Citations 7
Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer
Rebbeck, Timothy R., Sinilnikova, Olga M., Healey, Sue, McGuffog, Lesley, Mazoyer, Sylvie , Chenevix‐Trench, Georgia , Easton, Douglas F. , Antoniou, Antonis C. , Nathanson, Katherine L. , Laitman, Yael , Kushnir, Anya, Berger, Raanan , Zidan, Jamal, Friedman, Eitan , Ehrencrona, Hans , Stenmark‐Askmalm, Marie , Einbeigi, Zakaria , Loman, Niklas, Harbst, Katja , Rantala, Johanna, Melin, Beatrice , Olopade, Olufunmilayo I. , Seldon, Joyce, Ganz, Patricia A. , Chan, Salina, Odunsi, Kunle , Gayther, Simon A. , Lu, Karen H., Mitchell, Gillian, Walsh, Christine , Lester, Jenny, Ross, Eric A. , Daly, Mary B., Whittemore, Alice S. , John, Esther M. , Miron, Alexander, Terry, Mary Beth , Goldgar, David E., Tihomirova, Laima, Dorfling, Cecilia M., Rensburg, Elizabeth J. van , Ding, Yuan Chun , Ejlertsen, Bent , Gerdes, Anne‐Marie , Osório, Ana , Benı́tez, Javier , Godino, Javier, Tejada, María‐Isabel , Durán, M. , Weitzel, Jeffrey N. , Bobolis, Kristie, Sand, Sharon , Fontaine, Annette Campbell, Savarese, Antonella , Pasini, Barbara , Peissel, Bernard , Zaffaroni, Daniela , Vignolo-Lutati, Francesca, Scuvera, Giulietta, Giannini, Giuseppe , Bernard, Loris, Genuardi, Maurizio , Radice, Paolo , Dolcetti, Riccardo , Manoukian, Siranoush , Pensotti, Valeria , Yannoukakos, Drakoulis , Torres, Diana , Rashid, Muhammad Usman , Hamann, Ute, Peock, Susan, Frost, Debra, Platte, Radka, Evans, D. Gareth , Eeles, Rosalind A. , Davidson, Rosemarie, Eccles, Diana , Cole, Trevor, Brewer, Carole, Hodgson, Shirley, Walker, Lisa, Porteous, Mary, Kennedy, M. John, Izatt, Louise , Adlard, Julian , Donaldson, Alan, Ellis, Steve, Sharma, Priyanka , Schmutzler, Rita K., Wappenschmidt, Barbara , Becker, Alexandra, Rhiem, Kerstin, Hahnen, Eric , Engel, Christoph , Meindl, Alfons , Engert, Stefanie, Ditsch, Nina , Plendl, Hans Jörg, Mundhenke, Christoph , Niederacher, Dieter , Fleisch, Markus C. , Sutter, Christian , Bartram, Claus R., Dikow, Nicola , Wang‐Gohrke, Shan , Gadzicki, Dorothea, Kast, Karin, Varon-Mateeva, Raymonda, Gehrig, Andrea, Houdayer, Claude , Belotti, Muriel, Gauthier‐Villars, Marion , Boutry‐Kryza, Nadia, Lasset, Christine, Sobol, Hagay , Peyrat, Jean‐Philippe, Muller, Danièle, Fricker, Jean‐Pierre , Collonge‐Rame, Marie‐Agnès , Mortemousque, Isabelle, Noguès, Catherine , Rouleau, Étienne , Paepe, Anne De , Poppe, Bruce , Claes, Kathleen , Piedmonte, Marion, Rodriguez, Gustavo C. , Wakely, Katie, Boggess, John F., Blank, Stephanie V. , Basil, Jack, Phillips, Kelly‐Anne , Caldés, Trinidad , Hoya, Miguel de la , Romero, Atocha , Aittomäki, Kristiina, Hout, Annemarie H. van der, Hogervorst, Frans B.L., Verhoef, Senno, Collée, J. Margriet, Seynaeve, Caroline, Oosterwijk, Jan C., Gille, Johannes J. P., Gómez, E. , Kets, Carolien M., Ausems, Margreet G.E.M. , Aalfs, Cora M. , Devilee, Peter , Mensenkamp, Arjen R. , Kwong, Ava , Oláh, Edith , Papp, J., Dı́ez, Orland , Darder, Esther , Blanco, Ignacio , Salinas, Mónica, Jakubowska, Anna , Lubiński, Jan , Jaworska–Bieniek, Katarzyna, Durda, Katarzyna, Sukiennicki, Grzegorz, Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Tołoczko‐Grabarek, Aleksandra, Złowocka-Perłowska, Elżbieta , Menkiszak, Janusz , Arason, Aðalgeir , Barkardóttir, Rósa B. , Simard, Jacques , Laframboise, Rachel , Montagna, Marco , Alducci, Elisa, Peixoto, Ana , Teixeira, Manuel R. , Spurdle, Amanda B. , Lee, Min Hyuk , Park, Sue K. , Kim, Sung-Won, Friebel, Tara M. , Lindor, Noralane M. , Guidugli, Lucia, Foretová, Lenka , Vijai, Joseph , Offit, Kenneth, Robson, Mark E. , Rau‐Murthy, Rohini, Kauff, Noah D. , Fink-Retter, A., Singer, Christian F., Gschwantler‐Kaulich, Daphne , Pfeiler, Georg , Tea, Muy‐Kheng M., Berger, Andreas, Greene, Mark H. , Mai, Phuong L., Imyanitov, Evgeny N., Senter, Leigha , Bojesen, Anders , Pedersen, Inge Søkilde , Skytte, Anne‐Bine , Sunde, Lone , Thomassen, Mads , Moeller, Sanne Traasdahl, Kruse, Torben A., Jensen, Uffe Birk , Caligo, Maria A. , Aretini, Paolo , Teo, Soo‐Hwang , Selkirk, Christina G. , Hulick, Peter J. , Andrulis, Irene L. , Lu, Karen H. , Durocher, Francine , Thorne, Heather , Pankratz, Vernon S, Wang, Xianshu , Mitra, Nandita , Wan, Fei , Paluch–Shimon, Shani , Huo, Dezheng , Nussbaum, Robert L. , Domchek, Susan M. , Arun, Banu , Karlan, Beth Y. , Godwin, Andrew K. , Pathak, Harsh B. , Chung, Wendy K. , Buys, Saundra S. , Janavičius, Ramūnas , Tung, Nadine , Steele, Linda Roslyn , Neuhausen, Susan L. , Hansen, Thomas van Overeem , Cajal, Teresa Ramón y , Godino, Javier, Bonanni, Bernardo , Gismondi, Viviana , Fostira, Florentia , Garber, Judy E. , Cook, Jackie A , Morrison, Patrick J. , Kennedy, M. John, Ellis, Steve, Meindl, Alfons , Arnold, Norbert , Steinemann, Doris , Beer, Marit A. de , Weber, Bernhard H. F. , Stoppa‐Lyonnet, Dominique , Houdayer, Claude , Damiola, Francesca , Lasset, Christine , Isaacs, Claudine , Leeneer, Kim De , Azodi, Masoud , Nevanlinna, Heli , Gille, Johannes J. P., Wijnen, Juul , Lázaro, Conxi , Gronwald, Jacek , Agata, Simona , Couch, Fergus J. , Pankratz, V. Shane , Tischkowitz, Marc D. , Singer, Christian F. , Rappaport, Christine , Mai, Phuong L., Toland, Amanda Ewart , Caligo, Maria A , Hulick, Peter J , Spurdle, Amanda B , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Adlard, Julian , Darder, Esther , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Joseph, Vijai , Olopade, Olufunmilayo I , Sunde, Lone , Menkiszak, Janusz , Jakubowska, Anna , Romero, Atocha , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Benitez, Javier , Engel, Christoph , Montagna, Marco , Robson, Mark , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Senter, Leigha , Rashid, Muhammad U , Gómez-García, Encarna B , Pasini, Barbara , Yannoukakos, Drakoulis , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Sharma, Priyanka , Phillips, Kelly-Anne , Terry, Mary Beth , Kwong, Ava , Rhiem, Kerstin
