Wang‐Gohrke, Shan
Mayo Clinic
Memorial Sloan Kettering Cancer Center
Citations 23
Breast and Prostate Cancer Risks for MaleBRCA1andBRCA2Pathogenic Variant Carriers Using Polygenic Risk Scores
Barnes, Daniel R. , Silvestri, Valentina , Leslie, Goska , McGuffog, Lesley, Yang, Xin , Adlard, Julian , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L. , Arason, Aðalgeir , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barrowdale, Daniel , Belotti, Muriel, Berthet, Pascaline, Boonen, Susanne E. , Borg, Åke , Brady, Angela F., Brewer, Carole, Brunet, Joan , Bucalo, Agostino, Caldés, Trinidad , Cassingham, Hayley , Christensen, Lise Lotte , Cini, Giulia , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Leeneer, Kim De , Putter, Robin De , Valle, Jesús Del , Ding, Yuan Chun , Donaldson, Alan , Eason, Jacqueline , Eeles, Rosalind A. , Engel, Christoph , Evans, D. Gareth , Feliubadaló, Lídia , Frone, Megan N. , Frost, Debra, Gehrig, Andrea, Giraud, Sophie , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gregory, Helen , Groß, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas van Overeem , Hanson, Helen , Horváth, Judit , Investigators, KConFab, Investigators, HEBON, Izatt, Louise , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Johannsson, Oskar T., John, Esther M. , Kramer, Gero , Kroeldrup, Lone , Kruse, Torben A. , Lautrup, Charlotte Kvist , López‐Fernández, Adrià , Mai, Phuong L, Manoukian, Siranoush , Mátrai, Zoltán , Matricardi, Laura , Mebirouk, Noura, Meindl, Alfons , Montagna, Marco , Monteiro, Álvaro N.A. , Morrison, Patrick J. , Muranen, Taru , Nathanson, Katherine L. , Niederacher, Dieter , Oláh, Edith , Olopade, Olufunmilayo I. , Pedersen, Inge Søkilde , Peissel, Bernard , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pinto, Pedro, Porteous, Mary, Pottinger, Caroline , Pujana, Miquel Angel, Ramser, Juliane, Rantala, Johanna, Rogers, Mark T., Rønlund, Karina, Abajo, A.M. SÁnchez De, Shah, Payal D. , Sharif, Saba , Side, Lucy, Stadler, Zsofia, Steele, Linda , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teulé, Àlex , Thull, Darcy L. , Trainer, Alison H., Tripathi, Vishakha , Valentini, Virginia , Viel, Alessandra , Walker, Lisa, Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Whaite, Anna , Offit, Kenneth, Thomassen, Mads , Schmutzler, Rita K., Simard, Jacques , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Pujana, Miguel Ángel , Dennis, Joe , Yang, Xin , Adlard, Julian , Agnarsson, Bjarni A , Andrulis, Irene L , Arason, Adalgeir , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barkardottir, Rosa B , Barrowdale, Daniel , Benitez, Javier , Boonen, Susanne E , Bozsik, Aniko , Brennan, Paul , Brunet, Joan , Bucalo, Agostino , Caligo, Maria A , Campbell, Ian G , Cassingham, Hayley , Cini, Giulia , Claes, Kathleen B M , Coppa, Anna , Cortesi, Laura , Darder, Esther , de la Hoya, Miguel , de Putter, Robin , Del Valle, Jesús , Domchek, Susan M , Donaldson, Alan , Eason, Jacqueline , Engel, Christoph , Fostira, Florentia , Frone, Megan , Glendon, Gord , Godwin, Andrew K. , Greene, Mark H , Hahnen, Eric , Hanson, Helen , Izatt, Louise , Izquierdo, Angel , James, Paul , John, Esther M , Kroeldrup, Lone , Kruse, Torben A , Lazaro, Conxi , Lesueur, Fabienne , Matrai, Zoltan , Montagna, Marco , Monteiro, Alvaro N , Morrison, Patrick J , Muranen, Taru A , Nathanson, Katherine L , Neuhausen, Susan L. , Nevanlinna, H , Nguyen-Dumont, Tu , Niederacher, Dieter , Palli, Domenico , Parsons, Michael T , Perez-Segura, Pedro , Peterlongo, Paolo , Pinto, Pedro , Pottinger, Caroline , Radice, Paolo , Robson, Mark , Rump, Andreas , Sharif, Saba , Steele, Linda , Stoppa-Lyonnet, Dominique , Teixeira, Manuel R , Thull, Darcy L , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tommasi, Stefania , Toss, Angela , Tripathi, Vishakha , Valentini, Virginia , van Asperen, Christi J , Venturelli, Marta , Viel, Alessandra , Joseph, Vijai , Whaite, Anna , Simard, Jacques , Easton, Doug , Chenevix-Trench, Georgia , Ottini, Laura , Barnes, Daniel R , Leslie, Goska , Pujana, Miquel Angel , Eeles, Rosalind A , Evans, D Gareth , Matricardi, Laura , Olopade, Olufunmilayo I , Silvestri, Valentina , De Leeneer, Kim , Feliubadaló, Lidia , Hansen, Thomas van Overeem , Manoukian, Siranoush , Arnold, Norbert , Auber, Bernd , Balmañà, Judith , Barwell, Julian , Benı́tez, Javier , Bozsik, Anikó , Brady, Angela F., Buys, Saundra S. , Caligo, Maria A. , Campbell, Ian , Collaborators, GEMO Study, Collaborators, EMBRACE, Cook, Jackie A , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Gallagher, David James , Hentschel, Julia , Investigators, KConFab, Investigators, HEBON, Izquierdo, Á. , Lázaro, Conxi , Lesueur, Fabienne , Mai, Phuong L, Maxwell, Kara N. , Meindl, Alfons , Nevanlinna, Heli , Nguyen‐Dumont, Tú , Palli, Domenico , Parsons, Michael T. , Radice, Paolo , Robson, Mark E. , Rump, Andreas , Singer, Christian F. , Stoppa‐Lyonnet, Dominique , Asperen, Christi J. van , Vijai, Joseph , Zanna, Ines , Couch, Fergus J. , Ottini, Laura
JNCI: Journal of the National Cancer Institute | July 26, 2021 | Volume: 114 | Issue: 1 | Pages: 109-122
AbstractBackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
Glubb, Dylan M. , Thompson, Deborah J. , Aben, Katja K.H. , Alsulimani, Ahmad , Amant, Frédéric , Annibali, Daniela , Barricarte, Aurelio , Beckmann, Matthias W. , Bermisheva, Marina , Bernardini, Marcus Q. , Bischof, Katharina , Bodelón, Clara , Brand, Alison H. , Brinton, Louise A. , Bruinsma, Fiona , Burghaus, Stefanie , Cai, Hui , Carney, Michael E. , Chen, Chu , Chen, Xiao Qing, Chen, Zhihua , Cunningham, Julie M. , Vivo, Immaculata De , Dörk, Thilo , Edwards, Todd, Ekici, Arif B. , Ewing, Ailith , Fasching, Peter A. , Ferguson, Sarah, Flanagan, James M. , Fostira, Florentia, Gao, Bo , Gaudet, Mia M. , Gawełko, Jan , Goodman, Marc T. , Harter, Philipp , Hein, Alexander , Hildebrandt, Michelle A.T., Hillemanns, Peter , Høgdall, Claus , Holliday, Elizabeth , Huntsman, David G. , Huzarski, Tomasz , Jones, Michael E. , Kelley, Joseph L., Killeen, Jeffrey , Klapdor, Rüdiger , Köbel, Martin , Konopka, Bożena , Konstantopoulou, Irene , Kopperud, Reidun Kristin, Koti, Madhuri , Lambrechts, Diether , Lele, Shashikant , Lester, Jenny, Li, Andrew J., Liang, Dong , Liebrich, Clemens, Lipworth, Loren , Lissowska, Jolanta , Lu, Karen H., May, Taymaa, McGuire, Valerie , McNeish, Iain A. , Menon, Usha , Moysich, Kirsten B. , Odunsi, Kunle , Olsson, Håkan , Oršulić, Sandra , Osório, Ana , Park‐Simon, Tjoung‐Won , Pearce, Celeste Leigh, Podgórska, Agnieszka , Ramus, Susan J. , Riggan, Marjorie J. , Rothstein, Joseph H. , Runnebaum, Ingo B. , Scott, Rodney J. , Sellers, Thomas A. , Sieh, Weiva , Śpiewankiewicz, Beata, Sutphen, Rebecca , Teo, Soo‐Hwang , Thompson, Pamela J., Titus, Linda , Tone, Alicia , Edwards, Digna Velez, Vergote, Ignace , Wang, Zhaoming , Wang‐Gohrke, Shan , Group, for the OPAL Study, Group, for the AOCS, Whittemore, Alice S. , Wu, Xifeng , Wu, Anna H. , O’Mara, Tracy A. , Lu, Karen H. , Lambrechts, Diether , Barricarte, Aurelio , Bischof, Katharina , Bodelon, Clara , Brenton, James D , Brinton, Louise A , Buchanan, Daniel D , Cunningham, Julie M , De Vivo, Immaculata , Fazio, Anna de , Doherty, Jennifer A , Dörk, Thilo , Dunning, Alison M , Edwards, Todd , Ewing, Ailith , Fasching, Peter A , Flanagan, James M , Friedenreich, Christine M , Gaudet, Mia M , Gawełko, Jan , Gentry‐Maharaj, Aleksandra , Giles, Graham G , Glasspool, Rosalind , Harris, Holly R , Hein, Alexander , Heitz, Florian , Hillemanns, Peter , Jakubowska, Anna , Jones, Michael E , Karlan, Beth Y , Karnezis, Anthony , Kjaer, Susanne K , Klapdor, Rüdiger , Köbel, Martin , Konstantopoulou, Irene , Kupryjanczyk, Jolanta , Lambrechts, Diether , Lissowska, Jolanta , Lu, Lingeng , McAlpine, Jessica N , McNeish, Iain A , Menon, Usha , Nevanlinna, H , Orsulic, Sandra , Palli, Domenico , Park-Simon, Tjoung-Won , Permuth, Jennifer B , Ramus, Susan J , Runnebaum, Ingo B , Sieh, Weiva , Swerdlow, Anthony J , Szafron, Lukasz M , Teo, Soo H , Thompson, Pamela J , Thomsen, Liv Cecilie Vestrheim , Titus, Linda , Tumino, Rosario , Vanderstichele, Adriaan , Vergote, Ignace , Vierkant, Robert A , Webb, Penelope M , Winham, Stacey J , Spurdle, Amanda B , Lambrechts, Diether , Moysich, Kirsten , Wang, Zhaoming , O'Mara, Tracy A , Ekici, Arif B , Amant, Frederic , Høgdall, Claus K , Huzarski, Tomasz , Brand, Alison H , Goodman, Marc T , Attia, John , Berchuck, Andrew , Bjørge, Line , Brenton, James D. , Buchanan, Daniel D. , Bützow, Ralf C. , Chanock, Stephen Jacob , Chen, Xiao Qing, Cook, Linda S. , DeFazio, Anna , Doherty, Jennifer A. , Bois, Andreas du , Dunning, Alison M. , Dürst, Matthias , Fountzilas, George , Giles, Graham G. , Glasspool, Rosalind , Gronwald, Jacek , Harris, Holly R. , Heitz, Florian , Hildebrandt, Michelle A.T. , Høgdall, Estrid , Jakubowska, Anna , Jensen, Allan , Karlan, Beth Y. , Karnezis, Anthony N. , Хуснутдинова, Э. К. , Kjær, Susanne K. , Kraft, Peter , Kupryjańczyk, Jolanta , Larson, Melissa C. , Marchand, Loı̈c Le , Macciotta, Alessandra , Mattiello, Amalia , McAlpine, Jessica N. , Modugno, Francesmary , Nevanlinna, Heli , Palli, Domenico , Pejovic, Tanja B. , Permuth, Jennifer B. , Rebbeck, Timothy R. , Risch, Harvey A. , Senz, Janine , Setiawan, Veronica Wendy , Siddiqui, Nadeem , Swerdlow, Anthony J. , Szafron, Lukasz M. , Thomsen, Liv Cecilie Vestrheim , Tumino, Rosario , Turman, Constance , Vanderstichele, Adriaan , Edwards, Digna R. Velez , Vierkant, Robert A. , Webb, Penelope M. , Group, for the OPAL Study, Group, for the AOCS, White, Emily , Winham, Stacey J. , Yannoukakos, Drakoulis , Spurdle, Amanda B.
