2024
Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions
Dareng E, Coetzee S, Tyrer J, Peng P, Rosenow W, Chen S, Davis B, Dezem F, Seo J, Nameki R, Reyes A, Aben K, Anton-Culver H, Antonenkova N, Aravantinos G, Bandera E, Freeman L, Beckmann M, Beeghly-Fadiel A, Benitez J, Bernardini M, Bjorge L, Black A, Bogdanova N, Bolton K, Brenton J, Budzilowska A, Butzow R, Cai H, Campbell I, Cannioto R, Chang-Claude J, Chanock S, Chen K, Chenevix-Trench G, Group A, Chiew Y, Cook L, DeFazio A, Dennis J, Doherty J, Dörk T, du Bois A, Dürst M, Eccles D, Ene G, Fasching P, Flanagan J, Fortner R, Fostira F, Gentry-Maharaj A, Giles G, Goodman M, Gronwald J, Haiman C, Håkansson N, Heitz F, Hildebrandt M, Høgdall E, Høgdall C, Huang R, Jensen A, Jones M, Kang D, Karlan B, Karnezis A, Kelemen L, Kennedy C, Khusnutdinova E, Kiemeney L, Kjaer S, Kupryjanczyk J, Labrie M, Lambrechts D, Larson M, Le N, Lester J, Li L, Lubiński J, Lush M, Marks J, Matsuo K, May T, McLaughlin J, McNeish I, Menon U, Missmer S, Modugno F, Moffitt M, Monteiro A, Moysich K, Narod S, Nguyen-Dumont T, Odunsi K, Olsson H, Onland-Moret N, Park S, Pejovic T, Permuth J, Piskorz A, Prokofyeva D, Riggan M, Risch H, Rodríguez-Antona C, Rossing M, Sandler D, Setiawan V, Shan K, Song H, Southey M, Steed H, Sutphen R, Swerdlow A, Teo S, Terry K, Thompson P, Thomsen L, Titus L, Trabert B, Travis R, Tworoger S, Valen E, Van Nieuwenhuysen E, Edwards D, Vierkant R, Webb P, Group O, Weinberg C, Weise R, Wentzensen N, White E, Winham S, Wolk A, Woo Y, Wu A, Yan L, Yannoukakos D, Zeinomar N, Zheng W, Ziogas A, Berchuck A, Goode E, Huntsman D, Pearce C, Ramus S, Sellers T, Consortium T, Freedman M, Lawrenson K, Schildkraut J, Hazelett D, Plummer J, Kar S, Jones M, Pharoah P, Gayther S. Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions. American Journal Of Human Genetics 2024, 111: 1061-1083. PMID: 38723632, PMCID: PMC11179261, DOI: 10.1016/j.ajhg.2024.04.011.Peer-Reviewed Original ResearchTranscriptome-wide association studyRisk lociAssociation studiesTranscription factor ChIP-seqSusceptibility genesGenome-wide association analysisGenome-wide association studiesCausal risk variantsControls of European originTranscriptome-wide associationEpithelial ovarian cancerVariant Effect PredictorIntegrative multi-omics analysisMulti-omics analysisChIP-seqChromatin marksGenomic regionsFine-mappingSusceptibility lociInteractome analysisAssociation analysisEpithelial ovarian cancer histotypesRisk variantsTissue-specificLoci
2023
Genome-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 cancersHeritability
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 malignancyGenome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer
Lin Y, Nakatochi M, Hosono Y, Ito H, Kamatani Y, Inoko A, Sakamoto H, Kinoshita F, Kobayashi Y, Ishii H, Ozaka M, Sasaki T, Matsuyama M, Sasahira N, Morimoto M, Kobayashi S, Fukushima T, Ueno M, Ohkawa S, Egawa N, Kuruma S, Mori M, Nakao H, Adachi Y, Okuda M, Osaki T, Kamiya S, Wang C, Hara K, Shimizu Y, Miyamoto T, Hayashi Y, Ebi H, Kohmoto T, Imoto I, Kasugai Y, Murakami Y, Akiyama M, Ishigaki K, Matsuda K, Hirata M, Shimada K, Okusaka T, Kawaguchi T, Takahashi M, Watanabe Y, Kuriki K, Kadota A, Okada R, Mikami H, Takezaki T, Suzuki S, Yamaji T, Iwasaki M, Sawada N, Goto A, Kinoshita K, Fuse N, Katsuoka F, Shimizu A, Nishizuka SS, Tanno K, Suzuki K, Okada Y, Horikoshi M, Yamauchi T, Kadowaki T, Yu H, Zhong J, Amundadottir LT, Doki Y, Ishii H, Eguchi H, Bogumil D, Haiman CA, Le Marchand L, Mori M, Risch H, Setiawan VW, Tsugane S, Wakai K, Yoshida T, Matsuda F, Kubo M, Kikuchi S, Matsuo K. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer. Nature Communications 2020, 11: 3175. PMID: 32581250, PMCID: PMC7314803, DOI: 10.1038/s41467-020-16711-w.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide significant lociLead single nucleotide polymorphismsGenome-wide association studiesGene variantsMeta-analysis identifiesEast Asian ancestryEast Asian originSignificant lociRisk lociFunctional analysisAssociation studiesPancreatic cancer susceptibilityRisk variantsNucleotide polymorphismsCell linesGene risk variantsCancer susceptibilityLociAsian ancestryKRAS activityAsian originVariantsPancreatic cancerPopulationFine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S, Pooley KA, Dennis J, Michailidou K, Turman C, Soucy P, Lemaçon A, Lush M, Tyrer JP, Ghoussaini M, Moradi Marjaneh M, Jiang X, Agata S, Aittomäki K, Alonso MR, Andrulis IL, Anton-Culver H, Antonenkova NN, Arason A, Arndt V, Aronson KJ, Arun BK, Auber B, Auer PL, Azzollini J, Balmaña J, Barkardottir RB, Barrowdale D, Beeghly-Fadiel A, Benitez J, Bermisheva M, Białkowska K, Blanco AM, Blomqvist C, Blot W, Bogdanova NV, Bojesen SE, Bolla MK, Bonanni B, Borg A, Bosse K, Brauch H, Brenner H, Briceno I, Brock IW, Brooks-Wilson A, Brüning T, Burwinkel B, Buys SS, Cai Q, Caldés T, Caligo MA, Camp NJ, Campbell I, Canzian F, Carroll JS, Carter BD, Castelao JE, Chiquette J, Christiansen H, Chung WK, Claes KBM, Clarke CL, Collée J, Cornelissen S, Couch F, Cox A, Cross S, Cybulski C, Czene K, Daly M, de la Hoya M, Devilee P, Diez O, Ding Y, Dite G, Domchek S, Dörk T, dos-Santos-Silva I, Droit A, Dubois S, Dumont M, Duran M, Durcan L, Dwek M, Eccles D, Engel C, Eriksson M, Evans D, Fasching P, Fletcher O, Floris G, Flyger H, Foretova L, Foulkes W, Friedman E, Fritschi L, Frost D, Gabrielson M, Gago-Dominguez M, Gambino G, Ganz P, Gapstur S, Garber J, García-Sáenz J, Gaudet M, Georgoulias V, Giles G, Glendon G, Godwin A, Goldberg M, Goldgar D, González-Neira A, Tibiletti M, Greene M, Grip M, Gronwald J, Grundy A, Guénel P, Hahnen E, Haiman C, Håkansson N, Hall P, Hamann U, Harrington P, Hartikainen J, Hartman M, He W, Healey C, Heemskerk-Gerritsen B, Heyworth J, Hillemanns P, Hogervorst F, Hollestelle A, Hooning M, Hopper J, Howell A, Huang G, Hulick P, Imyanitov E, Isaacs C, Iwasaki M, Jager A, Jakimovska M, Jakubowska A, James P, Janavicius R, Jankowitz R, John E, Johnson N, Jones M, Jukkola-Vuorinen A, Jung A, Kaaks R, Kang D, Kapoor P, Karlan B, Keeman R, Kerin M, Khusnutdinova E, Kiiski J, Kirk J, Kitahara C, Ko Y, Konstantopoulou I, Kosma V, Koutros S, Kubelka-Sabit K, Kwong A, Kyriacou K, Laitman Y, Lambrechts D, Lee E, Leslie G, Lester J, Lesueur F, Lindblom A, Lo W, Long J, Lophatananon