Southey, Melissa CGoldgar, David EWinqvist, RobertPylkäs, KatriCouch, FergusTischkowitz, MarcFoulkes, William DDennis, JoeMichailidou, Kyriakivan Rensburg, Elizabeth JHeikkinen, TuomasNevanlinna, HeliHopper, John LDörk, ThiloClaes, Kathleen BMReis-Filho, JorgeTeo, Zhi LingRadice, PaoloCatucci, IrenePeterlongo, PaoloTsimiklis, HelenOdefrey, Fabrice ADowty, James GSchmidt, Marjanka KBroeks, AnnegienHogervorst, Frans BVerhoef, SennoCarpenter, JaneClarke, ChristineScott, Rodney JFasching, Peter AHaeberle, LotharEkici, Arif BBeckmann, Matthias WPeto, Juliandos-Santos-Silva, IsabelFletcher, OliviaJohnson, NicholaBolla, Manjeet KSawyer, Elinor JTomlinson, IanKerin, Michael JMiller, NicolaMarme, FederikBurwinkel, BarbaraYang, RongxiGuénel, PascalTruong, ThérèseMenegaux, FlorenceSanchez, MarieBojesen, StigNielsen, Sune FFlyger, HenrikBenitez, JavierZamora, M PilarArias Perez, Jose IgnacioMenéndez, PrimitivaAnton-Culver, HodaNeuhausen, SusanZiogas, ArgyriosClarke, Christina ABrenner, HermannArndt, VolkerStegmaier, ChristaBrauch, HiltrudBrüning, ThomasKo, Yon-DschunMuranen, Taru AAittomäki, KristiinaBlomqvist, CarlBogdanova, Natalia VAntonenkova, Natalia NLindblom, AnnikaMargolin, SaraMannermaa, ArtoKataja, VesaKosma, Veli-MattiHartikainen, Jaana MSpurdle, Amanda BWauters, ElsSmeets, DominiekBeuselinck, BenoitFloris, GiuseppeChang-Claude, JennyRudolph, AnjaSeibold, PetraFlesch-Janys, DieterOlson, Janet EVachon, CelinePankratz, Vernon SMcLean, CatrionaHaiman, Christopher AHenderson, Brian ESchumacher, FredrickLe Marchand, LoicKristensen, VesselaAlnæs, Grethe GrenakerZheng, WeiHunter, DavidLindstrom, SaraHankinson, SusanKraft, PhillipAndrulis, IreneKnight, Julia AGlendon, GordMulligan, Anna MarieJukkola-Vuorinen, ArjaGrip, MerviKauppila, SailaDevilee, PeterTollenaar, Robert A E MSeynaeve, CarolineHollestelle, AntoinetteGarcia-Closas, MontserratFigueroa, JonineChanock, Stephen JLissowska, JolantaCzene, KamilaDarabi, HatefEriksson, MikaelEccles, Diana MRafiq, SajjadTapper, William JGerty, Sue MHooning, Maartje JMartens, John W MCollée, J MargrietTilanus-Linthorst, MadeleineHall, PerLi, JingmeiBrand, Judith SHumphreys, KeithCox, AngelaReed, Malcolm W RLuccarini, CraigBaynes, CarolineDunning, Alison MHamann, UteTorres, DianaUlmer, Hans UlrichRüdiger, ThomasJakubowska, AnnaLubinski, JanJaworska, KatarzynaDurda, KatarzynaSlager, SusanToland, Amanda EAmbrosone, Christine BYannoukakos, DrakoulisSwerdlow, AnthonyAshworth, AlanOrr, NickJones, MichaelGonzález-Neira, AnnaPita, GuillermoAlonso, M RosarioÁlvarez, NuriaHerrero, DanielTessier, Daniel CVincent, DanielBacot, FrancoisSimard, JacquesDumont, MartineSoucy, PennyEeles, RosalindMuir, KennethWiklund, FredrikGronberg, HenrikSchleutker, JohannaNordestgaard, Børge GWeischer, MarenTravis, Ruth CNeal, DavidDonovan, Jenny LHamdy, Freddie CKhaw, Kay-TeeStanford, Janet LBlot, William