Cancer Epidemiology, Biomarkers & Prevention | November 3, 2020 | Volume: 30 | Issue: 1 | Pages: 217-228
Abstract Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10−7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Patel, Vivek , Busch, Evan L. , Cronin, Angel M., Leslie, Goska , McGuffog, Lesley, Adlard, Julian , Agata, Simona , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Arason, Aðalgeir , Artioli, Grazia, Arver, Brita, Auber, Bernd , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barroso, Alicia, Barrowdale, Daniel , Belotti, Muriel, Bertelsen, Birgitte , Blok, Marinus J. , Bodrogi, I., Bonadona, Valérie, Bondavalli, Davide , Boonen, Susanne E. , Borde, Julika , Borg, Åke , Bradbury, Angela R. , Brady, Angela, Brewer, Carole, Brunet, Joan , Buecher, Bruno , Caldés, Trinidad , Caliebe, Almuth , Calvello, Mariarosaria , Carrasco, Estela , Chan, Tsun Leung , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Daly, Mary B., Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Puppa, Lara Della , Ding, Yuan Chun , Ditsch, Nina , Donaldson, Alan, Dworniczak, Bernd , Easton, Douglas F. , Eccles, Diana M., Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , Engel, Christoph , Evans, D. Gareth , Faivre, Laurence, Faust, Ulrike , Feliubadaló, Lídia , Foretová, Lenka , Fountzilas, George , Frost, Debra, García‐Barberán, Vanesa , Gauthier‐Villars, Marion , Géczi, Lajos , Gehrig, Andrea, Gesta, Paul , Giannini, Giuseppe , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hamann, Ute, Hauke, Jan , Herold, Natalie, Hogervorst, Frans B.L., Honisch, Ellen, Hulick, Peter J. , Investigators, kConFab, Investigators, Hebon, Izatt, Louise , Jager, Agnes , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Jensen, Thomas D., Johannsson, Oskar T., John, Esther M. , Kang, Eunyoung , Kast, Karin, Kiiski, Johanna I. , Kim, Sung-Won, Ko, Kwang‐Pil , Konstantopoulou, Irene , Kramer, Gero , Krogh, Lotte, Kruse, Torben A., Kwong, Ava , Larsen, Mirjam, Lasset, Christine , Lautrup, Charlotte Kvist , Lee, Jihyoun , Lee, Jong Won, Lee, Min Hyuk , Lesueur, Fabienne , Liljegren, Annelie , Lindblom, Annika , Llovet, Patricia , López‐Fernández, Adrià , López‐Perolio, Irene, Lorca, Víctor , Loud, Jennifer T. , S.K., Edmond , Mai, Phuong L., Manoukian, Siranoush , Mari, Véronique , Martin, Lynn , Matricardi, Laura , Mebirouk, Noura, Medici, Veronica, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Miller, Clare , Gomes, D. Molina , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Navrátilová, Marie , Niederacher, Dieter , Nielsen, Finn C., Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Ong, Kai-Ren, Osório, Ana , Ott, Claus‐Eric , Park, Sue K. , Pedersen, Inge Søkilde , Peissel, Bernard , Peixoto, Ana , Peterlongo, Paolo , Petersen, Annabeth Høgh , Porteous, Mary, Pujana, Miguel Ángel , Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rizzolo, Piera , Rookus, Matti A. , Rossing, Caroline Maria, Ruddy, Kathryn J. , Santos, Catarina , Saule, Claire , Scarpitta, Rosa , Schmutzler, Rita K., Schuster, Hélène, Senter, Leigha , Seynaeve, Caroline, Shah, Payal D. , Silvestri, Valentina , Simard, Jacques , Skytte, Anne‐Bine , Snape, Katie , Solano, Ángela R. , Soucy, Penny, Sunde, Lone , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Thomassen, Mads , Tibiletti, Maria Grazia , Toland, Amanda Ewart, Torres, Diana , Trainer, Alison H., Baan, Frederieke H. van der , Kolk, Lizet E. van der, Hest, Liselotte P. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Viel, Alessandra , Vierstraete, Jeroen , Villa, Roberta, Wachenfeldt, Anna von , Wagner, Philipp , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Wieme, Greet , Yadav, Siddhartha , Yoon, Sook‐Yee , Zanzottera, Cristina , Zorn, Kristin K. , D’Amico, Anthony V. , Freedman, Matthew L. , Pomerantz, Mark M., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Ottini, Laura , Nielsen, Henriette Roed, Durocher, Francine , Eccles, Diana , Caputo, Sandrine M. , Faivre, Laurence , Leslie, Goska , Adlard, Julian , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barnes, Daniel R , Brunet, Joan , Caligo, Maria A , Campbell, Ian G , Claes, Kathleen B M , Darder, Esther , Dennis, Joe , Dworniczak, Bernd , Eeles, Rosalind A , Ehrencrona, Hans , Ejlertsen, Bent , Evans, D Gareth , Garre, Pilar , Greene, Mark H , Hulick, Peter J , Jager, Agnes , James, Paul , John, Esther M , Joseph, Vijai , Kim, Sung-Won , Konstantopoulou, Irene , Lesueur, Fabienne , Matricardi, Laura , Gomes, Denise Molina , Nevanlinna, H , Olopade, Olufunmilayo I , Palli, Domenico , Park, Sue K , Parsons, Michael T , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pujana, Miquel Angel , Ruddy, Kathryn J , Scarpitta, Rosa , Shah, Payal D , Silvestri, Valentina , Southey, Melissa C , Spurdle, Amanda B , Stoppa-Lyonnet, Dominique , Sunde, Lone , Teixeira, Manuel R , Teo, Soo H , Tommasi, Stefania , Toss, Angela , van der Luijt, Rob B , Vierstraete, Jeroen , Wieme, Greet , Yadav, Siddhartha , Antoniou, Antonis C , Eccles, Diana , Weitzel, Jeffrey N , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Boonen, Susanne E , Cortesi, Laura , Engel, Christoph , Hahnen, Eric , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Senter, Leigha , Faivre, Laurence , Rashid, Muhammad U , Calvello, Mariarosaria , Feliubadaló, Lidia , Hauke, Jan , Manoukian, Siranoush , Pomerantz, Mark M , Kwong, Ava , Lindblom, Annika , Friebel, Tara M. , Arnold, Norbert , Balmañà, Judith , Barnes, Daniel R. , Benı́tez, Javier , Bonadona, Valérie , Bonanni, Bernardo , Borg, Åke , Buys, Saundra S. , Cabezas-Camarero, Santiago , Caligo, Maria A. , Campbell, Ian , Carnevali, Ileana Wanda , Chu, Annie Tsz-Wai , Chung, Wendy K. , Cook, Jackie A , Couch, Fergus J. , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Fostira, Florentia , Gerdes, Anne‐Marie , Godwin, Andrew K. , Herold, Natalie, Hopper, John L. , Jensen, Thomas Dyrso, Vijai, Joseph , Lasset, Christine , Lázaro, Conxi , Lemke, Johannes R. , Mai, Phuong L., Meindl, Alfons , Miller, Clare, Moserle, Lidia , Mulligan, Anna Marie , Nevanlinna, Heli , Palli, Domenico , Parsons, Michael T. , Perez-Segura, Pedro , Radice, Paolo , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Shin, Vivian Yvonne , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Steele, Linda, Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Stradella, Agostina , Tischkowitz, Marc D. , Tognazzo, Silvia , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Luijt, Rob B. van der , Yannoukakos, Drakoulis , Neuhausen, Susan L. , Rebbeck, Timothy R.
