2021
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
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 risk
2020
Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
Barnes DR, Rookus MA, McGuffog L, Leslie G, Mooij TM, Dennis J, Mavaddat N, Adlard J, Ahmed M, Aittomäki K, Andrieu N, Andrulis IL, Arnold N, Arun BK, Azzollini J, Balmaña J, Barkardottir RB, Barrowdale D, Benitez J, Berthet P, Białkowska K, Blanco AM, Blok MJ, Bonanni B, Boonen SE, Borg Å, Bozsik A, Bradbury AR, Brennan P, Brewer C, Brunet J, Buys SS, Caldés T, Caligo MA, Campbell I, Christensen LL, Chung WK, Claes KBM, Colas C, Collonge-Rame M, Cook J, Daly M, Davidson R, de la Hoya M, de Putter R, Delnatte C, Devilee P, Diez O, Ding Y, Domchek S, Dorfling C, Dumont M, Eeles R, Ejlertsen B, Engel C, Evans D, Faivre L, Foretova L, Fostira F, Friedlander M, Friedman E, Frost D, Ganz P, Garber J, Gehrig A, Gerdes A, Gesta P, Giraud S, Glendon G, Godwin A, Goldgar D, González-Neira A, Greene M, Gschwantler-Kaulich D, Hahnen E, Hamann U, Hanson H, Hentschel J, Hogervorst F, Hooning M, Horvath J, Hu C, Hulick P, Imyanitov E, Isaacs C, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, John E, Joseph V, Karlan B, Kast K, Koudijs M, Kruse T, Kwong A, Laitman Y, Lasset C, Lazaro C, Lester J, Lesueur F, Liljegren A, Loud J, Lubiński J, Mai P, Manoukian S, Mari V, Mebirouk N, Meijers-Heijboer H, Meindl A, Mensenkamp A, Miller A, Montagna M, Mouret-Fourme E, Mukherjee S, Mulligan A, Nathanson K, Neuhausen S, Nevanlinna H, Niederacher D, Nielsen F, Nikitina-Zake L, Noguès C, Olah E, Olopade O, Ong K, O’Shaughnessy-Kirwan A, Osorio A, Ott C, Papi L, Park S, Parsons M, Pedersen I, Peissel B, Peixoto A, Peterlongo P, Pfeiler G, Phillips K, Prajzendanc K, Pujana M, Radice P, Ramser J, Ramus S, Rantala J, Rennert G, Risch H, Robson M, Rønlund K, Salani R, Schuster H, Senter L, Shah P, Sharma P, Side L, Singer C, Slavin T, Soucy P, Southey M, Spurdle A, Steinemann D, Steinsnyder Z, Stoppa-Lyonnet D, Sutter C, Tan Y, Teixeira M, Teo S, Thull D, Tischkowitz M, Tognazzo S, Toland A, Trainer A, Tung N, van Engelen K, van Rensburg E, Vega A, Vierstraete J, Wagner G, Walker L, Wang-Gohrke S, Wappenschmidt B, Weitzel J, Yadav S, Yang X, Yannoukakos D, Zimbalatti D, Offit K, Thomassen M, Couch F, Schmutzler R, Simard J, Easton D, Chenevix-Trench G, Antoniou A. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants. Genetics In Medicine 2020, 22: 1653-1666. PMID: 32665703, PMCID: PMC7521995, DOI: 10.1038/s41436-020-0862-x.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerPathogenic variant carriersProspective cohortPolygenic risk scoresVariant carriersCancer riskRisk scoreStrong associationEOC riskHigh-grade serous epithelial ovarian cancerSerous epithelial ovarian cancerER-positive BCBRCA2 pathogenic variantsCarriers of BRCA1Absolute risk differenceEpithelial ovarian cancer riskGeneral population estimatesOvarian cancer riskHR estimatesBRCA2 pathogenic variant carriersBRCA1 carriersBRCA1/2 carriersOvarian cancerBC riskEstrogen receptorGenome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
Zhang H, Ahearn TU, Lecarpentier J, Barnes D, Beesley J, Qi G, Jiang X, O’Mara T, Zhao N, Bolla MK, Dunning AM, Dennis J, Wang Q, Ful ZA, Aittomäki K, Andrulis IL, Anton-Culver H, Arndt V, Aronson KJ, Arun BK, Auer PL, Azzollini J, Barrowdale D, Becher H, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bialkowska K, Blanco A, Blomqvist C, Bogdanova NV, Bojesen SE, Bonanni B, Bondavalli D, Borg A, Brauch H, Brenner H, Briceno I, Broeks A, Brucker SY, Brüning T, Burwinkel B, Buys SS, Byers H, Caldés T, Caligo MA, Calvello M, Campa D, Castelao JE, Chang-Claude J, Chanock SJ, Christiaens M, Christiansen H, Chung