Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness.

Vivek L PatelEvan L BuschTara M FriebelAngel CroninGoska LeslieLesley McGuffogJulian AdlardSimona AgataBjarni A AgnarssonMunaza AhmedKristiina AittomäkiElisa AlducciIrene L AndrulisAdalgeir ArasonNorbert ArnoldGrazia ArtioliBrita ArverBernd Auber Jacopo AzzolliniJudith BalmañaRosa B BarkardottirDaniel R BarnesAlicia BarrosoDaniel BarrowdaleMuriel BelottiJavier BenitezBirgitte BertelsenMarinus J BlokIstvan BodrogiValérie BonadonaBernardo BonanniDavide BondavalliSusanne E BoonenJulika BordeAke BorgAngela R BradburyAngela BradyCarole BrewerJoan BrunetBruno BuecherSaundra S BuysSantiago Cabezas-CamareroTrinidad CaldésAlmuth CaliebeMaria Adelaide CaligoMariarosaria CalvelloIan G CampbellIleana CarnevaliEstela CarrascoTsun L ChanAnnie T W ChuWendy K ChungKathleen B M ClaesGemo Study CollaboratorsEmbrace CollaboratorsJackie CookLaura CortesiFergus J CouchMary B DalyGiuseppe DamanteEsther DarderRosemarie DavidsonMiguel de la HoyaLara Della PuppaJoe G DennisOrland DíezYuan Chun DingNina DitschSusan M DomchekAlan DonaldsonBernd DworniczakDouglas F EastonDiana M EcclesRosalind A Eeles Hans Ehrencrona Bent EjlertsenChristoph EngelDafydd Gareth EvansLaurence FaivreUlrike FaustLídia FeliubadalóLenka ForetovaFlorentia FostiraGeorge FountzilasDebra FrostVanesa García-BarberánPilar GarreMarion Gauthier-VillarsLajos GécziAndrea GehrigAnne-Marie GerdesPaul GestaGiuseppe GianniniGord GlendonAndrew K GodwinDavid E GoldgarMark H GreeneAngelica M Gutierrez-BarreraEric HahnenUte HamannJan HaukeNatalie HeroldFrans B L HogervorstEllen HonischJohn L HopperPeter J HulickKConFab InvestigatorsHebon InvestigatorsLouise IzattAgnes Jager Paul A JamesRamunas JanaviciusUffe Birk JensenThomas Dyrso JensenOskar Th JohannssonIsabelle Durot Joseph VijaiEunyoung KangKarin KastJohanna I KiiskiSung-Won KimKwang-Pil KoIrene KonstantopoulouGero KramerLotte KroghTorben A KruseAva KwongMirjam LarsenChristine LassetCharlotte LautrupConxi LazaroJihyoun LeeJong Won LeeMin Hyuk LeeJohannes LemkeFabienne LesueurAnnelie LiljegrenAnnika LindblomPatricia LlovetAdria Lopez-FernándezIrene Lopez-PerolioVictor LorcaJennifer T LoudEdmond S K MaPhuong L MaiSiranoush ManoukianVeronique MariLynn MartinLaura MatricardiNoura MebiroukVeronica MediciHanne E J Meijers-HeijboerAlfons MeindlArjen R MensenkampClare MillerDenise Molina GomesMarco MontagnaThea M MooijLidia MoserleEmmanuelle Mouret-FourmeAnna Marie MulliganKatherine L NathansonMarie NavratilovaHeli NevanlinnaDieter NiederacherFinn C Cilius NielsenLiene Nikitina-ZakeKenneth OffitEdith OlahOlufunmilayo I OlopadeKai-Ren OngAna OsorioClaus-Eric OttDomenico Palli Sue-Kyung Park Michael T ParsonsInge Sokilde PedersenBernard PeisselAna PeixotoPedro Pérez-SeguraPaolo Peterlongo Annabeth Høgh PetersenMary E PorteousMiguel Angel PujanaPaolo RadiceJuliane RamserJohanna RantalaMuhammad U RashidKerstin RhiemPiera RizzoloMark E RobsonMatti A RookusCaroline M RossingKathryn J RuddyCatarina SantosClaire SauleRosa ScarpittaRita K SchmutzlerHélène SchusterLeigha SenterCaroline M SeynaevePayal Deepak ShahPriyanka SharmaVivian Y ShinValentina SilvestriJacques SimardChristian F SingerAnne-Bine SkytteKatie SnapeAngela R SolanoPenny SoucyMelissa C Southey Amanda B SpurdleLinda SteeleDoris SteinemannDominique Stoppat-LyonnetAgostina StradellaLone SundeChristian SutterYen Y TanManuel R Teixeira Soo-Hwang TeoMads ThomassenMaria Grazia TibilettiMarc TischkowitzSilvia TognazzoAmanda E TolandStefania TommasiDiana TorresAngela TossAlison H TrainerNadine TungChristi J van AsperenFrederieke H van der BaanLizet E van der KolkRob B van der LuijtLiselotte P van HestLiliana VarescoRaymonda Varon-MateevaAlessandra VielJeroen VierstraeteRoberta VillaAnna von WachenfeldtPhilipp WagnerShan Wang-GohrkeBarbara WappenschmidtJeffrey N WeitzelGreet Wieme Siddhartha YadavDrakoulis YannoukakosSook-Yee YoonCristina ZanzotteraKristin K ZornAnthony V D'AmicoMatthew L FreedmanMark M PomerantzGeorgia Chenevix-TrenchAntonis C AntoniouSusan L NeuhausenLaura OttiniHenriette Roed NielsenTimothy R Rebbeck

Published in: Cancer research (2019)

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

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