Citations 156
Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer
Goode, Ellen L. , García‐Closas, Montserrat , Severi, Gianluca , Hein, Rebecca, Fredericksen, Zachary, Malats, Núria , Zamora, M. Pilar , Dörk, Thilo , Schürmann, Peter , Karstens, Johann H., Hillemanns, Peter , Cox, Angela , Brock, Ian W., Elliot, Graeme, Cross, Simon S. , Seal, Sheila, Turnbull, Clare , Renwick, Anthony, Rahman, Nazneen , Shen, Chen‐Yang , Yu, Jyh‐Cherng , Huang, Chiun‐Sheng , Hou, Ming‐Feng , Nordestgaard, Børge G. , Bojesen, Stig E. , Lanng, Charlotte, Alnæs, Grethe Grenaker, Kristensen, Vessela N. , Børrensen-Dale, Anne-Lise, Hopper, John L. , Dite, Gillian S. , Apicella, Carmel, Southey, Melissa C. , Lambrechts, Diether , Yesilyurt, Betül T., Floris, Giuseppe , Leunen, Karin, Sangrajrang, Suleeporn , Gaborieau, Valérie , McKay, James , Chang‐Claude, Jenny , Wang‐Gohrke, Shan , Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Barile, Monica, Giles, Graham G. , Baglietto, Laura , John, Esther M. , Miron, Alexander, Lissowska, Jolanta , Sherman, Mark E., Bogdanova, Natalia , Antonenkova, Natalia, Zalutsky, Iosif V., Rogov, Yuriy , Fasching, Peter A. , Ekici, Arif B. , Beckmann, Matthias W. , Brenner, Hermann , Stegmaier, Christa, Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Meindl, Alfons , Bartram, Claus R., Schmutzler, Rita K., Thomas, Gilles D., Hoover, Robert N. , Fletcher, Olivia , Gibson, Lorna J., dos‐Santos‐Silva, Isabel , Peto, Julian, Nickels, Stefan , Flesch‐Janys, Dieter, Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Schmidt, Marjanka K. , Veer, Laura van ‘t , Tollenaar, Rob A.�E.�M. , Dunning, Alison M. , Pooley, Karen A. , Schneeweiß, Andreas , Sohn, Christof , Burwinkel, Barbara , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Kang, Daehee , Noh, Dong‐Young , Ahn, Sei-Hyun, Hunter, David J. , Hankinson, Susan E. , Lindström, Sara, Chen, Xiaoqing, Beesley, Jonathan, Hamann, Ute, Justenhoven, Christina , Network, for the GENICA, Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, Hooning, Maartje J. , Hollestelle, Antoinette , Oldenburg, Rogier A., Tilanus‐Linthorst, Madeleine M.A., Хуснутдинова, Э. К. , Bermisheva, Marina , Prokofieva, Darya, Farahtdinova, Albina, Humphreys, Manjeet K., Wang, Qin , Chenevix‐Trench, Georgia , Easton, Douglas F. , Lambrechts, Diether , Milne, Roger L. , Couch, Fergus J. , Pérez, José Ignacio Arias , Benı́tez, Javier , Børrensen-Dale, Anne-Lise, Brennan, Paul , Chanock, Stephen Jacob , Figueroa, Jonine D. , Bayer, Christian , Müller, Heiko , Arndt, Volker , Mannermaa, Arto, Meindl, Alfons , Heil, Joerg , Anton‐Culver, Hoda , Ziogas, Argyrios , Broeks, Annegien , Veer, Laura J. van’t , Pharoah, Paul D.P. , Marmé, Frederik , Yoo, Keun-Young , Hankinson, Susan E. , Kraft, Peter , Chen, Xiaoqing, Harth, Volker , Network, for the GENICA, Olson, Janet E. , Wang, Xianshu , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Hillemanns, Peter , Radice, Paolo , Lissowska, Jolanta , John, Esther M , Southey, Melissa C , Malats, Nuria , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Pylkäs, Katri , Manoukian, Siranoush , Lubinski, Jan , Baglietto, Laura , Fletcher, Olivia , Bojesen, Stig E , Huang, Chiun-Sheng , Sawyer, Elinor J , Kang, Daehee
Cancer Epidemiology, Biomarkers & Prevention | October 6, 2011 | Volume: 20 | Issue: 10 | Pages: 2222-2231
Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.
Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers
Cox, David G. , Simard, Jacques , Sinnett, Daniel , Hamdi, Yosr , Soucy, Penny, Ouimet, Manon , Barjhoux, Laure, Verny-Pierre, Carole, McGuffog, Lesley , Healey, Sue, Greene, Mark H. , Mai, Phuong L., Andrulis, Irene L. , Network, Ontario Cancer Genetics, Thomassen, Mads , Gerdes, Anne‐Marie , Caligo, Maria A. , Friedman, Eitan , Laitman, Yael , Paluch, Shani Shimon, Borg, Åke , Karlsson, Per , Askmalm, Marie Stenmark, Bustinza, Gisela Barbany, Collaborators, SWE-BRCA, Nathanson, Katherine L. , Rebbeck, Timothy R., Hamann, Ute, Rookus, Matti A. , Ouweland, Ans M.W. van den, Ausems, Margreet G.E.M. , Aalfs, Cora M. , Gille, Hans J. J. P., HEBON, EMBRACE, Peock, Susan, Frost, Debra, Evans, D. Gareth , Eeles, Rosalind A. , Izatt, Louise , Adlard, Julian, Paterson, Joan, Eason, Jacqueline, Remon, Marie-Alice, Moncoutier, Virginie, Gauthier‐Villars, Marion , Lasset, Christine, Giraud, Sophie , Hardouin, Agnès, Berthet, Pascaline, Sobol, Hagay , Eisinger, François , Paillerets, Brigitte Bressac–de , Delnatte, Capucine, Collaborators, GEMO Study, Goldgar, David E., Miron, Alex, Özçelik, Hilmi, Southey, Melissa C. , Terry, Mary Beth , Registry, The Breast Cancer Family, Dressler, Anne-Catharina, Tea, Muy‐Kheng M., Hansen, Thomas van Overeem , Jóhannsson, Óskar Þór, Piedmonte, Marion, Rodriguez, Gustavo C. , Basil, Jack, Blank, Stephanie V. , Montagna, Marco , Blanco, Ignacio , Gayther, Simon A. , Moysich, Kirsten B., Schmutzler, Rita K., Wappenschmidt, Barbara , Engel, Christoph , Meindl, Alfons , Ditsch, Nina , Arnold, Norbert , Niederacher, Dieter , Sutter, Christian , Gadzicki, Dorothea, Fiebig, Britta, Caldes, Trinidad, Laframboise, Rachel , Nevanlinna, Heli , Chen, Xiaoqing, Spurdle, Amanda B. , Ding, Yuan Chun , Peterlongo, Paolo , Manoukian, Siranoush , Bernard, Loris, Radice, Paolo , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Mazoyer, Sylvie, Sinilnikova, Olga M., Sinilnikova, Olga M., Dumont, Martine, Mai, Phuong , Greene, MH, Glendon, Gord, Selander, Teresa, Weerasooriya, Nayana , Karlsson, Per, Nordling, Margareta , Bergman, Annika, Einbeigi, Zakaria , Stenmark-Askmalm, Marie, Liedgren, S, Borg, Åke, Loman, Niklas, Olsson, Håkan , Kristoffersson, Ulf , Harbst, Katja , Henriksson, Karin, Lindblom, Annika , Arver, Brita, Wachenfeldt, Anna von , Liljegren, Annelie, Rantala, Johanna, Melin, Beatrice , Grönberg, Henrik , Stattin, Eva‐Lena , Emanuelsson, Monica, Ehrencrona, Hans , Seidel‐Renkert, Antje, Hogervorst, Frans B.L., Verhoef, S., Verheus, Martijn, Veer, Laura J. van’t , Leeuwen, Flora E. van , Rookus, M.A., Collée, Margriet , Ouweland, A.M.W. van den, Jager, Agnes , Hooning, Maartje J. , Tilanus‐Linthorst, Madeleine M.A., Seynaeve, Caroline, Asperen, C.J. van, Tollenaar, R.A., Devilee, P., Ligtenberg, M.J., Hoogerbrugge, Nicoline , Ausems, M.G., Aalfs, C.M., Os, T.A. van, Gille, J.J.P., Waisfisz, Quinten , Meijers‐Heijboer, Hanne , Gómez, E. , Roozendaal, Cees E. 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Gareth, Lalloo, Fiona, Side, Lucy, Male, Alison , Berlin, Cheryl, Eason, Jacqueline , Collier, Rebecca, Douglas, Fiona, Claber, Oonagh, Jobson, Irene, Walker, Lisa, McLeod, Diane M., Halliday, Dorothy , Durell, Sarah, Stayner, Barbara, Eeles, Ros, Shanley, Susan, Rahman, Nazneen , Bancroft, Elizabeth, D'Mello, Lucia, Page, Elizabeth, Ardern‐Jones, Audrey, Castro, Elena , Robertson, Lisa , 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, Evans, D. 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Irja, Thorne, Heather , Niedermayr, Eveline, Perez-Segura, Pedro, Durocher, Francine , John, Esther M. , Adlard, Julian , Stenmark‐Askmalm, Marie , Faivre, Laurence , Szabo, Csilla I. , Mai, Phuong L., Network, Ontario Cancer Genetics, Kaufman, Bella , Collaborators, SWE-BRCA, Domchek, Susan M. , Benı́tez, Javier , Asperen, Christi J. van , Devilee, Peter , HEBON, EMBRACE, Peock, Susan, Frost, Debra, Adlard, Julian, Paterson, Joan, Eason, Jacqueline, Godwin, Andrew K. , Lasset, Christine , Berthet, Pascaline, Caron, Olivier , Collaborators, GEMO Study, Buys, Saundra