WK, Claes KBM, Clarke CL, Cornelissen S, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Diez O, Domchek SM, Dörk T, Dwek M, Eccles DM, Ekici AB, Evans DG, Fasching PA, Figueroa J, Foretova L, Fostira F, Friedman E, Frost D, Gago-Dominguez M, Gapstur SM, Garber J, García-Sáenz JA, Gaudet MM, Gayther SA, Giles GG, Godwin AK, Goldberg MS, Goldgar DE, González-Neira A, Greene MH, Gronwald J, Guénel P, Häberle L, Hahnen E, Haiman CA, Hake CR, Hall P, Hamann U, Harkness EF, Heemskerk-Gerritsen BAM, Hillemanns P, Hogervorst FBL, Holleczek B, Hollestelle A, Hooning MJ, Hoover RN, Hopper JL, Howell A, Huebner H, Hulick PJ, Imyanitov EN, Isaacs C, Izatt L, Jager A, Jakimovska M, Jakubowska A, James P, Janavicius R, Janni W, John E, Jones M, Jung A, Kaaks R, Kapoor P, Karlan B, Keeman R, Khan S, Khusnutdinova E, Kitahara C, Ko Y, Konstantopoulou I, Koppert L, Koutros S, Kristensen V, Laenkholm A, Lambrechts D, Larsson S, Laurent-Puig P, Lazaro C, Lazarova E, Lejbkowicz F, Leslie G, Lesueur F, Lindblom A, Lissowska J, Lo W, Loud J, Lubinski J, Lukomska A, MacInnis R, Mannermaa A, Manoochehri M, Manoukian S, Margolin S, Martinez M, Matricardi L, McGuffog L, McLean C, Mebirouk N, Meindl A, Menon U, Miller A, Mingazheva E, Montagna M, Mulligan A, Mulot C, Muranen T, Nathanson K, Neuhausen S, Nevanlinna H, Neven P, Newman W, Nielsen F, Nikitina-Zake L, Nodora J, Offit K, Olah E, Olopade O, Olsson H, Orr N, Papi L, Papp J, Park-Simon T, Parsons M, Peissel B, Peixoto A, Peshkin B, Peterlongo P, Peto J, Phillips K, Piedmonte M, Plaseska-Karanfilska D, Prajzendanc K, Prentice R, Prokofyeva D, Rack B, Radice P, Ramus S, Rantala J, Rashid M, Rennert G, Rennert H, Risch H, Romero A, Rookus M, Rübner M, Rüdiger T, Saloustros E, Sampson S, Sandler D, Sawyer E, Scheuner M, Schmutzler R, Schneeweiss A, Schoemaker M, Schöttker B, Schürmann P, Senter L, Sharma P, Sherman M, Shu X, Singer C, Smichkoska S, Soucy P, Southey M, Spinelli J, Stone J, Stoppa-Lyonnet D, Swerdlow A, Szabo C, Tamimi R, Tapper W, Taylor J, Teixeira M, Terry M, Thomassen M, Thull D, Tischkowitz M, Toland A, Tollenaar R, Tomlinson I, Torres D, Troester M, Truong T, Tung N, Untch M, Vachon C, van den Ouweland A, van der Kolk L, van Veen E, vanRensburg E, Vega A, Wappenschmidt B, Weinberg C, Weitzel J, Wildiers H, Winqvist R, Wolk A, Yang X, Yannoukakos D, Zheng W, Zorn K, Milne R, Kraft P, Simard J, Pharoah P, Michailidou K, Antoniou A, Schmidt M, Chenevix-Trench G, Easton D, Chatterjee N, García-Closas M. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nature Genetics 2020, 52: 572-581. PMID: 32424353, PMCID: PMC7808397, DOI: 10.1038/s41588-020-0609-2.Peer-Reviewed Original ResearchConceptsSusceptibility lociAssociation studiesGenome-wide association studiesCell-specific enhancerWide association studyNovel breast cancer susceptibility lociNovel susceptibility lociBasal mammary cellsBreast cancer susceptibility lociCancer susceptibility lociTriple-negative diseaseCancer susceptibility variantsChip heritabilityNovel lociPolygenic risk scoresSilico analysisLociSusceptibility variantsGenetic correlationsRisk scoreMammary cellsHuman epidermal growth factor receptor 2 (HER2) statusEpidermal growth factor receptor 2 statusBreast cancer susceptibility variantsEuropean ancestry
2019
Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers
Qian F, Rookus MA, Leslie G, Risch HA, Greene MH, Aalfs CM, Adank MA, Adlard J, Agnarsson BA, Ahmed M, Aittomäki K, Andrulis IL, Arnold N, Arun BK, Ausems MGEM, Azzollini J, Barrowdale D, Barwell J, Benitez J, Białkowska K, Bonadona V, Borde J, Borg A, Bradbury AR, Brunet J, Buys SS, Caldés T, Caligo MA, Campbell I, Carter J, Chiquette J, Chung WK, Claes KBM, Collée JM, Collonge-Rame MA, Couch FJ, Daly MB, Delnatte C, Diez O, Domchek SM, Dorfling CM, Eason J, Easton DF, Eeles R, Engel C, Evans DG, Faivre L, Feliubadaló L, Foretova L, Friedman E, Frost D, Ganz PA, Garber J, Garcia-Barberan V, Gehrig A, Glendon G, Godwin AK, Gómez Garcia EB, Hamann U, Hauke J, Hopper JL, Hulick PJ, Imyanitov EN, Isaacs C, Izatt L, Jakubowska A, Janavicius R, John EM, Karlan BY, Kets CM, Laitman Y, Lázaro C, Leroux D, Lester J, Lesueur F, Loud JT, Lubiński J, Łukomska A, McGuffog L, Mebirouk N, Meijers-Heijboer HEJ, Meindl A, Miller A, Montagna M, Mooij TM, Mouret-Fourme E, Nathanson KL, Nehoray B, Neuhausen SL, Nevanlinna H, Nielsen FC, Offit K, Olah E, Ong KR, Oosterwijk JC, Ottini L, Parsons MT, Peterlongo P, Pfeiler G, Pradhan N, Radice P, Ramus SJ, Rantala J, Rennert G, Robson M, Rodriguez GC, Salani R, Scheuner MT, Schmutzler RK, Shah PD, Side LE, Simard J, Singer CF, Steinemann D, Stoppa-Lyonnet D, Tan YY, Teixeira MR, Terry MB, Thomassen M, Tischkowitz M, Tognazzo S, Toland AE, Tung N, van Asperen CJ, van Engelen K, van Rensburg EJ, Venat-Bouvet L, Vierstraete J, Wagner G, Walker L, Weitzel JN, Yannoukakos D, Antoniou A, Goldgar D, Olopade O, Chenevix-Trench G, Rebbeck T, Huo D. Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. British Journal Of Cancer 2019, 121: 180-192. PMID: 31213659, PMCID: PMC6738050, DOI: 10.1038/s41416-019-0492-8.Peer-Reviewed Original ResearchConceptsBody mass indexOvarian cancer riskBRCA1/2 mutation carriersBRCA2 mutation carriersCancer riskMutation carriersMass indexGeneral populationHigher ovarian cancer riskHigher body mass indexGenetic scoreOvarian cancer casesMendelian randomisation studyMendelian randomisation approachConsortium of InvestigatorsPostmenopausal womenPremenopausal womenMenopausal statusCancer casesCox modelConclusionOur observationsRandomisation approachM2 increaseRiskPositive association
2017
Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer
Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, Dennis J, Pirie A, Riggan MJ, Chornokur G, Earp MA, Lyra PC, Lee JM, Coetzee S, Beesley J, McGuffog L, Soucy P, Dicks E, Lee A, Barrowdale D, Lecarpentier J, Leslie G, Aalfs CM, Aben KKH, Adams M, Adlard J, Andrulis IL, Anton-Culver H, Antonenkova N, Aravantinos G, Arnold N, Arun B, Arver B, Azzollini J, Balmaña J, Banerjee S, Barjhoux L, Barkardottir R, Bean Y, Beckmann M, Beeghly-Fadiel A, Benitez J, Bermisheva M, Bernardini M, Birrer M, Bjorge L, Black A, Blankstein K, Blok M, Bodelon C, Bogdanova N, Bojesen A, Bonanni B, Borg Å, Bradbury A, Brenton J, Brewer C, Brinton L, Broberg P, Brooks-Wilson A, Bruinsma F, Brunet J, Buecher B, Butzow R, Buys S, Caldes T, Caligo M, Campbell I, Cannioto R, Carney M, Cescon T, Chan S, Chang-Claude J, Chanock S, Chen X, Chiew Y, Chiquette J, Chung W, Claes K, Conner T, Cook L, Cook J, Cramer D, Cunningham J, D'Aloisio A, Daly M, Damiola F, Damirovna S, Dansonka-Mieszkowska A, Dao F, Davidson R, DeFazio A, Delnatte C, Doheny K, Diez O, Ding Y, Doherty J, Domchek S, Dorfling C, Dörk T, Dossus L, Duran M, Dürst M, Dworniczak B, Eccles D, Edwards T, Eeles R, Eilber U, Ejlertsen B, Ekici A, Ellis S, Elvira M, Eng K, Engel C, Evans D, Fasching P, Ferguson S, Ferrer S, Flanagan J, Fogarty Z, Fortner R, Fostira F, Foulkes W, Fountzilas G, Fridley B, Friebel T, Friedman E, Frost D, Ganz P, Garber J, García M, Garcia-Barberan V, Gehrig A, Gentry-Maharaj A, Gerdes A, Giles G, Glasspool R, Glendon G, Godwin A, Goldgar D, Goranova T, Gore M, Greene M, Gronwald J, Gruber S, Hahnen E, Haiman C, Håkansson N, Hamann U, Hansen T, Harrington P, Harris H, Hauke J, Hein A, Henderson A, Hildebrandt M, Hillemanns P, Hodgson S, Høgdall C, Høgdall E, Hogervorst F, Holland H, Hooning