JThibodeau, StephenSchaid, Daniel JKelley, Joseph LMaier, ChristianeKibel, AdamCybulski, CezaryCannon-Albright, LisaButterbach, KatjaPark, JongKaneva, RadkaBatra, JyotsnaTeixeira, Manuel RKote-Jarai, ZsofiaAl Olama, Ali AminBenlloch, SaraRenner, Stefan PHartmann, ArndtHein, AlexanderRuebner, MatthiasLambrechts, DietherVan Nieuwenhuysen, ElsVergote, IgnaceLambretchs, SandrinaDoherty, Jennifer ARossing, Mary AnneNickels, StefanEilber, UrsulaWang-Gohrke, ShanOdunsi, KunleSucheston-Campbell, Lara EFriel, GraceLurie, GalinaKilleen, Jeffrey LWilkens, Lynne RGoodman, Marc TRunnebaum, IngoHillemanns, Peter APelttari, Liisa MButzow, RalfModugno, FrancesmaryEdwards, Robert PNess, Roberta BMoysich, Kirsten Bdu Bois, AndreasHeitz, FlorianHarter, PhilippKommoss, StefanKarlan, Beth YWalsh, ChristineLester, JennyJensen, AllanKjaer, Susanne KrügerHøgdall, EstridPeissel, BernardBonanni, BernardoBernard, LorisGoode, Ellen LFridley, Brooke LVierkant, Robert ACunningham, Julie MLarson, Melissa CFogarty, Zachary CKalli, Kimberly RLiang, DongLu, Karen HHildebrandt, Michelle A TWu, XifengLevine, Douglas ADao, FannyBisogna, MariaBerchuck, AndrewIversen, Edwin SMarks, Jeffrey RAkushevich, LucyCramer, DanielSchildkraut, JoellenTerry, KathrynPoole, Elizabeth M.Stampfer, MeirTworoger, ShelleyBandera, Elisa VOrlow, IreneOlson, Sara HBjorge, LineSalvesen, Helga Bvan Altena, Anne MAben, Katja K HKiemeney, Lambertus AMassuger, Leon F A GPejovic, TanjaBean, YukieBrooks-Wilson, AngelaKelemen, Linda ECook, Linda SLe, Nhu DGórski, BohdanGronwald, JacekMenkiszak, JanuszHøgdall, Claus KLundvall, LeneNedergaard, LotteEngelholm, Svend AageDicks, EdTyrer, JonathanCampbell, IanMcNeish, IainPaul, JamesSiddiqui, NadeemGlasspool, RosalindWhittemore, Alice SRothstein, Joseph HMcGuire, ValerieSieh, WeivaCai, HuiShu, Xiao-OuTeten, Rachel TSutphen, RebeccaMcLaughlin, John RNarod, Steven APhelan, Catherine MMonteiro, Alvaro NFenstermacher, DavidLin, Hui-YiPermuth, Jennifer BSellers, Thomas AChen, Y AnnTsai, Ya-YuChen, ZhihuaGentry-Maharaj, AleksandraGayther, Simon ARamus, Susan JMenon, UshaWu, Anna HPearce, Celeste LVan Den Berg, DavidPike, Malcolm CDansonka-Mieszkowska, AgnieszkaPlisiecka-Halasa, JoannaMoes-Sosnowska, JoannaKupryjanczyk, JolantaPharoah, Paul DPSong, HonglinWinship, IngridChenevix-Trench, GeorgiaGiles, Graham GTavtigian, Sean VEaston, Doug FMilne, Roger L2017-01-032016Southey, M. C., D. E. Goldgar, R. Winqvist, K. Pylkäs, F. Couch, M. Tischkowitz, W. D. Foulkes, et al. 2016. “PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.” Journal of medical genetics 53 (12): 800-811. doi:10.1136/jmedgenet-2016-103839. http://dx.doi.org/10.1136/jmedgenet-2016-103839.0022-2593http://nrs.harvard.edu/urn-3:HUL.InstRepos:29739204Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.en-USJournal Article2017-01-0310.1136/jmedgenet-2016-103839