S. , Registry, The Breast Cancer Family, Singer, Christian F. , Dressler, Anne Catharina, Toland, Amanda Ewart , Isaacs, Claudine , Meindl, Alfons , Caldes, Trinidad, Chen, Xiaoqing, Beesley, Jonathan , Neuhausen, Susan L. , Couch, Fergus J. , Wang, Xianshu , Stoppa‐Lyonnet, Dominique , Mazoyer, Sylvie, Sinilnikova, Olga M., Dumont, Martine , Karlsson, Per, Borg, Åke, Soller, Maria , Jernström, Helena , Barbany, Gisela , Torres, Diana , Rashid, Muhammad Usman , Rookus, M.A., Asperen, C.J. van, Wijnen, Juul , Vreeswijk, Maaike P.G. , Devilee, P., Ligtenberg, M.J., Ausems, M.G., Luijt, Rob B. van der , Aalfs, C.M., Os, T.A. van, Gille, J.J.P., Easton, Douglas F., Cook, Margaret, Morrison, Patrick J. , Cole, Trevor, James, Margaret, Taylor, Amy , McCann, Emma, Kennedy, M. John, Snadden, Lesley, Izatt, Louise, Dorkins, Huw , Barwell, Julian, Adlard, Julian, Houghton, Catherine E. , Evans, D. Gareth, Lalloo, Fiona, Taylor, Jane Elizabeth , Berlin, Cheryl, Eeles, Ros, Houlston, Richard S. , Bancroft, Elizabeth, D'Mello, Lucia, Kohut, Kelly , Wiggins, Jennifer M. , Mitra, Anita , Cook, Jackie A , Quarrell, Oliver , Crawford, Gillian, Evans, D. Gareth, Lalloo, Fiona, Eeles, Ros, Bancroft, Elizabeth, D'Mello, Lucia, Sinilnikova, Olga, Sinilnikova, Olga, Giraud, Sophie, Stoppa-Lyonnet, Dominique, Moncoutier, Virginie, Pauw, Antoine de, Bressac-de-Paillerets, Brigitte, Remenieras, Audrey, Lasset, Christine, Bonadona, Valérie, Eisinger, François, Pujol, Pascal , Fournier, Joëlle , Vennin, Philippe, Delnatte, Capucine, Ejlertsen, Bent , Kjærgaard, Susanne, Senter, Leigha , Craven, Caroline M. , Pharoah, Paul D.P. , Harrington, Patricia , Blomqvist, Carl , Heikkinen, Tuomas , Hoya, Miguel de la , Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Spurdle, Amanda B , Eccles, Diana , Moysich, Kirsten , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Southey, Melissa C , Nathanson, Katherine L , Engel, Christoph , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Faivre, Laurence , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Manoukian, Siranoush , Terry, Mary Beth , Lindblom, Annika , Ellis, Ian
Human Molecular Genetics | September 3, 2011 | Volume: 20 | Issue: 23 | Pages: 4732-4747
Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium†
García‐Closas, Montserrat , Humphreys, Manjeet K., Platte, Radka, Hopper, John L. , Southey, Melissa C. , Apicella, Carmel, Hammet, Fleur, Schmidt, Marjanka K. , Tollenaar, Rob A.�E.�M. , Veer, Laura J. van’t , Fasching, Peter A. , Beckmann, Matthias W. , Ekici, Arif B. , Strick, Reiner , Peto, Julian , dos‐Santos‐Silva, Isabel , Fletcher, Olivia , Johnson, Nichola , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Burwinkel, Barbara , Marmé, F., Schneeweiß, Andreas , Sohn, Christof , Bojesen, Stig E. , Flyger, Henrik, Nordestgaard, Børge G. , Zamora, M. Pilar , Brenner, Hermann , Rahman, Nazneen , Turnbull, Clare , Seal, Sheila, Renwick, Anthony, Brauch, Hiltrud , Justenhoven, Christina , Brüning, Thomas , Network, The GENICA, Chang‐Claude, Jenny , Hein, Rebecca, Wang‐Gohrke, Shan , Dörk, Thilo , Schürmann, Peter , Bremer, Michael , Hillemanns, Peter , Nevanlinna, Heli , Heikkinen, Tuomas , Aittomäki, Kristiina, Blomqvist, Carl , Bogdanova, Natalia , Antonenkova, Natalia, Rogov, Yuriy , Karstens, Johann H., Bermisheva, Marina , Prokofieva, Darya, Gantcev, Shamil Hanafievich, Хуснутдинова, Э. К. , Lindblom, Annika , Margolin, Sara , Chenevix‐Trench, Georgia , Chen, Xiaoqing, Group, for the kConFab AOCS Management, Mannermaa, Arto, Kosma, Veli‐Matti , Soini, Ylermi, Kataja, Vesa , Lambrechts, Diether , Yesilyurt, Betül T., Chrisiaens, Marie-Rose, Peeters, Stéphanie , Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Barile, Monica, Couch, Fergus, Diasio, Robert B. , Giles, Graham G. , Severi, Gianluca , Baglietto, Laura , Maclean, Catriona, Offit, Ken, Robson, Mark E. , Vijai, Joseph , Gaudet, Mia M., John, Esther M. , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, Andrulis, Irene L. , Knight, Julia A. , Mulligan, Anna Marie , O’Malley, Frances P., Brinton, Louise A. , Sherman, Mark E., Lissowska, Jolanta , Hooning, Maartje