M, Hosking K, Huang R, Hulick P, Hung J, Hunter D, Huntsman D, Huzarski T, Imyanitov E, Isaacs C, Iversen E, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, Jernetz M, Jensen A, Jensen U, John E, Johnatty S, Jones M, Kannisto P, Karlan B, Karnezis A, Kast K, Kennedy C, Khusnutdinova E, Kiemeney L, Kiiski J, Kim S, Kjaer S, Köbel M, Kopperud R, Kruse T, Kupryjanczyk J, Kwong A, Laitman Y, Lambrechts D, Larrañaga N, Larson M, Lazaro C, Le N, Le Marchand L, Lee J, Lele S, Leminen A, Leroux D, Lester J, Lesueur F, Levine D, Liang D, Liebrich C, Lilyquist J, Lipworth L, Lissowska J, Lu K, Lubinński J, Luccarini C, Lundvall L, Mai P, Mendoza-Fandiño G, Manoukian S, Massuger L, May T, Mazoyer S, McAlpine J, McGuire V, McLaughlin J, McNeish I, Meijers-Heijboer H, Meindl A, Menon U, Mensenkamp A, Merritt M, Milne R, Mitchell G, Modugno F, Moes-Sosnowska J, Moffitt M, Montagna M, Moysich K, Mulligan A, Musinsky J, Nathanson K, Nedergaard L, Ness R, Neuhausen S, Nevanlinna H, Niederacher D, Nussbaum R, Odunsi K, Olah E, Olopade O, Olsson H, Olswold C, O'Malley D, Ong K, Onland-Moret N, Orr N, Orsulic S, Osorio A, Palli D, Papi L, Park-Simon T, Paul J, Pearce C, Pedersen I, Peeters P, Peissel B, Peixoto A, Pejovic T, Pelttari L, Permuth J, Peterlongo P, Pezzani L, Pfeiler G, Phillips K, Piedmonte M, Pike M, Piskorz A, Poblete S, Pocza T, Poole E, Poppe B, Porteous M, Prieur F, Prokofyeva D, Pugh E, Pujana M, Pujol P, Radice P, Rantala J, Rappaport-Fuerhauser C, Rennert G, Rhiem K, Rice P, Richardson A, Robson M, Rodriguez G, Rodríguez-Antona C, Romm J, Rookus M, Rossing M, Rothstein J, Rudolph A, Runnebaum I, Salvesen H, Sandler D, Schoemaker M, Senter L, Setiawan V, Severi G, Sharma P, Shelford T, Siddiqui N, Side L, Sieh W, Singer C, Sobol H, Song H, Southey M, Spurdle A, Stadler Z, Steinemann D, Stoppa-Lyonnet D, Sucheston-Campbell L, Sukiennicki G, Sutphen R, Sutter C, Swerdlow A, Szabo C, Szafron L, Tan Y, Taylor J, Tea M, Teixeira M, Teo S, Terry K, Thompson P, Thomsen L, Thull D, Tihomirova L, Tinker A, Tischkowitz M, Tognazzo S, Toland A, Tone A, Trabert B, Travis R, Trichopoulou A, Tung N, Tworoger S, van Altena A, Van Den Berg D, van der Hout A, van der Luijt R, Van Heetvelde M, Van Nieuwenhuysen E, van Rensburg E, Vanderstichele A, Varon-Mateeva R, Vega A, Edwards D, Vergote I, Vierkant R, Vijai J, Vratimos A, Walker L, Walsh C, Wand D, Wang-Gohrke S, Wappenschmidt B, Webb P, Weinberg C, Weitzel J, Wentzensen N, Whittemore A, Wijnen J, Wilkens L, Wolk A, Woo M, Wu X, Wu A, Yang H, Yannoukakos D, Ziogas A, Zorn K, Narod S, Easton D, Amos C, Schildkraut J, Ramus S, Ottini L, Goodman M, Park S, Kelemen L, Risch H, Thomassen M, Offit K, Simard J, Schmutzler R, Hazelett D, Monteiro A, Couch F, Berchuck A, Chenevix-Trench G, Goode E, Sellers T, Gayther S, Antoniou A, Pharoah P. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nature Genetics 2017, 49: 680-691. PMID: 28346442, PMCID: PMC5612337, DOI: 10.1038/ng.3826.Peer-Reviewed Original ResearchMeSH KeywordsAllelesBRCA1 ProteinBRCA2 ProteinCarcinoma, Ovarian EpithelialFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMeta-Analysis as TopicMutationNeoplasms, Glandular and EpithelialOvarian NeoplasmsPolymorphism, Single NucleotideRisk FactorsTelomere-Binding ProteinsConceptsNew susceptibility lociSusceptibility lociGenome-wide association studiesLarge genome-wide association studiesCandidate susceptibility genesRegulatory featuresAssociation studiesSusceptibility genesLociIntegrated analysisEpithelial ovarian cancer histotypesGenesOvarian cancer histotypesOvarian cancerCancer histotypesOBFC1Different histotypesEpithelial ovarian cancerIdentificationRisk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted?