A, Loud J, Lubiński J, MacInnis R, Maishman T, Makalic E, Mannermaa A, Manoochehri M, Manoukian S, Margolin S, Martinez M, Matsuo K, Maurer T, Mavroudis D, Mayes R, McGuffog L, McLean C, Mebirouk N, Meindl A, Miller A, Miller N, Montagna M, Moreno F, Muir K, Mulligan A, Muñoz-Garzon V, Muranen T, Narod S, Nassir R, Nathanson K, Neuhausen S, Nevanlinna H, Neven P, Nielsen F, Nikitina-Zake L, Norman A, Offit K, Olah E, Olopade O, Olsson H, Orr N, Osorio A, Pankratz V, Papp J, Park S, Park-Simon T, Parsons M, Paul J, Pedersen I, Peissel B, Peshkin B, Peterlongo P, Peto J, Plaseska-Karanfilska D, Prajzendanc K, Prentice R, Presneau N, Prokofyeva D, Pujana M, Pylkäs K, Radice P, Ramus S, Rantala J, Rau-Murthy R, Rennert G, Risch H, Robson M, Romero A, Rossing M, Saloustros E, Sánchez-Herrero E, Sandler D, Santamariña M, Saunders C, Sawyer E, Scheuner M, Schmidt D, Schmutzler R, Schneeweiss A, Schoemaker M, Schöttker B, Schürmann P, Scott C, Scott R, Senter L, Seynaeve C, Shah M, Sharma P, Shen C, Shu X, Singer C, Slavin T, Smichkoska S, Southey M, Spinelli J, Spurdle A, Stone J, Stoppa-Lyonnet D, Sutter C, Swerdlow A, Tamimi R, Tan Y, Tapper W, Taylor J, Teixeira M, Tengström M, Teo S, Terry M, Teulé A, Thomassen M, Thull D, Tischkowitz M, Toland A, Tollenaar R, Tomlinson I, Torres D, Torres-Mejía G, Troester M, Truong T, Tung N, Tzardi M, Ulmer H, Vachon C, van Asperen C, van der Kolk L, van Rensburg E, Vega A, Viel A, Vijai J, Vogel M, Wang Q, Wappenschmidt B, Weinberg C, Weitzel J, Wendt C, Wildiers H, Winqvist R, Wolk A, Wu A, Yannoukakos D, Zhang Y, Zheng W, Hunter D, Pharoah P, Chang-Claude J, García-Closas M, Schmidt M, Milne R, Kristensen V, French J, Edwards S, Antoniou A, Chenevix-Trench G, Simard J, Easton D, Kraft P, Dunning A. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics 2020, 52: 56-73. PMID: 31911677, PMCID: PMC6974400, DOI: 10.1038/s41588-019-0537-1.Peer-Reviewed Original ResearchConceptsCausal variantsTranscription factorsTarget genesActive gene regulatory regionsHigh-confidence target genesGenomic feature annotationsGenome-wide association studiesBreast cancer risk variantsGene regulatory regionsCredible causal variantsGene ontology pathwaysChromatin interactionsFunctional annotationGenomic regionsOntology pathwaysRegulatory regionsGenomic featuresCancer driversGene expressionAssociation studiesAssociation analysisGenesLinkage disequilibriumRisk variantsHigh posterior probability
2019
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
Ferreira MA, Gamazon ER, Al-Ejeh F, Aittomäki K, Andrulis IL, Anton-Culver H, Arason A, Arndt V, Aronson KJ, Arun BK, Asseryanis E, Azzollini J, Balmaña J, Barnes DR, Barrowdale D, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Białkowska K, Blomqvist C, Bogdanova NV, Bojesen SE, Bolla MK, Borg A, Brauch H, Brenner H, Broeks A, Burwinkel B, Caldés T, Caligo MA, Campa D, Campbell I, Canzian F, Carter J, Carter BD, Castelao JE, Chang-Claude J, Chanock SJ, Christiansen H, Chung WK, Claes KBM, Clarke CL, Couch F, Cox A, Cross S, Czene K, Daly M, de la Hoya M, Dennis J, Devilee P, Diez O, Dörk T, Dunning A, Dwek M, Eccles D, Ejlertsen B, Ellberg