J. , Ouweland, Ans M.W. van den, Collée, J. Margriet, Czene, Kamila , Cox, Angela , Brock, Ian W., Reed, Malcolm , Cross, Simon S. , Dunning, Alison M. , Kang, Daehee , Yoo, Keun-Young, Noh, Dong‐Young , Ahn, Sei Hyun , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Sangrajrang, Suleeporn , Gaborieau, Valérie , Brennan, Paul , McKay, James , Shen, Chen‐Yang , Ding, Shian-ling, Hsu, Huan-Ming, Yu, Jyh-Cherng, Ashworth, Alan , Swerdlow, Anthony J. , Jones, Michael E. , Orr, Nick , Egan, Kathleen M. , Titus‐Ernstoff, Linda, Easton, Doug , Spurdle, Amanda B. , Webb, Penelope M. , DeFazio, Anna , Thorne, Heather , Lambrechts, Diether , Figueroa, Jonine D. , Broeks, Annegien , Benı́tez, Javier , Milne, Roger L. , Arias, José Ignacio , Müller, Heiko , Arndt, Volker , Network, The GENICA, Beesley, Jonathan , Chen, Xiaoqing, Group, for the kConFab AOCS Management, Mannermaa, Arto, Lee, Adam M. , Wang, Xianshu , Chanock, Stephen Jacob , Martens, John W.M. , Hall, Per N , Pharoah, Paul D.P. , Anton‐Culver, Hoda , Ziogas, Argyrios , Trentham‐Dietz, Amy , Newcomb, Polly A. , Fazio, Anna de , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Spurdle, Amanda B , Webb, Penelope M , Hillemanns, Peter , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , John, Esther M , Joseph, Vijai , Southey, Melissa C , Dunning, Alison M , Jakubowska, Anna , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Bogdanova, Natalia V , Robson, Mark , Chenevix-Trench, Georgia , Czene, Kamila , Pylkäs, Katri , Manoukian, Siranoush , Lubinski, Jan , Baglietto, Laura , Fletcher, Olivia , Bojesen, Stig E , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , Kang, Daehee
Human Molecular Genetics | August 18, 2011 | Volume: 20 | Issue: 23 | Pages: 4693-4706
Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer
Stevens, Kristen N., Vachon, Celine M. , Slager, Susan, Lesnick, Timothy G. , Olswold, Curtis, Fasching, Peter A. , Miron, Penelope , Eccles, Diana , Carpenter, Jane, Winqvist, Robert , Brauch, Hiltrud , Schmidt, Marjanka K. , Cox, Angela , Cross, Simon S. , Sawyer, Elinor J. , Hartmann, Arndt, Beckmann, Matthias W. , Schulz-Wendtland, Rüdiger, Ekici, Arif B. , Tapper, William , Gerty, Susan M. , Durcan, Lorraine , Graham, Nikki , Hein, Rebecca, Nickels, Stephan, Flesch‐Janys, Dieter, Heinz, Judith , Sinn, Hans‐Peter , Konstantopoulou, Irene , Pectasides, Dimitrios , Dimopoulos, Athanasios M., Clarke, Christine L. , Balleine, Rosemary L. , Fredericksen, Zachary, Diasio, Robert B. , Ross, Eric A. , Weaver, JoEllen , Rüdiger, Thomas , Dünnebier, Thomas, Ademuyiwa, Foluso O. , Kulkarni, Swati , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Ko, Yon‐Dschun, Limbergen, Erik Van, Janssen, Hilde, Peto, Julian , Fletcher, Olivia , Giles, Graham G. , Baglietto, Laura , Verhoef, Senno, Tomlinson, Ian , Kosma, Veli‐Matti , Greco, Dario , Blomqvist, Carl , Irwanto, Astrid , Liu, Jianjun , Blows, Fiona M., Dawson, Sarah‐Jane , Margolin, Sara , Mannermaa, Arto, Martin, Nicholas G. , Montgomery, Grant W. , Lambrechts, Diether , dos‐Santos‐Silva, Isabel , Severi, Gianluca , Hamann, Ute, Easton, Douglas F., Chang‐Claude, Jenny , Yannoukakos, Drakoulis , Nevanlinna, Heli , Dimopoulos, Meletios Α. , Purrington, Kristen S. , Lambrechts, Diether , Vachon, Celine M. , Lee, Adam M. , Godwin, Andrew K. , Ambrosone, Christine B. , Fostira, Florentia , Dimopoulos, Athanasios M., Fountzilas, George , Olson, Janet E. , Pathak, Harsh B. , Försti, Asta , Beesley, Jonathan , Mannermaa, Arto, Pharoah, Paul D.P. , Wang, Xianshu , Couch, Fergus J. , Nevanlinna, H , Lambrechts, Diether , Giles, Graham G , Eccles, Diana , Dimopoulos, Meletios A , Konstantopoulou, Irene , Martin, Nicholas G , Sinn, Peter , Lambrechts, Diether , Cox, Angela , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Ademuyiwa, Foluso O , Pylkäs, Katri , Yannoukakos, Drakoulis , Baglietto, Laura , Fletcher, Olivia , Purrington, Kristen S , Brauch, Hiltrud , Sawyer, Elinor J , Liu, Jing
Cancer Research | August 15, 2011 | Volume: 71 | Issue: 19 | Pages: 6240-6249
Abstract Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.