McGee J, Giannakeas V, Karlan B, Lubinski J, Gronwald J, Rosen B, McLaughlin J, Risch H, Sun P, Foulkes WD, Neuhausen SL, Kotsopoulos J, Narod SA, Group O. Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted? Gynecologic Oncology 2017, 145: 346-351. PMID: 28314588, DOI: 10.1016/j.ygyno.2017.02.032.Peer-Reviewed Original ResearchConceptsBRCA mutation carriersOvarian cancer patientsOvarian cancerBreast cancerMutation carriersPreventive mastectomyCancer patientsActuarial riskStage III/IV ovarian cancerUnaffected BRCA mutation carriersEarly-stage ovarian cancerBreast cancer incidenceStage ovarian cancerMutation-carrying patientsProportional hazards modelCause of mortalityImpact of mastectomyOvarian cancer diagnosisProbability of deathBreast surveillanceCause mortalityAnnual mortality rateClinical benefitBreast surgeryInternational registry
2016
Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study
Childs EJ, Chaffee KG, Gallinger S, Syngal S, Schwartz AG, Cote ML, Bondy ML, Hruban RH, Chanock SJ, Hoover RN, Fuchs CS, Rider DN, Amundadottir LT, Stolzenberg-Solomon R, Wolpin BM, Risch HA, Goggins MG, Petersen GM, Klein AP. Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. Cancer Epidemiology Biomarkers & Prevention 2016, 25: 1185-1191. PMID: 27197284, PMCID: PMC5321211, DOI: 10.1158/1055-9965.epi-15-1217.Peer-Reviewed Original ResearchConceptsHigh-risk populationPancreatic cancerEarly onset pancreatic cancerPancreatic cancer familiesHigh-risk patientsMagnitude of associationHigh-penetrance genesGenetic variantsPancreatic cancer susceptibilityUnselected patientsFamily historyProstate cancerColon cancerCommon genetic variantsCancerCancer familiesLogistic regressionCancer susceptibilityCancer susceptibility lociPatientsCancer lociOvarianCommon variantsBreastRisk
2015
Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status
Kotsopoulos J, Rosen B, Fan I, Moody J, McLaughlin JR, Risch H, May T, Sun P, Narod SA. Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status. Gynecologic Oncology 2015, 140: 42-47. PMID: 26556769, DOI: 10.1016/j.ygyno.2015.11.009.Peer-Reviewed Original ResearchConceptsBRCA mutation statusLong-term survivalEpithelial ovarian cancerResidual diseaseOvarian cancerMutation carriersMutation statusOntario Cancer RegistryTreatment-related factorsTen-year survivalBRCA2 mutation carriersBRCA1 mutation carriersMajority of womenInitial survival advantageActuarial survivalMortality benefitSerous cancerCancer RegistryBRCA carriersBRCA mutationsMedical recordsBRCA2 mutationsSurvival statusSurvival advantageClinical informationTERT gene harbors multiple variants associated with pancreatic cancer susceptibility
Campa D, Rizzato C, Stolzenberg-Solomon R, Pacetti P, Vodicka P, Cleary SP, Capurso G, Bueno-de-Mesquita HB, Werner J, Gazouli M, Butterbach K, Ivanauskas A, Giese N, Petersen GM, Fogar P, Wang Z, Bassi C, Ryska M, Theodoropoulos GE, Kooperberg C, Li D, Greenhalf W, Pasquali C, Hackert T, Fuchs CS, Mohelnikova-Duchonova B, Sperti C, Funel N, Dieffenbach AK, Wareham NJ, Buring J, Holcátová I, Costello E, Zambon CF, Kupcinskas J, Risch HA, Kraft P, Bracci PM, Pezzilli R, Olson SH, Sesso HD, Hartge P, Strobel O, Małecka-Panas E, Visvanathan K, Arslan AA, Pedrazzoli S, Souček P, Gioffreda D, Key TJ, Talar-Wojnarowska R, Scarpa A, Mambrini A, Jacobs EJ, Jamroziak K, Klein A, Tavano F, Bambi F, Landi S, Austin MA, Vodickova L, Brenner H, Chanock SJ, Delle Fave G, Piepoli A, Cantore M, Zheng W, Wolpin BM, Amundadottir LT, Canzian F. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. International Journal Of Cancer 2015, 137: 2175-2183. PMID: 25940397, PMCID: PMC4548797, DOI: 10.1002/ijc.29590.Peer-Reviewed Original ResearchConceptsPancreatic cancer riskCancer riskTelomerase reverse transcriptasePancreatic cancerSingle nucleotide polymorphismsAdditional single nucleotide polymorphismsTelomerase RNA component genePancreatic cancer susceptibilitySignificant associationCommon susceptibility lociCancer susceptibilityStatistical significanceRs401681RiskReverse transcriptaseTERT locusCancerDisease researchMultiple testingNucleotide polymorphismsLinkage disequilibriumIndependent variantsSusceptibility lociIdentification of six new susceptibility loci for invasive epithelial ovarian cancer
Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, Lawrenson K, McGuffog L, Healey S, Lee JM, Spindler TJ, Lin YG, Pejovic T, Bean Y, Li Q, Coetzee S, Hazelett D, Miron A, Southey M, Terry MB, Goldgar DE, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Neuhausen SL, Ding YC, Hansen TV, Jønson L, Gerdes AM, Ejlertsen B, Barrowdale D, Dennis J, Benitez J, Osorio A, Garcia MJ, Komenaka I, Weitzel JN, Ganschow P, Peterlongo P, Bernard L, Viel A, Bonanni B, Peissel B, Manoukian S, Radice P, Papi L, Ottini L, Fostira F, Konstantopoulou I, Garber J, Frost D, Perkins J, Platte R, Ellis S, Godwin A, Schmutzler R, Meindl A, Engel C, Sutter C, Sinilnikova O, Damiola F, Mazoyer S, Stoppa-Lyonnet D, Claes K, De Leeneer K, Kirk J, Rodriguez G, Piedmonte M, O'Malley D, de la Hoya M, Caldes T, Aittomäki K, Nevanlinna H, Collée J, Rookus M, Oosterwijk J, Tihomirova L, Tung N, Hamann U, Isaccs C, Tischkowitz M, Imyanitov E, Caligo M, Campbell I, Hogervorst F, Olah E, Diez O, Blanco I, Brunet J, Lazaro C, Pujana M, Jakubowska A, Gronwald J, Lubinski J, Sukiennicki G, Barkardottir R, Plante M, Simard J, Soucy P, Montagna M, Tognazzo S, Teixeira M, Pankratz V, Wang X, Lindor N, Szabo C, Kauff N, Vijai J, Aghajanian C, Pfeiler G, Berger A, Singer C, Tea M, Phelan C, Greene M, Mai P, Rennert G, Mulligan A, Tchatchou S, Andrulis I, Glendon G, Toland A, Jensen U, Kruse T, Thomassen M, Bojesen A, Zidan J, Friedman E, Laitman Y, Soller M, Liljegren A, Arver B, Einbeigi Z, Stenmark-Askmalm M, Olopade O, Nussbaum R, Rebbeck T, Nathanson K, Domchek S, Lu K, Karlan B, Walsh C, Lester J, Hein A, Ekici A, Beckmann M, Fasching P, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Lambrechts S, Dicks E, Doherty J, Wicklund K, Rossing M, Rudolph A, Chang-Claude J, Wang-Gohrke S, Eilber U, Moysich K, Odunsi K, Sucheston L, Lele S, Wilkens L, Goodman M, Thompson P, Shvetsov Y, Runnebaum I, Dürst M, Hillemanns P, Dörk T, Antonenkova N, Bogdanova N, Leminen A, Pelttari L, Butzow R, Modugno F, Kelley J, Edwards R, Ness R, du Bois A, Heitz F, Schwaab I, Harter P, Matsuo K, Hosono S, Orsulic S, Jensen A, Kjaer S, Hogdall E, Hasmad H, Azmi M, Teo S, Woo Y, Fridley B, Goode E, Cunningham J, Vierkant R, Bruinsma F, Giles G, Liang D, Hildebrandt M, Wu X, Levine D, Bisogna M, Berchuck A, Iversen E, Schildkraut J, Concannon P, Weber R, Cramer D, Terry K, Poole E, Tworoger S, Bandera E, Orlow I, Olson S, Krakstad C, Salvesen H, Tangen I, Bjorge L, van Altena A, Aben K, Kiemeney L, Massuger L, Kellar M, Brooks-Wilson A, Kelemen L, Cook L, Le N, Cybulski C, Yang H, Lissowska J, Brinton L, Wentzensen N, Hogdall C, Lundvall L, Nedergaard L, Baker H, Song H, Eccles D, McNeish I, Paul J, Carty K, Siddiqui N, Glasspool R, Whittemore A, Rothstein J, McGuire V, Sieh W, Ji B, Zheng W, Shu X, Gao Y, Rosen B, Risch H, McLaughlin J, Narod S, Monteiro A, Chen A, Lin H, Permuth-Wey J, Sellers T, Tsai Y, Chen Z, Ziogas A, Anton-Culver H, Gentry-Maharaj A, Menon U, Harrington P, Lee A, Wu A, Pearce C, Coetzee G, Pike M, Dansonka-Mieszkowska A, Timorek A, Rzepecka I, Kupryjanczyk J, Freedman M, Noushmehr H, Easton D, Offit K, Couch F, Gayther S, Pharoah P, Antoniou A, Chenevix-Trench G. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics 2015, 47: 164-171. PMID: 25581431, PMCID: PMC4445140, DOI: 10.1038/ng.3185.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAllelesBRCA1 ProteinBRCA2 ProteinCarcinoma, Ovarian EpithelialFemaleGenes, ReporterGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHeterozygoteHumansMutationNeoplasms, Glandular and EpithelialOvarian NeoplasmsPolymorphism, Single NucleotideQuantitative Trait LociRiskYoung Adult
2014
Risk Factors for Ovarian Cancers With and Without Microsatellite Instability
