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- PMID: 22253144
- UKPMCID: 22253144
- DOI: 10.1002/humu.22025
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Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.
Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; ; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E; Aalfs, Cora M; Meijers-Heijboer, Hanne E J; van Asperen, Christi J; van Roozendaal, K E P; Hoogerbrugge, Nicoline; Collée, J Margriet; Kriege, Mieke; van der Luijt, Rob B; ; ; Peock, Susan; Frost, Debra; Ellis, Steve D; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J; Walker, Lisa; Porteous, Mary E; Kennedy, M John; Pathak, Harsh; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; ; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B; Karlan, Beth Y; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A; Beattie, Mary S; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B; ; Neuhausen, Susan L; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H; Mai, Phuong L; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; ; Pharoah, Paul D P; Gayther, Simon A; Simard, Jacques; Easton, Douglas F; Couch, Fergus J; Chenevix-Trench, Georgia;
Human mutation. 2012;33(4):690-702.
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Full-text held externally
- PMID: 22253144
- UKPMCID: 22253144
- DOI: 10.1002/humu.22025
Abstract
Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.
Bibliographic metadata
- Ramus, Susan J
- Antoniou, Antonis C
- Kuchenbaecker, Karoline B
- Soucy, Penny
- Beesley, Jonathan
- Chen, Xiaoqing
- McGuffog, Lesley
- Sinilnikova, Olga M
- Healey, Sue
- Barrowdale, Daniel
- Lee, Andrew
- Thomassen, Mads
- Gerdes, Anne-Marie
- Kruse, Torben A
- Jensen, Uffe Birk
- Skytte, Anne-Bine
- Caligo, Maria A
- Liljegren, Annelie
- Lindblom, Annika
- Olsson, HÃ¥kan
- Kristoffersson, Ulf
- Stenmark-Askmalm, Marie
- Melin, Beatrice
- Domchek, Susan M
- Nathanson, Katherine L
- Rebbeck, Timothy R
- Jakubowska, Anna
- Lubinski, Jan
- Jaworska, Katarzyna
- Durda, Katarzyna
- Złowocka, Elżbieta
- Gronwald, Jacek
- Huzarski, Tomasz
- Byrski, Tomasz
- Cybulski, Cezary
- Toloczko-Grabarek, Aleksandra
- Osorio, Ana
- Benitez, Javier
- Duran, Mercedes
- Tejada, Maria-Isabel
- Hamann, Ute
- Rookus, Matti
- van Leeuwen, Flora E
- Aalfs, Cora M
- Meijers-Heijboer, Hanne E J
- van Asperen, Christi J
- van Roozendaal, K E P
- Hoogerbrugge, Nicoline
- Collée, J Margriet
- Kriege, Mieke
- van der Luijt, Rob B
- Peock, Susan
- Frost, Debra
- Ellis, Steve D
- Platte, Radka
- Fineberg, Elena
- Evans, D Gareth
- Lalloo, Fiona
- Jacobs, Chris
- Eeles, Ros
- Adlard, Julian
- Davidson, Rosemarie
- Eccles, Diana
- Cole, Trevor
- Cook, Jackie
- Paterson, Joan
- Douglas, Fiona
- Brewer, Carole
- Hodgson, Shirley
- Morrison, Patrick J
- Walker, Lisa
- Porteous, Mary E
- Kennedy, M John
- Pathak, Harsh
- Godwin, Andrew K
- Stoppa-Lyonnet, Dominique
- Caux-Moncoutier, Virginie
- de Pauw, Antoine
- Gauthier-Villars, Marion
- Mazoyer, Sylvie
- Léoné, Mélanie
- Calender, Alain
- Lasset, Christine
- Bonadona, Valérie
- Hardouin, Agnès
- Berthet, Pascaline
- Bignon, Yves-Jean
- Uhrhammer, Nancy
- Faivre, Laurence
- Loustalot, Catherine
- Buys, Saundra
- Daly, Mary
- Miron, Alex
- Terry, Mary Beth
- Chung, Wendy K
- John, Esther M
- Southey, Melissa
- Goldgar, David
- Singer, Christian F
- Tea, Muy-Kheng
- Pfeiler, Georg
- Fink-Retter, Anneliese
- Hansen, Thomas v O
- Ejlertsen, Bent
- Johannsson, Oskar Th
- Offit, Kenneth
- Kirchhoff, Tomas
- Gaudet, Mia M
- Vijai, Joseph
- Robson, Mark
- Piedmonte, Marion
- Phillips, Kelly-Anne