MicroRNA Processing and Binding Site Polymorphisms Are Not Replicated in the Ovarian Cancer Association Consortium
Permuth‐Wey, Jennifer, Chen, Zhihua , Lin, Hui‐Yi , Chen, Y. Ann , Barnholtz‐Sloan, Jill S. , Birrer, Michael J. , Cunningham, Julie M. , Fenstermacher, David, García‐Closas, Montserrat , Gayther, Simon A. , Bosquet, Jesús González , Iversen, Edwin S., McLaughlin, John, Menon, Usha , Narod, Steven A., Phelan, Catherine M., Ramus, Susan J. , Song, Honglin , Sutphen, Rebecca , Terry, Kathryn L. , Vierkant, Robert A. , Wentzensen, Nicolas , Lancaster, Johnathan M., Cheng, Jin Q. , Schildkraut, Joellen M. , Goode, Ellen L. , Sellers, Thomas A., Tsai, Ya-Yu , Chanock, Stephen Jacob , Cramer, Daniel W. , Fridley, Brooke L. , Gentry‐Maharaj, Aleksandra , Jim, Heather , McLaughlin, John, Risch, Harvey A. , Tyrer, Jonathan P. , Berchuck, Andrew , Pharoah, Paul D.P. , Ramus, Susan J , Vierkant, Robert A , Menon, Usha , Barnholtz-Sloan, Jill S , Lin, Hui-Yi , García-Closas, Montserrat , Bosquet, Jesus Gonzalez
Cancer Epidemiology, Biomarkers & Prevention | August 8, 2011 | Volume: 20 | Issue: 8 | Pages: 1793-1797
Abstract Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Common variants in these evaluated genes do not seem to be strongly associated with EOC risk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered. Cancer Epidemiol Biomarkers Prev; 20(8); 1793–7. ©2011 AACR.
Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
Schmidt, Marjanka K. , Sherman, Mark E., Hopper, John L. , Dite, Gillian S. , Apicella, Carmel, Smith, Letitia, Hammet, Fleur, Southey, Melissa C. , Veer, Laura van ‘t , Smit, Vincent T.H.B.M. , Fasching, Peter A. , Beckmann, Matthias W. , Jud, Sebastian M. , Ekici, Arif B. , Hartmann, Arndt , Hein, Alexander , Schulz-Wendtland, R., Burwinkel, Barbara , Schneeweiß, Andreas , Sinn, Hans‐Peter , Sohn, Christof , Tchatchou, Sandrine, Bojesen, Stig E. , Nordestgaard, Børge G. , Flyger, Henrik, Ørsted, David D., Kaur‐Knudsen, Diljit, Rodríguez, Primitiva Menéndez, Brauch, Hiltrud , Justenhoven, Christina , Ko, Yon‐Dschun, Network, The Genica, Hamann, Ute, Fischer, Hans‐Peter , Brüning, Thomas , Pesch, Beate, Chang‐Claude, Jenny , Wang‐Gohrke, Shan , Bremer, Michael , Karstens, Johann H., Hillemanns, Peter , Dörk, Thilo , Nevanlinna, Heli , Heikkinen, Tuomas , Blomqvist, Carl , Aittomäki, Kristiina, Aaltonen, Kirsimari, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kosma, Veli‐Matti , Kauppinen, Jaana M., Kataja, Vesa , Auvinen, Päivi , Eskelinen, Matti , Soini, Ylermi, Chenevix‐Trench, Georgia , Spurdle, Amanda B. , Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, kConFab, AOCS, Lambrechts, Diether , Claes, Bart, Vandorpe, T., Neven, Patrick , Wildiers, Hans , Flesch‐Janys, Dieter, Hein, Rebecca, Löning, Thomas , Kosel, Matthew , Fredericksen, Zachary S., Giles, Graham G. , Baglietto, Laura , Severi, Gianluca , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Kolonel, Laurence N. , Alnæs, Grethe Grenaker, Kristensen, Vessela, Børresen‐Dale, Anne‐Lise , Hunter, David J. , Hankinson, Susan E. , Andrulis, Irene L. , Mulligan, Anna Marie , O’Malley, Frances P., Huijts, Petra E.A., Tollenaar, Rob A.�E.�M. , Seynaeve, Caroline, Lissowska, Jolanta , Brinton, Louise A. , Pepłońska, Beata , Yang, Xiaohong R. , Hooning, Maartje J. , Hollestelle, Antoinette , Oldenburg, Rogier A., Jager, Agnes , Kriege, Mieke, Ozturk, Bahar, Czene, Kamila , Humphreys, Keith , Liu, Jianjun , Cox, Angela , Connley, Daniel, Cramp, Helen, Balasubramanian, Sabapathy P. , Reed, Malcolm , Dunning, Alison M. , Easton, Douglas F., Humphreys, Manjeet K., Caldas, Carlos , Blows, Fiona M., Driver, Kristy, Provenzano, Elena , Lubiński, Jan , Jakubowska, Anna , Huzarski, Tomasz , Byrski, Tomasz , Górski, Bohdan , Brennan, Paul , Sangrajrang, Suleeporn , Gaborieau, Valérie , Shen, Chen‐Yang , Hsiung, Chia‐Ni , Yu, Jyh‐Cherng , Chen, Shou‐Tung , Hsu, Giu‐Cheng, Hou, Ming‐Feng , Huang, Chiun‐Sheng , García‐Closas, Montserrat , Thorne, Heather , Hartikainen, Jaana M. , Bowtell, David D.L. , Lambrechts, Diether , Broeks, Annegien , Couch, Fergus J. , Veer, Laura J. van’t , Groot, Renate H. M. de , Marmé, Frederik , Milne, Roger L. , Pérez, José Ignacio Arias , Zamora, Pilar M. , Benı́tez, Javier , Network, The Genica, Heikkilä, Päivi , Mannermaa, Arto, Chen, Xiaoqing, kConFab, AOCS, Wang, Xianshu , Marchand, Loı̈c Le , Kristensen, Vessela N. , Devilee, Peter , Asperen, Christi J. van , Chanock, Stephen Jacob , Figueroa, Jonine D. , Leenders, Geert J.L.H. van , Hall, Per N , Cross, Simon S. , Cybulski, Cezary , Gronwald, Jacek , Anton‐Culver, Hoda , Ziogas, Argyrios , Pharoah, Paul D.P. , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Spurdle, Amanda B , Hein, Alexander , Hillemanns, Peter , Lissowska, Jolanta , Caldas, Carlos , Southey, Melissa C , Sinn, Peter , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Cox, Angela , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Chenevix-Trench, Georgia , Huzarski, Tomasz , Czene, Kamila , Bowtell, David D , Lubinski, Jan , Baglietto, Laura , Bojesen, Stig E , Huang, Chiun-Sheng , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Liu, Jing