C, Engel C, Eriksson M, Fasching P, Fletcher O, Flyger H, Friedman E, Frost D, Gabrielson M, Gago-Dominguez M, Ganz P, Gapstur S, Garber J, García-Closas M, García-Sáenz J, Gaudet M, Giles G, Glendon G, Godwin A, Goldberg M, Goldgar D, González-Neira A, Greene M, Gronwald J, Guénel P, Haiman C, Hall P, Hamann U, He W, Heyworth J, Hogervorst F, Hollestelle A, Hoover R, Hopper J, Hulick P, Humphreys K, Imyanitov E, Isaacs C, Jakimovska M, Jakubowska A, James P, Janavicius R, Jankowitz R, John E, Johnson N, Joseph V, Karlan B, Khusnutdinova E, Kiiski J, Ko Y, Jones M, Konstantopoulou I, Kristensen V, Laitman Y, Lambrechts D, Lazaro C, Leslie G, Lester J, Lesueur F, Lindström S, Long J, Loud J, Lubiński J, Makalic E, Mannermaa A, Manoochehri M, Margolin S, Maurer T, Mavroudis D, McGuffog L, Meindl A, Menon U, Michailidou K, Miller A, Montagna M, Moreno F, Moserle L, Mulligan A, Nathanson K, Neuhausen S, Nevanlinna H, Nevelsteen I, Nielsen F, Nikitina-Zake L, Nussbaum R, Offit K, Olah E, Olopade O, Olsson H, Osorio A, Papp J, Park-Simon T, Parsons M, Pedersen I, Peixoto A, Peterlongo P, Pharoah P, Plaseska-Karanfilska D, Poppe B, Presneau N, Radice P, Rantala J, Rennert G, Risch H, Saloustros E, Sanden K, Sawyer E, Schmidt M, Schmutzler R, Sharma P, Shu X, Simard J, Singer C, Soucy P, Southey M, Spinelli J, Spurdle A, Stone J, Swerdlow A, Tapper W, Taylor J, Teixeira M, Terry M, Teulé A, Thomassen M, Thöne K, Thull D, Tischkowitz M, Toland A, Torres D, Truong T, Tung N, Vachon C, van Asperen C, van den Ouweland A, van Rensburg E, Vega A, Viel A, Wang Q, Wappenschmidt B, Weitzel J, Wendt C, Winqvist R, Yang X, Yannoukakos D, Ziogas A, Kraft P, Antoniou A, Zheng W, Easton D, Milne R, Beesley J, Chenevix-Trench G. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nature Communications 2019, 10: 1741. PMID: 30988301, PMCID: PMC6465407, DOI: 10.1038/s41467-018-08053-5.Peer-Reviewed Original ResearchConceptsExpression quantitative trait lociGenome-wide association studiesTarget genesMultiple expression quantitative trait lociBreast cancer risk variantsPrevious genome-wide association studyQuantitative trait lociGenome-wide associationGene-based testsBreast cancerBreast cancer susceptibility lociCancer susceptibility lociRisk-associated variantsImmune cellsTrait lociTranscriptome studiesRisk lociGene expressionAssociation studiesOverall breast cancer riskSusceptibility lociMultiple tissuesBreast cancer riskNegative breast cancerRisk variants
2018
Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility
Earp M, Tyrer JP, Winham SJ, Lin HY, Chornokur G, Dennis J, Aben KKH, Anton‐Culver H, Antonenkova N, Bandera EV, Bean YT, Beckmann MW, Bjorge L, Bogdanova N, Brinton LA, Brooks-Wilson A, Bruinsma F, Bunker CH, Butzow R, Campbell IG, Carty K, Chang-Claude J, Cook LS, Cramer DW, Cunningham JM, Cybulski C, Dansonka-Mieszkowska A, Despierre E, Doherty JA, Dörk T, du Bois A, Dürst M, Easton DF, Eccles DM, Edwards RP, Ekici AB, Fasching PA, Fridley BL, Gentry-Maharaj A, Giles GG, Glasspool R, Goodman MT, Gronwald J, Harter P, Hein A, Heitz F, Hildebrandt MAT, Hillemanns P, Hogdall CK, Høgdall E, Hosono S, Iversen