- Van Le, Linda
- Hoffman, James S
- Ewart Toland, Amanda
- Montagna, Marco
- Tognazzo, Silvia
- Imyanitov, Evgeny
- Issacs, Claudine
- Janavicius, Ramunas
- Lazaro, Conxi
- Blanco, Iganacio
- Tornero, Eva
- Navarro, Matilde
- Moysich, Kirsten B
- Karlan, Beth Y
- Gross, Jenny
- Olah, Edith
- Vaszko, Tibor
- Teo, Soo-Hwang
- Ganz, Patricia A
- Beattie, Mary S
- Dorfling, Cecelia M
- van Rensburg, Elizabeth J
- Diez, Orland
- Kwong, Ava
- Schmutzler, Rita K
- Wappenschmidt, Barbara
- Engel, Christoph
- Meindl, Alfons
- Ditsch, Nina
- Arnold, Norbert
- Heidemann, Simone
- Niederacher, Dieter
- Preisler-Adams, Sabine
- Gadzicki, Dorotehea
- Varon-Mateeva, Raymonda
- Deissler, Helmut
- Gehrig, Andrea
- Sutter, Christian
- Kast, Karin
- Fiebig, Britta
- Schäfer, Dieter
- Caldes, Trinidad
- de la Hoya, Miguel
- Nevanlinna, Heli
- Aittomäki, Kristiina
- Plante, Marie
- Spurdle, Amanda B
- Neuhausen, Susan L
- Ding, Yuan Chun
- Wang, Xianshu
- Lindor, Noralane
- Fredericksen, Zachary
- Pankratz, V Shane
- Peterlongo, Paolo
- Manoukian, Siranoush
- Peissel, Bernard
- Zaffaroni, Daniela
- Bonanni, Bernardo
- Bernard, Loris
- Dolcetti, Riccardo
- Papi, Laura
- Ottini, Laura
- Radice, Paolo
- Greene, Mark H
- Mai, Phuong L
- Andrulis, Irene L
- Glendon, Gord
- Ozcelik, Hilmi
- Pharoah, Paul D P
- Gayther, Simon A
- Simard, Jacques
- Easton, Douglas F
- Couch, Fergus J
- Chenevix-Trench, Georgia
- Peock, Susan
- Frost, Debra
- Ellis, Steve D
- Fineberg, Elena
- Platte, Radka
- Miedzybrodzka, Zosia
- Gregory, Helen
- Morrison, Patrick
- Jeffers, Lisa
- Cole, Trevor
- Ong, Kai-ren
- Hoffman, Jonathan
- Donaldson, Alan
- James, Margaret
- Paterson, Joan
- Downing, Sarah
- Taylor, Amy
- Murray, Alexandra
- Rogers, Mark T
- McCann, Emma
- Kennedy, M John
- Barton, David
- Porteous, Mary
- Drummond, Sarah
- Brewer, Carole
- Kivuva, Emma
- Searle, Anne
- Goodman, Selina
- Hill, Kathryn
- Davidson, Rosemarie
- Murday, Victoria
- Bradshaw, Nicola
- Snadden, Lesley
- Longmuir, Mark
- Watt, Catherine
- Gibson, Sarah
- Haque, Eshika
- Tobias, Ed
- Duncan, Alexis
- Izatt, Louise
- Jacobs, Chris
- Langman, Caroline
- Whaite, Anna
- Dorkins, Huw
- Barwell, Julian
- Adlard, Julian
- Serra-Feliu, Gemma
- Ellis, Ian
- Houghton, Catherine
- Evans, D Gareth
- Lalloo, Fiona
- Taylor, Jane
- Side, Lucy
- Male, Alison
- Berlin, Cheryl
- Eason, Jacqueline
- Collier, Rebecca
- Douglas, Fiona
- Claber, Oonagh
- Jobson, Irene
- Walker, Lisa
- McLeod, Diane
- Halliday, Dorothy
- Durell, Sarah
- Stayner, Barbara
- Eeles, Ros
- Shanley, Susan
- Rahman, Nazneen
- Houlston, Richard
- Bancroft, Elizabeth
- D'Mello, Lucia
- Page, Elizabeth
- Ardern-Jones, Audrey
- Kohut, Kelly
- Wiggins, Jennifer
- Castro, Elena
- Mitra, Anita
- Robertson, Lisa
- Cook, Jackie
- Quarrell, Oliver
- Bardsley, Cathryn
- Hodgson, Shirley
- Goff, Sheila
- Brice, Glen
- Winchester, Lizzie
- Eddy, Charlotte
- Tripathi, Vishakha
- Attard, Virginia
- Eccles, Diana
- Lucassen, Anneke
- Crawford, Gillian
- McBride, Donna
- Smalley, Sarah
- Sinilnikova, Olga
- Mazoyer, Sylvie
- Barjhoux, Laure
- Verny-Pierre, Carole
- Giraud, Sophie
- Léone, Mélanie
- Stoppa-Lyonnet, Dominique
- Gauthier-Villars, Marion
- Buecher, Bruno
- Houdayer, Claude
- Moncoutier, Virginie
- Belotti, Muriel
- Tirapo, Carole
- de Pauw, Antoine
- Bressac-de-Paillerets, Brigitte
- Remenieras, Audrey
- Byrede, Véronique
- Caron, Olivier
- Lenoir, Gilbert
- Bignon, Yves-Jean
- Urhammer, Nancy
- Lasset, Christine
- Bonadona, Valérie
- Hardouin, Agnès
- Berthet, Pascaline
- Sobol, Hagay
- Bourdon, Violaine
- Noguchi, Tetsuro
- Eisinger, François
- Coulet, Florence