Human Molecular Genetics | May 19, 2011 | Volume: 20 | Issue: 16 | Pages: 3289-3303
Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
Antoniou, Antonis C. , Sinilnikova, Olga M., Soucy, Penny, McGuffog, Lesley, Healey, Sue, Peterlongo, Paolo , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Cattaneo, Elisa , Barile, Monica, Pensotti, Valeria , Pasini, Barbara , Dolcetti, Riccardo , Giannini, Giuseppe , Putignano, Anna Laura , Varesco, Liliana , Radice, Paolo , Mai, Phuong L., Greene, Mark H. , Andrulis, Irene L. , Glendon, Gord , Özçelik, Hilmi, Thomassen, Mads , Gerdes, Anne‐Marie , Kruse, Torben A., Jensen, Uffe Birk , Crüger, Dorthe Gylling, Caligo, Maria A. , Laitman, Yael , Milgrom, Roni, Friedman, Eitan , Loman, Niklas, Harbst, Katja , Lindblom, Annika , Arver, Brita, Ehrencrona, Hans , Melin, Beatrice , SWE-BRCA, Nathanson, Katherine L. , Rebbeck, Timothy R., Jakubowska, Anna , Lubiński, Jan , Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Górski, Bohdan , Osório, Ana , Hamann, Ute, Hogervorst, Frans B.L., Rookus, Matti A. , Hooning, Maartje J. , Nelen, Marcel , Luijt, Rob B. van der , Os, Theo A.M. van, Meijers‐Heijboer, Hanne , Gómez, E. , HEBON, Peock, Susan, Cook, Margaret , Frost, Debra, Platte, Radka, Leyland, Jean, Evans, D. Gareth , Lalloo, Fiona, Eeles, Rosalind A. , Izatt, Louise , Adlard, Julian , Davidson, Rosemarie, Eccles, Diana , Ong, Kai-Ren, Douglas, Fiona, Paterson, Joan, Miedzybrodzka, Zosia , EMBRACE, Buecher, Bruno , Belotti, Muriel, Tirapo, Carole, Mazoyer, Sylvie , Barjhoux, Laure, Lasset, Christine , Leroux, Dominique, Faivre, Laurence, Bronner, Myriam , Prieur, Fabienne, Noguès, Catherine , Rouleau, Étienne , Coupier, Isabelle, Frénay, Marc, Collaborators, CEMO Study, Daly, Mary B., Terry, Mary Beth , John, Esther M. , Yassin, Yosuf, Miron, Alexander, Goldgar, David E., Registry, Breast Cancer Family, Singer, Christian F., Tea, Muy‐Kheng, Pfeiler, Georg , Dressler, Anne Catharina, Hansen, Thomas van Overeem , Jønson, Lars, Ejlertsen, Bent , Barkardóttir, Rósa B. , Kirchhoff, Tomas , Offit, Kenneth, Piedmonte, Marion, Rodriguez, Gustavo C. , Small, Laurie, Boggess, John F., Blank, Stephanie V. , Basil, Jack, Montagna, Marco , Tognazzo, Silvia , Imyanitov, Evgeny , Janavičius, Ramūnas , Lázaro, Conxi , Blanco, Ignacio , Sucheston, Lara, Walsh, Christine , Oláh, Edith , Bozsik, Anikó , Teo, Soo‐Hwang , Seldon, Joyce, Beattie, Mary, Rensburg, Elizabeth J. van , Sluiter, Michelle D., Dı́ez, Orland , Schmutzler, Rita K., Wappenschmidt, Barbara , Engel, Christoph , Meindl, Alfons , Ruehl, I., Varon-Mateeva, Raymonda, Kast, Karin, Deißler, Helmut , Niederacher, Dieter , Arnold, Norbert , Gadzicki, Dorothea, Schönbuchner, Ines, Caldes, Trinidad, Hoya, Miguel de la , Nevanlinna, Heli , Aittomäki, Kristiina, Dumont, Martine , Chiquette, Jocelyne , Chen, Xiaoqing, Beesley, Jonathan, Spurdle, Amanda B. , investigators, kConFab, Ding, Yuan Chun , Fredericksen, Zachary, Simard, Jacques , Easton, Douglas F. , Chenevix‐Trench, Georgia , CIMBA, on behalf of, Sutter, Christian , Vasen, Hans F. A. , Durocher, Francine , Rahman, Nazneen , Karlsson, Per , Nordling, Margareta , Olsson, Håkan , Hoogerbrugge, Nicoline , Waisfisz, Quinten , Barton, David , Tobias, Edward S. , Jacobs, Chris , Ellis, Ian O. , Castro, Elena , Lucassen, Anneke , Gladieff, Laurence , Thorne, Heather , Stenmark‐Askmalm, Marie , Faivre, Laurence , Kartsonaki, Christiana , Lee, Andrew , Mai, Phuong L., Kaufman, Bella , Paluch–Shimon, Shani , SWE-BRCA, Domchek, Susan M. , Gronwald, Jacek , Cajal, Teresa Ramón y , Fostira, Florentia , Andrés, Raquel , Benı́tez, Javier , Asperen, Christi J. van , Devilee, Peter , HEBON, Cook, Jackie A , Kennedy, Michael John , EMBRACE, Godwin, Andrew K. , Stoppa‐Lyonnet, Dominique , Pujol, Pascal , Collaborators, CEMO Study, Hopper, John L. , Buys, Saundra S. , Registry, Breast Cancer Family, Singer, Christian F. , Azodi, Masoud , Toland, Amanda Ewart , Agata, Simona , Pharoah, Paul D.P. , Karlan, Beth Y. , Meindl, Alfons , Caldes, Trinidad, Tischkowitz, Marc D. , Chen, Xiaoqing, investigators, kConFab, Neuhausen, Susan L. , Wang, Xianshu , Pankratz, V. Shane , Couch, Fergus J. , CIMBA, on behalf of, Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Spurdle, Amanda B , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , van der Luijt, Rob B , Jakubowska, Anna , Nathanson, Katherine L , Bozsik, Aniko , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Faivre, Laurence , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Pasini, Barbara , Manoukian, Siranoush , Lubinski, Jan , Terry, Mary Beth , Lindblom, Annika , Ellis, Ian