ES, Jakubowska A, Jensen A, Ji BT, Jung AY, Karlan BY, Kellar M, Kiemeney LA, Lim B, Kjaer SK, Krakstad C, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le ND, Lele S, Lester J, Levine DA, Li Z, Liang D, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger LFAG, Matsuo K, McGuire V, McLaughlin JR, McNeish I, Menon U, Milne RL, Modugno F, Moysich KB, Ness RB, Nevanlinna H, Odunsi K, Olson SH, Orlow I, Orsulic S, Paul J, Pejovic T, Pelttari LM, Permuth JB, Pike MC, Poole EM, Rosen B, Rossing MA, Rothstein JH, Runnebaum IB, Rzepecka IK, Schernhammer E, Schwaab I, Shu XO, Shvetsov YB, Siddiqui N, Sieh W, Song H, Southey MC, Spiewankiewicz B, Sucheston-Campbell L, Tangen IL, Teo SH, Terry KL, Thompson PJ, Thomsen L, Tworoger SS, van Altena AM, Vergote I, Thomsen L, Vierkant RA, Walsh CS, Wang-Gohrke S, Wentzensen N, Whittemore AS, Wicklund KG, Wilkens LR, Woo YL, Wu AH, Wu X, Xiang YB, Yang H, Zheng W, Ziogas A, Lee AW, Pearce CL, Berchuck A, Schildkraut JM, Ramus SJ, Monteiro ANA, Narod SA, Sellers TA, Gayther SA, Kelemen LE, Chenevix-Trench G, Risch HA, Pharoah PDP, Goode EL, Phelan CM. Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility. PLOS ONE 2018, 13: e0197561. PMID: 29979793, PMCID: PMC6034790, DOI: 10.1371/journal.pone.0197561.Peer-Reviewed Original ResearchConceptsFunctional annotationSmall GTPasesExpression quantitative trait lociPotential transcriptional regulatory functionTranscriptional regulatory functionQuantitative trait lociEpithelial ovarian cancer susceptibilitySmall GTPase genesSuper-enhancer regionsVesicle transportTrait lociGTPase genesSmall GTPSignal transductionCell motilityGenotype arraysRegulatory functionsNormal ovarian physiologyOvarian cancer susceptibilityVariants of interestRisk variantsEOC riskGermline variationGenesGTPases
2017
Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci
Kar SP, Adler E, Tyrer J, Hazelett D, Anton-Culver H, Bandera EV, Beckmann MW, Berchuck A, Bogdanova N, Brinton L, Butzow R, Campbell I, Carty K, Chang-Claude J, Cook LS, Cramer DW, Cunningham JM, Dansonka-Mieszkowska A, Doherty JA, Dörk T, Dürst M, Eccles D, Fasching PA, Flanagan J, Gentry-Maharaj A, Glasspool R, Goode EL, Goodman MT, Gronwald J, Heitz F, Hildebrandt MA, Høgdall E, Høgdall CK, Huntsman DG, Jensen A, Karlan BY, Kelemen LE, Kiemeney LA, Kjaer SK, Kupryjanczyk J, Lambrechts D, Levine DA, Li Q, Lissowska J, Lu KH, Lubiński J, Massuger LF, McGuire V, McNeish I, Menon U, Modugno F, Monteiro AN, Moysich KB, Ness RB, Nevanlinna H, Paul J, Pearce CL, Pejovic T, Permuth JB, Phelan C, Pike MC, Poole EM, Ramus SJ, Risch HA, Rossing MA, Salvesen HB, Schildkraut JM, Sellers TA, Sherman M, Siddiqui N, Sieh W, Song H, Southey M, Terry KL, Tworoger SS, Walsh C, Wentzensen N, Whittemore AS, Wu AH, Yang H, Zheng W, Ziogas A, Freedman ML, Gayther SA, Pharoah PD, Lawrenson K. Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. British Journal Of Cancer 2017, 116: 524-535. PMID: 28103614, PMCID: PMC5318969, DOI: 10.1038/bjc.2016.426.