- Colas, Chrystelle
- Soubrier, Florent
- Coupier, Isabelle
- Pujol, Pascal
- Peyrat, Jean-Philippe
- Fournier, Joëlle
- Révilliion, Françoise
- Vennin, Philippe
- Adenis, Claude
- Rouleau, Etienne
- Lidereau, Rosette
- Demange, Liliane
- Nogues, Catherine
- Muller, Danièle
- Fricker, Jean-Pierre
- Barouk-Simonet, Emmanuelle
- Bonnet, Françoise
- Bubien, Virginie
- Sevenet, Nicolas
- Longy, Michel
- Toulas, Christine
- Guimbaud, Rosine
- Gladieff, Laurence
- Feillel, Viviane
- Leroux, Dominique
- Dreyfus, Hélène
- Rebischung, Christine
- Peysselon, Megalie
- Coron, Fanny
- Faivre, Laurence
- Prieur, Fabienne
- Lebrun, Marine
- Kientz, Caroline
- Frénay, Marc
- Vénat-Bouvet, Laurence
- Delnatte, Capucine
- Mortemousque, Isabelle
- Lynch, Henry T
- Snyder, Carrie L
- Hogervorst, F B L
- Verhoef, S
- Verheus, M
- van't Veer, L J
- van Leeuwen, F E
- Collée, M
- van den Ouweland, A M W
- Jager, A
- Hooning, M J
- Tilanus-Linthorst, M M A
- Seynaeve, C
- van Asperen, C J
- Wijnen, J T
- Vreeswijk, M P
- Tollenaar, R A
- Devilee, P
- Ligtenberg, M J
- Hoogerbrugge, N
- Ausems, M G
- van der Luijt, R B
- Aalfs, C M
- van Os, T A
- Gille, J J P
- Waisfisz, Q
- Meijers-Heijboer, H E J
- Gomez-Garcia, E B
- van Roozendaal, C E
- Blok, Marinus J
- Caanen, B
- Oosterwijk, J C
- van der Hout, A H
- Mourits, M J
- Vasen, H F
- Thorne, Heather
- Niedermayr, Eveline
- Gill, Mona
- Collins, Lucine
- Gokgoz, Nalan
- Selander, Teresa
- Weerasooriya, Nayana
- Karlsson, Per
- Nordlilng, Margareta
- Bergman, Annika
- Einbeigi, Zakaria
- Stenmark-Askmalm, Marie
- Liedgren, Sigrun
- Borg, Ã…ke
- Loman, Niklas
- Olsson, HÃ¥kan
- Soller, Maria
- Jernström, Helena
- Harbst, Katja
- Henriksson, Karin
- Lindblom, Annika
- Arver, Brita
- von Wachenfeldt, Anna
- Liljegren, Annelie
- Barbany-Bustinza, Gisela
- Rantala, Johanna
- Melin, Beatrice
- Grönberg, Henrik
- Stattin, Eva-Lena
- Emanuelsson, Monica
- Ehrencrona, Hans
- Rosenquist, Richard
- Dahl, Niklas
- 5U01 CA113916, NCI NIH HHS, United States
- C12292/A11174, Cancer Research UK, United Kingdom
- C1287/A10118, Cancer Research UK, United Kingdom
- C1287/A11990, Cancer Research UK, United Kingdom
- C5047/A8385, Cancer Research UK, United Kingdom
- CA128978, NCI NIH HHS, United States
- CRN_87521, Canadian Institutes of Health Research, Canada
- HHSN261200744000C, PHS HHS, United States
- N02-CP-11019-50, NCI NIH HHS, United States
- N02-CP-65504, NCI NIH HHS, United States
- P30-CA051008, NCI NIH HHS, United States
- P50 CA116201, NCI NIH HHS, United States
- P50 CA116201, NCI NIH HHS, United States
- R01 CA074415, NCI NIH HHS, United States
- R01 CA083855, NCI NIH HHS, United States
- R01 CA102776, NCI NIH HHS, United States
- R01 CA128978, NCI NIH HHS, United States
- R01 CA128978, NCI NIH HHS, United States
- R01 CA140323, NCI NIH HHS, United States
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- R01 CA74415, NCI NIH HHS, United States
- R01-CA083855, NCI NIH HHS, United States
- R01-CA102776, NCI NIH HHS, United States
- RFA-CA-06-503, NCI NIH HHS, United States
- U01 CA069398, NCI NIH HHS, United States
- U01 CA069417, NCI NIH HHS, United States
- U01 CA069446, NCI NIH HHS, United States
- U01 CA069467, NCI NIH HHS, United States
- U01 CA069631, NCI NIH HHS, United States
- U01 CA069638, NCI NIH HHS, United States
- U01 CA113916, NCI NIH HHS, United States
- U01 CA69398, NCI NIH HHS, United States
- U01 CA69446, NCI NIH HHS, United States
- U01 CA69467, NCI NIH HHS, United States
- U01 CA69631, NCI NIH HHS, United States
- U01 CA69638, NCI NIH HHS, United States
- U01CA69417, NCI NIH HHS, United States