Human Molecular Genetics | May 19, 2011 | Volume: 20 | Issue: 16 | Pages: 3304-3321
LIN28B Polymorphisms Influence Susceptibility to Epithelial Ovarian Cancer
Permuth‐Wey, Jennifer, Tsai, Ya-Yu, Lin, Hui‐Yi , Chen, Y. Ann , Barnholtz‐Sloan, Jill S. , Birrer, Michael J. , Bloom, Gregory, Chen, Zhihua , Cunningham, Julie M. , Dagne, Getachew , Ebbert-Syfrett, Judith, Fenstermacher, David, García‐Closas, Montserrat , Gayther, Simon A. , Bosquet, Jesús González , Goode, Ellen L. , Iversen, Edwin S., Kong, William, McLaughlin, John, Menon, Usha , Monteiro, Álvaro N.A. , Narod, Steven A., Phelan, Catherine M., Qu, Xiaotao , Ramus, Susan J. , Schildkraut, Joellen M. , Song, Honglin , Stockwell, Heather, Sutphen, Rebecca , Terry, Kathryn L. , Vierkant, Robert A. , Wentzensen, Nicolas , Lancaster, Johnathan M., Cheng, Jin Q. , Sellers, Thomas A. , Kim, Donghwa , Chanock, Stephen Jacob , Cramer, Daniel W. , Fridley, Brooke L. , Ge, William H. , Gentry‐Maharaj, Aleksandra , Jim, Heather , McLaughlin, John, Pharoah, Paul D.P. , Risch, Harvey A. , Tyrer, Jonathan P. , Ramus, Susan J , Vierkant, Robert A , Menon, Usha , Monteiro, Alvaro N , Barnholtz-Sloan, Jill S , Lin, Hui-Yi , García-Closas, Montserrat , Bosquet, Jesus Gonzalez
Cancer Research | April 12, 2011 | Volume: 71 | Issue: 11 | Pages: 3896-3903
Abstract Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82–0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility. Cancer Res; 71(11); 3896–903. ©2011 AACR.
Abstract 870: Analysis of breast cancer risk factors by expression of tumor markers: results of 34 studies in the Breast Cancer Association Consortium (BCAC)
Yang, Xiaohong , Chang‐Claude, Jenny , Goode, Ellen L. , Gaudet, Mia M. , Fasching, Peter A. , Humphreys, Manjeet K., Easton, Douglas F. , Couch, Fergus J. , Nevanlinna, Heli , Milne, Roger L. , Schmidt, Marjanka K. , Spurdle, Amanda B. , Pharoah, Paul D.P. , Sherman, Mark E. , García‐Closas, Montserrat
Cancer Research | February 25, 2011 | Volume: 70 | Issue: 8_Supplement | Pages: 870-870
Abstract Epidemiologic studies suggest that breast cancer risk factor associations vary by tumor marker expression; however, individual studies have had limited power to address this question. We pooled data from up to 35,568 invasive breast cancer cases from 34 studies participating in the Breast Cancer Association Consortium (BCAC) to evaluate associations between established risk factors (age at menarche, nulliparity, age at first full time birth [AFFTB], body mass index [BMI] and family history) and breast cancer subtypes, defined by immunohistochemical expression of ER, PR, HER2, and basal markers (CK5/6 or CK5, EGFR). We used polychotomous logistic regression to evaluate relationships between risk factors and tumor subtypes in case-only analyses and to estimate case-control odds ratios and 95% confidence intervals for the associations between risk factors and specific tumor subtypes in 11 population-based studies including up to 12,841 cases and 17,032 controls. In case-only analyses, we found that reproductive risk factors were more common in hormone receptor positive tumors: early age at menarche was most strongly related to PR status (34.6% vs. 32.4% of women with age at menarche ≤12 years among PR+ and PR- cases, respectively, P= 0.001); whereas nulliparity, and late AFFTB in parous women were most strongly related to ER status (15.3% vs. 13.6% nulliparous women, 17.1% vs. 15.2% women with late AFFTB [≥30 years], among ER+ and ER- cases, respectively, P=2.6×10−6 for nulliparity and P=2.0×10−7 for late AFFTB). Nulliparity and late AFFTB were less common among triple negative (TN) tumors overall and among TN tumors expressing basal markers. Elevated BMI in women aged 50 years or younger was more common in ER-&PR- than ER+&PR+ tumors (17.0% vs 13.6% women with BMI ≥30, respectively, P=1.3×10−7), whereas above age 50 years, elevated BMI was more common in ER+&PR+ than ER+&PR- tumors (20.9% vs 16.7% women with BMI ≥30, respectively, P=2.8×10−8 comparing BMI ≥30 to BMI <25). In case-control analyses, early age at menarche was associated with increased risk of PR+ tumors; nulliparity and late AFFTB were most strongly associated with increased risk of (ER+ or PR+)&HER2- tumors, and did not increase the risk of TN tumors. Having a family history of breast cancer increased the risk of all tumor subtypes, although the association was strongest for TN tumors expressing basal markers. Our data provide convincing evidence for etiological heterogeneity with respect to breast cancer risk factors stratified by ER and PR status. Stratification by additional markers provides additional insights about etiologic differences in breast cancer risk. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 870.