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Ovarian EpithelialCase-Control StudiesCell Line, TumorCell Transformation, NeoplasticCystadenocarcinoma, SerousFemaleGene AmplificationGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMeta-Analysis as TopicMicroarray AnalysisNeoplasms, Glandular and EpithelialOvarian NeoplasmsPolymorphism, Single NucleotideConceptsGenome-wide association studiesTarget genesTranscription factorsRisk lociOvarian cancer susceptibility lociCancer risk lociDifferential gene expressionCancer susceptibility lociMolecular Signatures DatabaseShRNA-mediated silencingGene setsEnrichment analysisGene expressionTranscriptomic perturbationsAssociation studiesSusceptibility lociGenesLociOvarian cancer susceptibilityRisk variantsAgnostic evaluationCell of originCancer susceptibilityBiological mechanismsPathway
2016
Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, Figlioli G, Mocci E, Collins I, Chung CC, Hautman C, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Kamineni A, Kolonel LN, Kulke MH, Malats N, Olson SH, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Brais L, Bueno-de-Mesquita HB, Basso D, Berndt SI, Boutron-Ruault MC, Bijlsma MF, Brenner H, Burdette L, Campa D, Caporaso NE, Capurso G, Cavestro GM, Cotterchio M, Costello E, Elena J, Boggi U, Gaziano JM, Gazouli M, Giovannucci EL, Goggins M, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Hu N, Hunter DJ, Iskierka-Jazdzewska E, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, Landi MT, Landi S, Marchand L, Mambrini A, Mannisto S, Milne RL, Neale RE, Oberg AL, Panico S, Patel AV, Peeters PH, Peters U, Pezzilli R, Porta M, Purdue M, Quiros JR, Riboli E, Rothman N, Scarpa A, Scelo G, Shu XO, Silverman DT, Soucek P, Strobel O, Sund M, Małecka-Panas E, Taylor PR, Tavano F, Travis RC, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vashist Y, Vodicka P, Wactawski-Wende J, Wentzensen N, Yu H, Yu K, Zeleniuch-Jacquotte A, Kooperberg C, Risch HA, Jacobs EJ, Li D, Fuchs C, Hoover R, Hartge P, Chanock SJ, Petersen GM, Stolzenberg-Solomon RS, Wolpin BM, Kraft P, Klein AP, Canzian F, Amundadottir LT. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. Oncotarget 2016, 7: 66328-66343. PMID: 27579533, PMCID: PMC5340084, DOI: 10.18632/oncotarget.11041.Peer-Reviewed Original ResearchConceptsPancreatic tissue samplesControl subjectsSingle nucleotide polymorphismsTissue samplesPancreatic Cancer Case-Control ConsortiumCase-control studyPancreatic cancer riskSusceptibility variantsGenome-wide association studiesChromosome 1q32.1Risk lociCancer riskNew susceptibility variantsNR5A2 expressionCancer susceptibility variantsIndependent risk variantsMarked reductionTumorsEuropean descentRisk variantsDisease researchNucleotide polymorphismsCancer risk lociTarget genesSubjects
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 lociCommon variants at the CHEK2 gene locus and risk of epithelial ovarian cancer
Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, Li Q, Marks JR, Berchuck A, Lee JM, Aben KK, Anton-Culver H, Antonenkova N, Bandera E, Bean Y, Beckmann M, Bisogna M, Bjorge L, Bogdanova N, Brinton L, Brooks-Wilson A, Bruinsma F, Butzow R, Campbell I, Carty K, Chang-Claude J, Chenevix-Trench G, Chen A, Chen Z, Cook L, Cramer D, Cunningham J, Cybulski C, Plisiecka-Halasa J, Dennis J, Dicks E, Doherty J, Dörk T, du Bois A, Eccles D, Easton D, Edwards R, Eilber U, Ekici A, Fasching P, Fridley B, Gao Y, Gentry-Maharaj A, Giles G, Glasspool R, Goode E, Goodman M, Gronwald J, Harter P, Hasmad H, Hein A, Heitz F, Hildebrandt M, Hillemanns P, Hogdall E, Hogdall C, Hosono S, Jakubowska A, Paul J, Jensen A, Karlan B, Kjaer S, Kelemen L, Kellar M, Kelley J, Kiemeney L, Krakstad C, Lambrechts D, Lambrechts S, Le N, Lee A, Cannioto R, Leminen A, Lester J, Levine D, Liang D, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger L, Matsuo K, McGuire V, McLaughlin J, Nevanlinna H, McNeish I, Menon U, Modugno F, Moysich K, Narod S, Nedergaard L, Ness R, Azmi M, Odunsi K, Olson S, Orlow I, Orsulic S, Pearce C, Pejovic T, Pelttari L, Permuth-Wey J, Phelan C, Pike M, Poole E, Ramus S, Risch H, Rosen B, Rossing M, Rothstein J, Rudolph A, Runnebaum I, Rzepecka I, Salvesen H, Budzilowska A, Sellers T, Shu X, Shvetsov Y, Siddiqui N, Sieh W, Song H, Southey M, Sucheston L, Tangen I, Teo S, Terry K, Thompson P, Timorek A, Tworoger S, Van Nieuwenhuysen E, Vergote I, Vierkant R, Wang-Gohrke S, Walsh C, Wentzensen N, Whittemore A, Wicklund K, Wilkens L, Woo Y, Wu X, Wu A, Yang H, Zheng W, Ziogas A, Coetzee G, Freedman M, Monteiro A, Moes-Sosnowska J, Kupryjanczyk J, Pharoah P, Gayther S, Schildkraut J. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer. Carcinogenesis 2015, 36: 1341-1353. PMID: 26424751, PMCID: PMC4635670, DOI: 10.1093/carcin/bgv138.Peer-Reviewed Original ResearchConceptsGene locusCommon variantsGenome-wide association studiesAdditional risk variantsDNA repair genesCommon genetic variantsImputation of genotypesCancer Genome Atlas (TCGA) datasetFunctional annotationGenomic regionsTranscription factorsRegulatory elementsNormal fallopian tube tissuesGenome ProjectCausal variantsPrecursor tissueGene expressionSerous epithelial ovarian cancerCandidate SNPsAssociation studiesAdditional genotypingRepair genesSusceptibility genesRisk variantsGenetic variantsCis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer
Lawrenson K, Li Q, Kar S, Seo JH, Tyrer J, Spindler TJ, Lee J, Chen Y, Karst A, Drapkin R, Aben KK, Anton-Culver H, Antonenkova N, Baker H, Bandera E, Bean Y, Beckmann M, Berchuck A, Bisogna M, Bjorge L, Bogdanova N, Brinton L, Brooks-Wilson A, Bruinsma F, Butzow R, Campbell I, Carty K, Chang-Claude J, Chenevix-Trench G, Chen A, Chen Z, Cook L, Cramer D, Cunningham J, Cybulski C, Dansonka-Mieszkowska A, Dennis J, Dicks E, Doherty J, Dörk T, du Bois A, Dürst M, Eccles D, Easton D, Edwards R, Eilber U, Ekici A, Fasching P, Fridley B, Gao Y, Gentry-Maharaj A, Giles G, Glasspool R, Goode E, Goodman M, Grownwald J, Harrington P, Harter P, Hasmad H, Hein A, Heitz F, Hildebrandt M, Hillemanns P, Hogdall E, Hogdall C, Hosono S, Iversen E, Jakubowska A, James P, Jensen A, Ji B, Karlan B, Kruger Kjaer S, Kelemen L, Kellar M, Kelley J, Kiemeney L, Krakstad C, Kupryjanczyk J, Lambrechts D, Lambrechts S, Le N, Lee A, Lele S, Leminen A, Lester J, Levine D, Liang D, Lissowska J, Lu K, Lubinski J, Lundvall L, Massuger L, Matsuo K, McGuire V, McLaughlin J, Nevanlinna H, McNeish