Segev Y, Pal T, Rosen B, McLaughlin JR, Sellers TA, Risch HA, Zhang S, Sun P, Narod SA, Schildkraut J. Risk Factors for Ovarian Cancers With and Without Microsatellite Instability. International Journal Of Gynecological Cancer 2014, 24: 664-669. PMID: 24755492, DOI: 10.1097/igc.0000000000000134.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Clear CellAdenocarcinoma, MucinousBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsCanadaCystadenocarcinoma, SerousDNA, NeoplasmEndometrial NeoplasmsFemaleGenetic Predisposition to DiseaseHumansMicrosatellite InstabilityMicrosatellite RepeatsMiddle AgedMutationNeoplasm StagingOvarian NeoplasmsPrognosisRisk FactorsSyndromeUnited StatesConceptsOvarian cancer patientsOral contraceptive useBody mass indexEpithelial ovarian cancerOvarian cancerCancer patientsHistologic subtypeMass indexTubal ligationRisk factorsBRCA2 mutationsContraceptive usePast oral contraceptive usePrimary epithelial ovarian cancerOvarian cancer risk factorsBRCA1 mutationsNational Cancer Institute criteriaProtective factorsSpecific histologic subtypesCancer risk factorsPopulation-based studyMSI-high cancersCases of cancerMSI-high tumorsBRCA2 mutation status
2013
Preventing ovarian cancer through genetic testing: a population‐based study
Finch A, Bacopulos S, Rosen B, Fan I, Bradley L, Risch H, McLaughlin JR, Lerner‐Ellis J, Narod SA. Preventing ovarian cancer through genetic testing: a population‐based study. Clinical Genetics 2013, 86: 496-499. PMID: 24199689, DOI: 10.1111/cge.12313.Peer-Reviewed Original ResearchConceptsOvarian cancerGenetic testingGenetic testing criteriaInvasive ovarian cancerPopulation-based studyOvarian cancer patientsBRCA2 gene mutationsGenetic test resultsDevelopment of cancerCancer patientsBRCA2 mutationsMutation carriersUnselected casesEligibility criteriaCancerPatientsGene mutationsProvince of OntarioWomenPotential utilityPopulation levelBRCA1MutationsPPM1D Mutations in Circulating White Blood Cells and the Risk for Ovarian Cancer
Akbari MR, Lepage P, Rosen B, McLaughlin J, Risch H, Minden M, Narod SA. PPM1D Mutations in Circulating White Blood Cells and the Risk for Ovarian Cancer. Journal Of The National Cancer Institute 2013, 106: djt323. PMID: 24262437, DOI: 10.1093/jnci/djt323.Peer-Reviewed Original ResearchMeSH KeywordsAgedBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsCanadaCase-Control StudiesFemaleGenetic Predisposition to DiseaseHeterozygoteHumansIncidenceLeukocytesMiddle AgedMutationOdds RatioOvarian NeoplasmsPhosphoprotein PhosphatasesProportional Hazards ModelsProtein Phosphatase 2CRisk AssessmentRisk FactorsConceptsCase patientsWhite blood cellsOvarian cancerControl subjectsOvarian cancer case patientsFemale first-degree relativesBlood cellsCancer case patientsFirst-degree relativesLifetime riskBreast cancerFamily historyMutation carriersPatientsCancerPast historyTruncating mutationsBreastRiskMutationsSubjectsCellsNoncarriersMortalityWomenLong-Term Ovarian Cancer Survival Associated With Mutation in BRCA1 or BRCA2
McLaughlin JR, Rosen B, Moody J, Pal T, Fan I, Shaw PA, Risch HA, Sellers TA, Sun P, Narod SA. Long-Term Ovarian Cancer Survival Associated With Mutation in BRCA1 or BRCA2. Journal Of The National Cancer Institute 2013, 105: 141-148. PMID: 23257159, PMCID: PMC3611851, DOI: 10.1093/jnci/djs494.Peer-Reviewed Original ResearchConceptsInvasive ovarian cancerOvarian cancerBRCA2 mutationsLong-term survival benefitOvarian cancer-specific survivalCancer-specific survivalOvarian cancer survivalSerous ovarian cancerShort-term survival advantageBRCA1 mutation carriersLong-term survivalHazard ratioSurvival benefitBetter prognosisUnselected womenBRCA2 carriersCancer survivalMutation carriersSurvival advantageSurvival analysisCancerDiagnosisTime pointsWomenSurvival
2012
Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer
Pal T, Akbari MR, Sun P, Lee JH, Fulp J, Thompson Z, Coppola D, Nicosia S, Sellers TA, McLaughlin J, Risch HA, Rosen B, Shaw P, Schildkraut J, Narod SA. Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. British Journal Of Cancer 2012, 107: 1783-1790. PMID: 23047549, PMCID: PMC3493867, DOI: 10.1038/bjc.2012.452.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCarcinoma, Ovarian EpithelialColorectal NeoplasmsColorectal Neoplasms, Hereditary NonpolyposisDNA Mismatch RepairDNA-Binding ProteinsFemaleHumansMiddle AgedMutationMutL Protein Homolog 1MutS Homolog 2 ProteinNeoplasms, Glandular and EpithelialNuclear ProteinsOvarian NeoplasmsConceptsHereditary non-polyposis colorectal cancerPopulation-based studyEpithelial ovarian cancerOvarian cancerNon-polyposis colorectal cancerNon-serous histologyPathogenic mutation carriersMismatch repair gene mutationsGene mutationsOvarian cancer patientsHNPCC genesPopulation-based sampleRepair gene mutationsMismatch repair genesFamily history informationPathogenic missense variantsColorectal cancerMean ageCancer patientsMSH6 mutationsTreatment decisionsMutation carriersFrequency of mutationsPathogenic variantsCancer