Abstract 3860: New ovarian cancer susceptibility loci identified
Goode, Ellen L. , Song, Honglin , Lawrenson, Kate , Palmieri, Rachel T., Sellers, Thomas A. , Gayther, Simon A. , Chenevix‐Trench, Georgia , Ramus, Susan J. , Bolton, Kelly L. , Vierkant, Robert A. , Berchuck, Andrew , Tsai, Ya-Yu , Pharoah, Paul D.P. , Lawrenson, Kate
Cancer Research | February 25, 2011 | Volume: 70 | Issue: 8_Supplement | Pages: 3860-3860
Abstract Genome-wide association analyses have identified an ovarian cancer susceptibility locus near BNC2 at 9p22.2 (OR 0.82, p 5.1 × 10−19, Nat Genet 41:996-1000, 2009), based on 1,772 and 2,354 Stage I cases and controls, 4,803 and 5,237 Stage 2 cases and controls, and extensive Stage 3 analysis in independent samples. Here, we report on Stage 3 analysis of nine additional regions with Stage 2 results at p < 10−4. Stage 1 samples were genotyped using the Illumina 610Quad and imputed at up to 2 million SNPs; Stage 2 samples were genotyped on an Illumina iSelect of 22,790 SNPs. Stage 3 samples from 4,335 cases (including 2,197 serous subtype) and 5,951 controls (14 studies) were genotyped using Illumina or Sequenom at up to 32 SNPs on chromosomes 1, 2, 3, 7, 8, 11, and 17. No evidence of heterogeneity by study site was observed. Logistic regression revealed four regions with ordinal p ≤ 10−7 in all cases or serous subtype only. The most significant finding for all cases was for rs2072590 at 2q31.1 (all cases OR 1.15, p=8.1 × 10−13; serous only OR 1.19 p=9.0 × 10−13) which is located 3.8 kb 3-prime of HOXD3, a homeobox gene which also had an intronic SNP (rs2301301) with p=3.1 × 10−5 (all cases). Second, we observed a locus at 8q24.21 highlighted by rs10088218 (all cases OR 0.84, p=1.3 × 10−9; serous only OR 0.75 p=2.2 × 10−14). This locus resides on the opposite side of MYC and 1.3 Mb from the 8q24 regions harboring loci for other cancers, and is independent of the other cancer-associated variants (r2 < 0.02). Third, at 3q25.31, promising results were observed at rs2665390, a SNP intronic to TIPARP (TiPARP, TCDD-inducible poly(ADP-ribose) polymerase; all cases OR 1.19, p=8.7 × 10−7; serous only OR 1.26, p=3.2 × 10−8). Finally, at 17q21.32, rs9303542 was associated with risk particularly among serous cases (all cases OR 1.13, p=1.5 × 10−6; serous only OR 1.16 p=4.3 × 10−7); this SNP is intronic to SKAP1 (src kinase associated phosphoprotein 1). We evaluated the functional role of genes at these loci in ovarian cancer and normal ovarian epithelial cells and in an in vitro model of neoplastic initiation and progression from normal ovarian epithelial cells after CYMC and KRAS activation. Both BNC2 and TiPARP were down regulated in cancer versus normal cells (p=5 × 10−9 and p=3.4 × 10−5, respectively) suggesting that loss of function is required for cancer development. Over-expressing CMYC (at 8q24) induced neoplastic transformation of normal ovarian cells. Both BNC2 and TiPARP were down-regulated following CMYC over-expression and showed significant loss of function with further transformation after mutant KRAS activation (p=7.8 × 10−7 and p=6.3 × 10−4, respectively). These results emphasize the importance of genome-wide association studies and consortia for the identification of moderate-risk alleles in rare cancers. Importantly, our findings unravel the genetic components of this disease and suggest functionally-significant novel targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3860.