I, Menon U, Modugno F, Moysich K, Narod S, Nedergaard L, Ness R, Azmi M, Odunsi K, Olson S, Orlow I, Orsulic S, Weber R, Pearce C, Pejovic T, Pelttari L, Permuth-Wey J, Phelan C, Pike M, Poole E, Ramus S, Risch H, Rosen B, Rossing M, Rothstein J, Rudolph A, Runnebaum I, Rzepecka I, Salvesen H, Schildkraut J, Schwaab I, Sellers T, Shu X, Shvetsov Y, Siddiqui N, Sieh W, Song H, Southey M, Sucheston L, Tangen I, Teo S, Terry K, Thompson P, Timorek A, Tsai Y, Tworoger S, van Altena A, Van Nieuwenhuysen E, Vergote I, Vierkant R, Wang-Gohrke S, Walsh C, Wentzensen N, Whittemore A, Wicklund K, Wilkens L, Woo Y, Wu X, Wu A, Yang H, Zheng W, Ziogas A, Monteiro A, Pharoah P, Gayther S, Freedman M. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer. Nature Communications 2015, 6: 8234. PMID: 26391404, PMCID: PMC4580986, DOI: 10.1038/ncomms9234.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Ovarian EpithelialCell Line, TumorFemaleGene Expression Regulation, NeoplasticGenetic Association StudiesGenetic Predisposition to DiseaseHomeodomain ProteinsHumansNeoplasm ProteinsNeoplasms, Glandular and EpithelialNuchal CordOvarian NeoplasmsProtein BindingQuantitative Trait LociConceptsCandidate susceptibility genesExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisChromosome conformation captureGenome-wide association studiesSusceptibility genesCis-eQTL analysisHigh-grade serous epithelial ovarian cancerAnchorage-independent growthConformation captureHOXD9 promoterTranscriptomic profilingCausal variantsFunctional validationRisk lociLocus analysisAssociation studiesBroader roleFunctional roleGenesContact inhibitionRisk variantsPopulation-doubling timePrecursor cellsHOXD9
2012
Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer
Li D, Duell EJ, Yu K, Risch HA, Olson SH, Kooperberg C, Wolpin BM, Jiao L, Dong X, Wheeler B, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Hartge P, Hoover RN, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Mandelson MT, Petersen G, Zheng W, Agalliu I, Albanes D, Boutron-Ruault MC, Bracci PM, Buring JE, Canzian F, Chang K, Chanock SJ, Cotterchio M, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Bolton J, Hunter DJ, Hutchinson A, Jacobs KB, Jenab M, Khaw KT, Kraft P, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Patel AV, Rabe KG, Riboli E, Shu XO, Tjønneland A, Tobias GS, Trichopoulos D, Virtamo J, Visvanathan K, Watters J, Yu H, Zeleniuch-Jacquotte A, Amundadottir L, Stolzenberg-Solomon RZ. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer. Carcinogenesis 2012, 33: 1384-1390. PMID: 22523087, PMCID: PMC3405651, DOI: 10.1093/carcin/bgs151.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGWAS dataPancreatic developmentSingle nucleotide polymorphismsBiological pathwaysDisease-associated single nucleotide polymorphismsGenome-wide association study dataOriginal genome-wide association studiesGroup of genesPathway-based analysisAssociation study dataSingle-locus methodPathway-based approachDevelopment genesGenetic risk variantsPathway analysisInherited variationSignificant genesAssociation studiesGenesRisk variantsAdaptive rankNominal associationPathwayHNF4G