2011
Clinical impact of unclassified variants of the BRCA1 and BRCA2 genes
Akbari MR, Zhang S, Fan I, Royer R, Li S, Risch H, McLaughlin J, Rosen B, Sun P, Narod SA. Clinical impact of unclassified variants of the BRCA1 and BRCA2 genes. Journal Of Medical Genetics 2011, 48: 783. PMID: 21965345, DOI: 10.1136/jmedgenet-2011-100305.Peer-Reviewed Original ResearchConceptsFirst-degree relativesFemale first-degree relativesRelatives of patientsOvarian cancerCumulative riskPathogenic mutationsUnclassified variantsRisk of cancerHistorical cohortBRCA2 mutationsClinical impactHigh riskBRCA2 genesCancerUnknown significancePatientsMissense variantsFunctional effectsWomenRiskBRCA1PenetranceMutationsRelativesCohort
2007
Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study
McLaughlin JR, Risch HA, Lubinski J, Moller P, Ghadirian P, Lynch H, Karlan B, Fishman D, Rosen B, Neuhausen SL, Offit K, Kauff N, Domchek S, Tung N, Friedman E, Foulkes W, Sun P, Narod SA, Group O. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. The Lancet Oncology 2007, 8: 26-34. PMID: 17196508, DOI: 10.1016/s1470-2045(06)70983-4.Peer-Reviewed Original ResearchConceptsInvasive ovarian cancerCarriers of BRCA1Case-control studyOral contraceptivesOvarian cancerBRCA2 mutationsTubal ligationRisk factorsBRCA1 mutationsReproductive risk factorsPopulation-based studyOvarian cancer riskPossible adverse effectsYear of birthInternational registryMenstrual cycleOdds ratioBreast cancerMutation carriersReproductive historyContraceptivesBRCA2 genesCancerAdverse effectsWomen
2006
Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin–Cohort Study in Ontario, Canada
Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, Tang J, Li S, Zhang S, Shaw PA, Narod SA. Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin–Cohort Study in Ontario, Canada. Journal Of The National Cancer Institute 2006, 98: 1694-1706. PMID: 17148771, DOI: 10.1093/jnci/djj465.Peer-Reviewed Original ResearchConceptsIncident ovarian cancerAge 80 yearsGeneral Ontario populationOvarian cancerBRCA2 mutationsTypes of cancerMutation carriageCumulative incidenceRelative riskBreast cancerHigh riskGeneral populationBRCA1 mutationsInvasive ovarian cancerCancer incidence ratesFirst-degree relativesBRCA2 mutation frequencyOntario populationUnselected patientsMale breastTestis cancerCancer outcomesPancreatic cancerIncidence rateCancer risk
2003
Reproductive factors and ovarian cancer risk in Jewish BRCA1 and BRCA2 mutation carriers (United States)
Modugno F, Moslehi R, Ness RB, Nelson DB, Belle S, Kant JA, Wheeler JE, Wonderlick A, Fishman D, Karlan B, Risch H, Cramer DW, Dube MP, Narod SA. Reproductive factors and ovarian cancer risk in Jewish BRCA1 and BRCA2 mutation carriers (United States). Cancer Causes & Control 2003, 14: 439-446. PMID: 12946038, DOI: 10.1023/a:1024932427503.Peer-Reviewed Original ResearchConceptsBRCA1 carriersOC useTubal ligationOvarian cancerReproductive factorsInvasive epithelial ovarian cancerFounder mutationOral contraceptive useHistory of breastfeedingEpithelial ovarian cancerOvarian cancer casesOvarian cancer riskBRCA1 founder mutationsBRCA2 mutation carriersAshkenazi founder mutationsCase-only studyNulliparous womenGynecologic surgeryBRCA1/2 carriersRisk factorsBRCA2 mutationsCancer casesLive birthsBRCA1/2 mutationsContraceptive useRe: Cancer Risks in BRCA1 Carriers: Time for the Next Generation of Studies
Risch HA, Narod SA. Re: Cancer Risks in BRCA1 Carriers: Time for the Next Generation of Studies. Journal Of The National Cancer Institute 2003, 95: 758-758. PMID: 12759395, DOI: 10.1093/jnci/95.10.758.Peer-Reviewed Original Research