JAMA | April 7, 2015 | Volume: 313 | Issue: 13 | Pages: 1347
Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Peterlongo, Paolo , Chang-Claude, Jenny, Moysich, Kirsten B., Schmutzler, Rita K., Simard, Jacques , Soucy, Penny, Eeles, Rosalind A. , Easton, Douglas F. , Hamann, Ute, Wilkening, Stefan, Chen, Bowang , Rookus, Matti A. , Schmidt, Marjanka K. , Baan, Frederieke H. van der , Spurdle, Amanda B. , Walker, Logan C. , Lose, Felicity , Maia, Ana-Teresa , Montagna, Marco , Matricardi, Laura , Lubiński, Jan , Jakubowska, Anna , Gómez, E. , Olopade, Olufunmilayo I., Nathanson, Katherine L. , Rebbeck, Timothy R., Arun, Banu K., Karlan, Beth Y., Oršulić, Sandra , Lester, Jenny, Chung, Wendy K., Miron, Alex, Southey, Melissa C. , Goldgar, David E., Janavičius, Ramūnas , Dorfling, Cecilia M., Rensburg, Elizabeth J. van , Ding, Yuan Chun , Neuhausen, Susan L., Hansen, Thomas van Overeem , Gerdes, Anne‐Marie , Ejlertsen, Bent , Jønson, Lars, Osório, Ana , Martínez-Bouzas, Cristina, Benı́tez, Javier , Conway, Edye E., Blazer, Kathleen R. , Weitzel, Jeffrey N. , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Scuvera, Giulietta, Barile, Monica, Ficarazzi, Filomena , Mariette, Frédérique, Fortuzzi, Stefano , Viel, Alessandra , Giannini, Giuseppe , Papi, Laura , Martayan, Aline , Tibiletti, Maria Grazia , Radice, Paolo , Vratimos, Athanassios, Fostira, Florentia, Donaldson, Alan, Brewer, Carole, Foo, Claire, Evans, D. Gareth , Frost, Debra, Eccles, Diana , Brady, Angela, Adlard, Julian , Walker, Lisa, Izatt, Louise , Side, Lucy E., Rogers, Mark T., Porteous, Mary, Morrison, Patrick J., Platte, Radka, Davidson, Rosemarie, Hodgson, Shirley V. , Ellis, Steve, Cole, Trevor, EMBRACE, on behalf of, Claes, Kathleen , Maerken, Tom Van, Meindl, Alfons , Gehrig, Andrea, Sutter, Christian , Engel, Christoph , Niederacher, Dieter , Plendl, Hansjoerg, Kast, Karin, Rhiem, Kerstin, Ditsch, Nina , Varon-Mateeva, Raymonda, Wappenschmidt, Barbara , Wang-Gohrke, Shan, Paillerets, Brigitte Bressac–de , Buecher, Bruno , Delnatte, Capucine, Houdayer, Claude , Coupier, Isabelle, Barjhoux, Laure, Venat‐Bouvet, Laurence , Boutry‐Kryza, Nadia, Sinilnikova, Olga M., Caron, Olivier , Mazoyer, Sylvie , Belotti, Muriel, Collaborators, on behalf of GEMO Study, Piedmonte, Marion, Friedländer, Michael , Rodriguez, Gustavo C., Copeland, Larry J. , Hoya, Miguel de la , Segura, Pedro Pérez, Nevanlinna, Heli , Aittomäki, Kristiina, Os, Theo A.M. van, Meijers-Heijboer, Hanne E.J., Hout, Annemarie H. van der, Hoogerbrugge, Nicoline, Ausems, Margreet G.E.M. , Doorn, Helena C. van , Collée, Margriet , HEBON, on behalf of, Oláh, Edith , Dı́ez, Orland , Blanco, Ignacio , Lázaro, Conxi , Brunet, Joan , Feliubadaló, Lídia , Cybulski, Cezary, Durda, Katarzyna, Jaworska–Bieniek, Katarzyna, Sukiennicki, Grzegorz, Arason, Aðalgeir , Chiquette, Jocelyne , Teixeira, Manuel R. , Olswold, Curtis, Lindor, Noralane M. , Offit, Kenneth, Corines, Marina, Jacobs, Lauren , Robson, Mark E. , Zhang, Liying , Vijai, Joseph , Berger, Andreas, Singer, Christian F., Rappaport, Christine , Kaulich, Daphne Geschwantler, Pfeiler, Georg , Tea, Muy-Kheng M., Phelan, Catherine M., Greene, Mark H. , Mai, Phuong L., Rennert, Gad , Mulligan, Anna Marie , Glendon, Gord , Tchatchou, Sandrine, Andrulis, Irene L., Bojesen, Anders , Pedersen, Inge Søkilde , Thomassen, Mads , Jensen, Uffe Birk , Laitman, Yael , Rantala, Johanna, Wachenfeldt, Anna von , Ehrencrona, Hans , Askmalm, Marie Stenmark, Borg, Åke , Kuchenbaecker, Karoline B., McGuffog, Lesley, Barrowdale, Daniel , Healey, Sue, Lee, Andrew , Chenevix‐Trench, Georgia , Investigators, on behalf of KConFab, Antoniou, Antonis C. , Friedman, Eitan , Durocher, Francine , Olopade, Olufunmilayo I. , Hoogerbrugge, Nicoline , Thorne, Heather , Stenmark‐Askmalm, Marie , Wang, Xianshu , Chang‐Claude, Jenny, Moysich, Kirsten B. , Rudolph, Anja , Nussbaum, Robert L. , Domchek, Susan M. , Arun, Banu , By, Karlan, Chung, Wendy K. , Buys, Saundra S. , Garber, Judy E. , Cook, Jackie A , Tischkowitz, Marc D. , Barwell, Julian , Kennedy, Michael John , Ellis, Steve, EMBRACE, on behalf of, Godwin, Andrew K. , Meindl, Alfons , Steinemann, Doris , Arnold, Norbert , Wang-Gohrke, Shan, Stoppa‐Lyonnet, Dominique , Damiola, Francesca , Golmard, Lisa , Pujol, Pascal , Collaborators, on behalf of GEMO Study, Meijers‐Heijboer, Hanne , Vreeswijk, Maaike P.G. , Hoogerbrugge, Nicoline, HEBON, on behalf of, Gronwald, Jacek , Couch, Fergus J. , Szabo, Csilla I. , Singer, Christian F , Mai, Phuong L., Toland, Amanda Ewart , Pharoah, Paul D.P. , Investigators, on behalf of KConFab, Nevanlinna, H , Peterlongo, Paolo , Rennert, Gad , Spurdle, Amanda B , Teixeira, Manuel R , van Rensburg, Elizabeth J , Eccles, Diana , Moysich, Kirsten , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Adlard, Julian , Brunet, Joan , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , Joseph, Vijai , Matricardi, Laura , Olopade, Olufunmilayo I , Southey, Melissa C , Jakubowska, Anna , Schmidt, Marjanka K , Nathanson, Katherine L , Friedlander, Michael , Arason, Adalgeir , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Robson, Mark , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Feliubadaló, Lidia , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Manoukian, Siranoush , Lubinski, Jan , Rhiem, Kerstin
Cancer Epidemiology, Biomarkers & Prevention | October 22, 2014 | Volume: 24 | Issue: 1 | Pages: 308-316
Abstract Background:BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. Cancer Epidemiol Biomarkers Prev; 24(1); 308–16. ©2014 AACR.
BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk
Spurdle, Amanda B. , Whiley, Phillip J , Thompson, Bryony A. , Feng, Bing , Healey, Sue, Brown, Melissa A. , Pettigrew, Christopher A. , kConFab, Ausems, Margreet G.E.M. , Kattentidt-Mouravieva, A.A., Ouweland, Ans M.W. van den, Lindblom, Annika , Pigg, Maritta Hellström, Schmutzler, Rita K., Engel, Christoph , Meindl, Alfons , Caputo, Sandrine M. , Sinilnikova, Olga M., Lidereau, Rosette, collaborators, French COVAR group, Guidugli, Lucia, Hansen, Thomas van Overeem , Thomassen, Mads , Eccles, Diana M, Tucker, Kathy , Rensburg, Elizabeth J. van , Wappenschmidt, Barbara, Borg, Åke , Goldgar, David E. , Nathanson, Katherine L. , Devilee, Peter , Gómez, E. , Gerdes, Anne‐Marie , Luijt, Rob B. van der , Eccles, Diana , Mazoyer, Sylvie , Castéra, Laurent , Krieger, Sophie , kConFab, Asperen, Christi J. van , Meindl, Alfons , collaborators, French COVAR group, Couch, Fergus J. , Eccles, Diana M, Benı́tez, Javier , Domchek, Susan M. , Toland, Amanda Ewart , Vreeswijk, Maaike P.G. , Spurdle, Amanda B , van Rensburg, Elizabeth J , Eccles, Diana , van der Luijt, Rob B , Nathanson, Katherine L , Engel, Christoph , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Devilee, Peter , Lindblom, Annika
Journal of Medical Genetics | August 13, 2012 | Volume: 49 | Issue: 8 | Pages: 525-532
Background Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer. Methods Measures of genetic risk (report of family history, segregation) were assessed for 68 BRCA1 c.5096G>A p.Arg1699Gln (R1699Q) families recruited through family cancer clinics, comparing results with 34 families carrying the previously classified pathogenic BRCA1 c.5095C>T p.Arg1699Trp (R1699W) mutation at the same residue, and to 243 breast cancer families with no BRCA1 pathogenic mutation (BRCA-X). Results Comparison of BRCA1 carrier prediction scores of probands using the BOADICEA risk prediction tool revealed that BRCA1 c.5096G>A p.Arg1699Gln variant carriers had family histories that were less ‘ BRCA1 -like’ than BRCA1 c.5095C>T p.Arg1699Trp mutation carriers (p<0.00001), but more ‘ BRCA1 -like’ than BRCA-X families (p=0.0004). Further, modified segregation analysis of the subset of 30 families with additional genotyping showed that BRCA1 c.5096G >A p.Arg1699Gln had reduced penetrance compared with the average truncating BRCA1 mutation penetrance (p=0.0002), with estimated cumulative risks to age 70 of breast or ovarian cancer of 24%. Conclusions Our results provide substantial evidence that the BRCA1 c.5096G>A p.Arg1699Gln (R1699Q) variant, demonstrating ambiguous functional deficiency across multiple assays, is associated with intermediate risk of breast and ovarian cancer, highlighting challenges for risk modelling and clinical management of patients of this and other potential moderate-risk variants.
Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2
Gaudet, Mia M. , Antoniou, Antonis C. , Ramus, Susan J. , Kuchenbaecker, Karoline , Soucy, Penny, Chen, Xiaoqing, Kirchhoff, Tomas , McGuffog, Lesley, Barrowdale, Daniel , Healey, Sue, Sinilnikova, Olga M., Andrulis, Irene L. , Özçelik, Hilmi, Mulligan, Anna Marie , Thomassen, Mads , Gerdes, Anne‐Marie , Jensen, Uffe Birk , Skytte, Anne‐Bine , Kruse, Torben A., Caligo, Maria A. , Wachenfeldt, Anna von , Barbany, Gisela , Loman, Niklas, Soller, Maria , Ehrencrona, Hans , Karlsson, Per , Nathanson, Katherine L. , Rebbeck, Timothy R., Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Górski, Bohdan , Osório, Ana , Durán, M. , Tejada, María‐Isabel , Hamann, Ute, Hogervorst, Frans B.L., Os, Theo A. van, Leeuwen, Flora E. van , Meijers‐Heijboer, Hanne , Blok, Marinus J. , Kets, Marleen, Hooning, Maartje J. , Oldenburg, Rogier A., Ausems, Margreet G.E.M. , Peock, Susan, Frost, Debra, Ellis, Steve D., Platte, Radka, Fineberg, Elena, Evans, D. Gareth , Jacobs, Chris , Eeles, Rosalind A. , Adlard, Julian , Davidson, Rosemarie, Eccles, Diana M., Cole, Trevor, Paterson, Joan, Brewer, Carole, Douglas, Fiona, Hodgson, Shirley V. , Walker, Lisa, Porteous, Mary, Kennedy, M. John, Side, Lucy, Bove, Betsy, Fassy-Colcombet, Marion, Castéra, Laurent , Cornelis, François, Mazoyer, Sylvie , Léoné, Mélanie, Boutry‐Kryza, Nadia, Paillerets, Brigitte Bressac–de , Coupier, Isabelle, Delnatte, Capucine, Akloul, Linda, Lynch, Henry T., Snyder, Carrie, Daly, Mary B., Terry, Mary Beth , John, Esther M. , Miron, Alexander, Southey, Melissa C. , Goldgar, David E., Singer, Christian F., Rappaport, Christine , Tea, Muy‐Kheng M., Fink-Retter, Anneliese, Hansen, Thomas van Overeem , Nielsen, Finn C., Arason, Aðalgeir , Vijai, Joseph , Shah, Sohela, Sarrel, Kara , Piedmonte, Marion, Phillips, Kelly, Basil, Jack, Rubinstein, Wendy S. , Boggess, John F., Wakeley, Katie, Montagna, Marco , Imyanitov, Evgeny N., Janavičius, Ramūnas , Lázaro, Conxi , Blanco, Ignacio , Feliubadaló, Lídia , Brunet, Joan , Gayther, Simon A. , Odunsi, Kunle , Walsh, Christine , Oláh, Edith , Teo, Soo‐Hwang , Ganz, Patricia A. , Beattie, Mary, Rensburg, Elizabeth J. van , Dorfling, Cecelia M., Dı́ez, Orland , Kwong, Ava , Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph , Meindl, Alfons , Ditsch, Nina , Arnold, Norbert , Heidemann, Simone , Niederacher, Dieter , Preisler‐Adams, Sabine, Gadzicki, Dorothea, Varon-Mateeva, Raymonda, Deißler, Helmut , Gehrig, Andrea, Sutter, Christian , Kast, Karin, Fiebig, Britta, Heinritz, Wolfram, Caldes, Trinidad, Hoya, Miguel de la , Muranen, Taru , Nevanlinna, Heli , Spurdle, Amanda B. , Ding, Yuan Chun , Lindor, Noralane M. , Fredericksen, Zachary, Pankratz, V. Shane , Peterlongo, Paolo , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Barile, Monica, Bernard, Loris, Viel, Alessandra , Giannini, Giuseppe , Varesco, Liliana , Radice, Paolo , Greene, Mark H. , Mai, Phuong L., Easton, Douglas F., Chenevix‐Trench, Georgia , Offit, Kenneth, Simard, Jacques , Durocher, Francine , Eccles, Diana , Thorne, Heather , Phillips, Kelly‐Anne , Couch, Fergus J. , Beesley, Jonathan , Chen, Xiaoqing, Wang, Xianshu , Lee, Andrew , Domchek, Susan M. , Gronwald, Jacek , Benı́tez, Javier , Wijnen, Juul , Eccles, Diana M., Cook, Jackie A , Morrison, Patrick J. , Kennedy, M. John, Godwin, Andrew K. , Stoppa‐Lyonnet, Dominique , Caron, Olivier , Pujol, Pascal , Buys, Saundra S. , Chung, Wendy K. , Hopper, John L. , Singer, Christian F. , Robson, Mark E. , Phillips, Kelly, Toland, Amanda Ewart , Agata, Simona , Isaacs, Claudine , Pharoah, Paul D.P. , Karlan, Beth Y. , Meindl, Alfons , Varon-Mateeva, Raymonda, Caldes, Trinidad, Tischkowitz, Marc D. , Neuhausen, Susan L. , Mai, Phuong L., Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Ramus, Susan J , Spurdle, Amanda B , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Brunet, Joan , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Joseph, Vijai , Southey, Melissa C , Jakubowska, Anna , Muranen, Taru A , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Feliubadaló, Lidia , Hansen, Thomas van Overeem , Manoukian, Siranoush , Lubinski, Jan , Phillips, Kelly-Anne , Terry, Mary Beth , Kwong, Ava
Cancer Epidemiology, Biomarkers & Prevention | March 29, 2012 | Volume: 21 | Issue: 4 | Pages: 645-657
Abstract Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07–1.27; P = 7.42 × 10−4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73–0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94–1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05–1.29; P = 3.8 × 10−4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10–1.52; P = 1.8 × 10−3). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645–57. ©2012 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. Van, Blok, Marinus J. , Caanen, BA, Oosterwijk, Jan C., Hout, Annemarie H. van der, Mourits, M J E , Vasen, Hans F. A. , Easton, Douglas F., Peock, Susan, Cook, Margaret, Frost, Debra, Platte, Radka, Miedzybrodzka, Zosia , Gregory, Helen , Jeffers, Lisa, Cole, T, Ong, Kai-Ren, Hoffman, Jonathan , Donaldson, Alan, James, Margaret, Paterson, Joan, Downing, Sarah, 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, Edward S. , Duncan, Alexis E. , Izatt, Louise, Jacobs, Chris , Langman, Caroline, Whaite, Anna , Barwell, Julian, Adlard, Julian, Chu, Carol , Miller, Julie, Ellis, Ian O. , Evans, D. 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. Gareth, Lalloo, Fiona, Eeles, Ros, Bancroft, Elizabeth, D'Mello, Lucia, Sinilnikova, Olga, Sinilnikova, Olga, Giraud, Sophie, Léone, Mélanie, Mazoyer, Sylvie , Stoppa-Lyonnet, Dominique, Gauthier-Villars, Marion, Buecher, Bruno, Houdayer, Claude , Moncoutier, Virginie, Belotti, Muriel, Tirapo, Carole, Pauw, Antoine de, Bressac-de-Paillerets, Brigitte, Remenieras, Audrey, Byrde, Véronique, Lenoir, Gilbert, Bignon, Yves‐Jean , Uhrhammer, Nancy , Lasset, Christine, Bonadona, Valérie, Berthet, Pascaline, Bourdon, Violaine , Noguchi, Tetsuro, Eisinger, François, Coulet, Florence , Colas, Chrystelle , Soubrier, Florent , Coupier, Isabelle, Peyrat, Jean‐Philippe, Révillion, Françoise, Vennin, Philippe, Adenis, Claude, Rouleau, Étienne , Lidereau, Rosette, Demange, Liliane, Noguès, Catherine , Muller, Danièle, Fricker, Jean‐Pierre , Longy, Michel , Sevenet, Nicolas, Toulas, Christine , Guimbaud, Rosine, Gladieff, Laurence , Feillel, Viviane, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine , Coron, Fanny, Faivre, Laurence, Prieur, Fabienne, Lebrun, Marine, Ferrer, Sandra Fert, Frénay, Marc, Venat‐Bouvet, Laurence , Delnatte, Capucine, Mortemousque, Isabelle, Lynch, Henry T., Snyder, Carrie, Ejlertsen, Bent, Andersen, Mette Klarskov , Kjaergaard, Susanne, Sweet, Kevin , O’Connor, Michelle , Ramus, Susan, Pye, Carole, Wozniak, Eva , Varon-Mateeva, Raymonda, Kast, Karin, Preisler‐Adams, Sabine, Deißler, Helmut , Schönbuchner, Ines, Heinritz, Wolfram, Schäfer, Dieter, Aittomäki, Kristiina , Erkkilä, R.N. 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
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
AURKAF31I Polymorphism and Breast Cancer Risk inBRCA1andBRCA2Mutation Carriers: A Consortium of Investigators of Modifiers of BRCA1/2 Study
Sinilnikova, Olga M., Vierkant, Robert A. , Fredericksen, Zachary S., Coupier, Isabelle, Hughes, David J. , Hardouin, Agnès, Berthet, Pascaline, Peock, Susan, Cook, Margaret , Baynes, Caroline, Hodgson, Shirley, Porteous, Mary, Jakubowska, Anna , Spurdle, Amanda B. , kConFab, Schmutzler, Rita K., Versmold, Beatrix, Engel, Christoph , Meindl, Alfons , Sutter, Christian , Horst, Jürgen, Schaefer, Dieter, Offit, Kenneth, Kirchhoff, Tomas , Andrulis, Irene L. , Ilyushik, Eduard, Glendon, Gordon, Vasen, Hans F. A. , Borg, Åke , Backenhorn, Katja, Struewing, Jeffery P. , Greene, Mark H. , Nathanson, Katherine L. , Zikán, Michal , Foretová, Lenka , Sellers, Thomas A. , Lindor, Noralane M. , Nevanlinna, Heli , Tommiska, Johanna , Aittomäki, Kristiina, Hamann, Ute , Rashid, Muhammad Usman , Torres, Diana , Simard, Jacques , Durocher, Francine , Lynch, Henry T., Weitzel, Jeffrey N. , Olopade, Olufunmilayo I. , Narod, Steven A. , Daly, Mary B., Easton, Douglas F., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Evans, D. Gareth , Thorne, Heather , Couch, Fergus J. , Pankratz, V. Shane , Stoppa‐Lyonnet, Dominique , Morrison, Patrick J. , Lubiński, Jan , Gronwald, Jacek , kConFab, Meindl, Alfons , Devilee, Peter , Vreeswijk, Maaike P.G. , Neuhausen, Susan L. , Rebbeck, Timothy R. , Domchek, Susan M. , Wagner, Theresa Maria , Garber, Judy E. , Szabo, Csilla I. , Olson, Janet E. , Guénard, Frédéric , Isaacs, Claudine , Godwin, Andrew K. , Tomlinson, Gail Elizabeth , Nevanlinna, H , Spurdle, Amanda B , Vierkant, Robert A , Weitzel, Jeffrey N , Evans, D Gareth , Olopade, Olufunmilayo I , Jakubowska, Anna , Torres, Diana , Nathanson, Katherine L , Engel, Christoph , Simard, Jacques , Chenevix-Trench, Georgia , Rashid, Muhammad U , Hughes, David J
Cancer Epidemiology, Biomarkers & Prevention | July 12, 2007 | Volume: 16 | Issue: 7 | Pages: 1416-1421
AbstractThe AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1416–21)