLarger sample sizeGonadotropinSignificant associationDisease riskModest associationLogistic regressionGene-level testsHigh-penetrance susceptibility genesCandidate gene studiesStrong genetic basisUnderstanding of biologyRisk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10
Charbonneau B, Block MS, Bamlet WR, Vierkant RA, Kalli KR, Fogarty Z, Rider DN, Sellers TA, Tworoger SS, Poole E, Risch HA, Salvesen HB, Kiemeney LA, Baglietto L, Giles GG, Severi G, Trabert B, Wentzensen N, Chenevix-Trench G, group F, Whittemore AS, Sieh W, Chang-Claude J, Bandera EV, Orlow I, Terry K, Goodman MT, Thompson PJ, Cook LS, Rossing MA, Ness RB, Narod SA, Kupryjanczyk J, Lu K, Butzow R, Dörk T, Pejovic T, Campbell I, Le ND, Bunker CH, Bogdanova N, Runnebaum IB, Eccles D, Paul J, Wu AH, Gayther SA, Hogdall E, Heitz F, Kaye SB, Karlan BY, Anton-Culver H, Gronwald J, Hogdall CK, Lambrechts D, Fasching PA, Menon U, Schildkraut J, Pearce CL, Levine DA, Kjaer SK, Cramer D, Flanagan JM, Phelan CM, Brown R, Massuger LF, Song H, Doherty JA, Krakstad C, Liang D, Odunsi K, Berchuck A, Jensen A, Lubiński J, Nevanlinna H, Bean YT, Lurie G, Ziogas A, Walsh C, Despierre E, Brinton L, Hein A, Rudolph A, Dansonka-Mieszkowska A, Olson SH, Harter P, Tyrer J, Vitonis AF, Brooks-Wilson A, Aben KK, Pike MC, Ramus SJ, Wik E, Cybulski C, Lin J, Sucheston L, Edwards R, McGuire V, Lester J, du Bois A, Lundvall L, Wang-Gohrke S, Szafron LM, Lambrechts S, Yang H, Beckmann MW, Pelttari LM, Van Altena AM, van den Berg D, Halle MK, Gentry-Maharaj A, Schwaab I, Chandran U, Menkiszak J, Ekici AB, Wilkens LR, Leminen A, Modugno F, Friel G, Rothstein JH, Vergote I, Garcia-Closas M, Hildebrandt MA, Sobiczewski P, Kelemen LE, Pharoah PD, Moysich K, Knutson KL, Cunningham JM, Fridley BL, Goode EL. Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10. Cancer Research 2014, 74: 852-861. PMID: 24272484, PMCID: PMC3946482, DOI: 10.1158/0008-5472.can-13-1051.Peer-Reviewed Original ResearchConceptsOvarian cancerNF-κB pathwaySingle nucleotide polymorphismsRisk factorsClear cell ovarian cancerEpidemiologic risk factorsOvarian cancer riskOvarian Cancer Association ConsortiumOvarian cancer associationRisk of endometriosisAlters riskBorderline tumorsClear cellsInterleukin-1αMissense single nucleotide polymorphismCancer riskProinflammatory genesCancer associationNF-κBCancerImportant mediatorDistinct genetic etiologiesControl casesExact mechanismGenotype analysisAxonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data
Tang H, Wei P, Duell EJ, Risch HA, Olson SH, Bueno-de-Mesquita HB, Gallinger S, Holly EA, Petersen G, Bracci PM, McWilliams RR, Jenab M, Riboli E, Tjønneland A, Boutron-Ruault MC, Kaaks R, Trichopoulos D, Panico S, Sund M, Peeters PH, Khaw KT, Amos CI, Li D. Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data. Carcinogenesis 2014, 35: 1039-1045. PMID: 24419231, PMCID: PMC4004205, DOI: 10.1093/carcin/bgu010.Peer-Reviewed Original ResearchConceptsIngenuity Pathway AnalysisKEGG pathwaysSingle nucleotide polymorphism (SNP) levelAxonal guidanceGenome-wide levelGene ontology pathwaysSalivary secretion pathwaysSlit/RoboGenes/SNPsOntology pathwaysPolymorphism levelSecretion pathwayGWAS dataGene setsPancreatic Cancer Case-Control ConsortiumCanonical pathwaysPathway analysisAxon guidanceGenesSNPsRegion SNPsPathwayIPA analysisPancreatic cancerDiscovery studies