Cancer Research | November 13, 2019 | Volume: 80 | Issue: 3 | Pages: 624-638
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Parsons, Michael T. , Tudini, Emma , Hahnen, Eric, Wappenschmidt, Barbara, Feliubadaló, Lídia , Aalfs, Cora M. , Agata, Simona, Aittomäki, Kristiina, Alducci, Elisa, Alonso‐Cerezo, María Concepción , Arnold, Norbert, Auber, Bernd , Austin, Rachel , Azzollini, Jacopo , Balmañà, Judith , Bartram, Claus R., Blümcke, Britta, Bonache, Sandra , Bonanni, Bernardo, Borg, Åke , Bortesi, Beatrice, Brunet, Joan , Bruzzone, Carla, Bucksch, Karolin , Cagnoli, Giulia , Caldés, Trinidad, Caliebe, Almuth , Calvello, Mariarosaria , Capone, Gabriele Lorenzo, Caputo, Sandrine M. , Carrasco, Estela , Caux‐Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia , Clarke, Edward , Cops, Elisa J., Cortesi, Laura , Couch, Fergus J., Darder, Esther , Debatin, Irmgard, Valle, Jesús Del , Delnatte, Capucine, Derive, Nicolas , Ditsch, Nina, Domchek, Susan M., Dutrannoy, Véronique, Eccles, Diana , Ehrencrona, Hans , Enders, Ute, Evans, D. Gareth , Farra, Chantal, Faust, Ulrike , Felbor, Ute , Feroce, Irène , Fine, Miriam, Galvão, Henrique C.R. , Gambino, Gaetana , Gehrig, Andrea, Gensini, Francesca , Germani, Aldo , Giesecke, J, Gómez, Carolina, Garcia, Encarna B., González, Sara , Grau, Èlia, Grill, Sabine , Groß, Eva, Guillaud‐Bataille, Marine , Gutiérrez‐Enríquez, Sara , Haaf, Thomas, Hackmann, Karl , Hansen, Thomas van Overeem , Harris, Marion, Hauke, Jan , Heinrich, T., Hellebrand, Heide, Herold, Karen, Honisch, Ellen, Horváth, Judit , Houdayer, Claude , Hübbel, Verena, Iglesias, Sílvia, Izquierdo, Á. , James, Paul A. , Janssen, Linda A.M., Jeschke, Udo, Kaulfuß, Silke , Keupp, Katharina, Kiechle, Marion , Kölbl, Alexandra C., Krieger, Sophie , Kruse, Torben A., Kvist, Anders , Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa , Lautrup, Charlotte Kvist , Ledig, Susanne, Leinert, Elena , Lim, Joanna , Loeffler, Markus, López‐Fernández, Adrià , Lucci‐Cordisco, Emanuela , Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica , Matricardi, Laura , Meindl, Alfons , Michelli, Rodrigo D., Moghadasi, Setareh , Moles‐Fernández, Alejandro , Montagna, Marco , Montalban, Gemma , Monteiro, Álvaro N.A. , Montes, Eva, Mori, Luigi , Müller, Clemens R., Mundhenke, Christoph , Naldi, Nadia, Nathanson, Katherine L. , Navarro, Matilde, Nichols, Cassandra , Niederacher, Dieter , Nielsen, Henriette Roed, Ong, Kai‐Ren , Pachter, Nicholas , Palmero, Edenir Inêz , Pedersen, Inge Søkilde , Peissel, Bernard , Pfeifer, Katharina, Pineda, Marta , Pohl‐Rescigno, Esther, Quante, Anne S. , Ramser, Juliane, Reis, Rui Manuel , Révillion, Françoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela , Rofes, Paula , Rump, Andreas , Salinas, Mónica, Abajo, A.M. SÁnchez De, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiß, Jochen, Solanes, Ares, Stiller, Mathias , Sullivan, Kelly J., Susman, Rachel , Sutter, Christian , Tavtigian, Sean V. , Teo, Soo‐Hwang , Thomassen, Mads, Tibiletti, Maria Grazia , Tognazzo, Silvia , Tornero, Eva , Törngren, Therese , Torres‐Esquius, Sara , Trainer, Alison, Tucker, Kathy , Asperen, Christi J. van, Mackelenbergh, Marion van , Varesco, Liliana, Vargas‐Parra, Gardenia , Varon, Raymonda, Vega, Ana , Velasco, Ángela, Vesper, Anne‐Sophie, Viel, Alessandra , Vreeswijk, Maaike P.G. , Wagner, Sebastian , Waha, Anke, Walker, Logan C., Walters, Rhiannon, Wang‐Gohrke, Shan , Weber, Bernhard , Weichert, Wilko , Wieland, Kerstin, Wöckel, Achim , Woodward, Emma R. , Zachariae, Silke , Zampiga, Valentina , Zeder-Göß, C, Investigators, KConFab, Lázaro, Conxi, Nicolo, Arcangela De , Radice, Paolo , Engel, Christoph , Schmutzler, Rita K., Goldgar, David E. , Manoukian, Siranoush , Gómez, E. , Houdayer, Claude , de la Hoya, Miguel , Diez, Orland , Eccles, Diana , Gutiérrez-Enríquez, Sara , Susman, Rachel , Tavtigian, Sean V , Toland, Amanda Ewart , Toss, Angela , Vega, Ana , Vreeswijk, Maaike P G , Woodward, Emma R , Radice, Paolo , Spurdle, Amanda B , James, Paul , Parsons, Michael T , Teo, Soo H , Monteiro, Alvaro N , Auber, Bernd , Azzollini, Jacopo , Brunet, Joan , Darder, Esther , Ehrencrona, Hans , Evans, D Gareth , Matricardi, Laura , Palmero, Edenir I , Nathanson, Katherine L , Pineda, Marta , Cini, Giulia , Cortesi, Laura , Del Valle, Jesús , Engel, Christoph , Izquierdo, Angel , Montagna, Marco , Rump, Andreas , Viel, Alessandra , Reis, Rui Manuel , Montalban, Gemma , Calvello, Mariarosaria , Feliubadaló, Lidia , Gómez-García, Encarna B , González, Sara , Hansen, Thomas van Overeem , Hauke, Jan , Zampiga, Valentina , De Nicolo, Arcangela , Manoukian, Siranoush , Li, Hongyan , Hahnen, Eric , Agata, Simona , Barbieri, Elena , Blanco, Ana , Bonanni, Bernardo , Bruzzone, Carla, Caligo, Maria A. , Carnevali, Ileana Wanda , Cavalli, Pietro , Concolino, Paola , Hoya, Miguel de la , Dean, Michael , Dı́ez, Orland , Farra, Chantal, Foulkes, William D. , Gerdes, Anne‐Marie , Gismondi, Viviana , Garcia, Encarna B., Guerrieri‐Gonzaga, Aliana , Guillaud-Bataille, Marine , Jeschke, Udo , Lewis, Alexandra L. , Loeffler, Markus, Meindl, Alfons , Moserle, Lidia , Navarro, Matilde, Nevanlinna, Heli , Papi, Laura , Perez-Segura, Pedro , Pohl‐Rescigno, Esther, Poplawski, Nicola Kazia , Porfirio, Berardino , Révillion, Françoise, Rhiem, Kerstin , Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Sullivan, Kelly J., Teulé, Àlex , Tischkowitz, Marc D. , Asperen, Christi J. van , Varesco, Liliana , Velasco, Àngela , Weber, Bernhard H. F., Wiesmüller, Lisa , Witzel, Isabell , Investigators, kConFab, Lázaro, Conxi, Spurdle, Amanda B. , Balmaña, Judith , Austin, Rachel
Human Mutation | May 27, 2019 | Volume: 40 | Issue: 9 | Pages: 1557-1578
Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study
Qian, Frank , Wang, Shengfeng , McGuffog, Lesley, Barrowdale, Daniel , Oosterwijk, Jan C., Evans, D. Gareth , Engel, Christoph , Kast, Karin, Aalfs, Cora M. , Adank, Muriel A. , Agnarsson, Bjarni A. , Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Ausems, Margreet G.E.M. , Azzollini, Jacopo , Barouk-Simonet, Emmanuelle, Belotti, Muriel, Benı́tez, Javier , Berger, Andreas, Borg, Åke , Bradbury, Angela R. , Brunet, Joan , Caldés, Trinidad , Caputo, Sandrine M. , Chiquette, Jocelyne , Collée, J. Margriet, Coupier, Isabelle, Daly, Mary B., Davidson, Rosemarie, Donaldson, Alan, Dorfling, Cecilia M., Eeles, Rosalind A. , Feliubadaló, Lídia , Foretová, Lenka , Fowler, Jeffrey M., Friedman, Eitan , Frost, Debra, Ganz, Patricia A. , García‐Barberán, Vanesa , Glendon, Gord , Gómez, E. , Hahnen, Eric , Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B., Hulick, Peter J. , Imyanitov, Evgeny N., Izatt, Louise , Jakubowska, Anna , Kaczmarek, Katarzyna, Kang, Eunyoung , Kets, Carolien M., Kim, Sung-Won, Kwong, Ava , Laitman, Yael , Lasset, Christine, Lee, Min Hyuk , Lee, Jong Won, Lee, Jihyoun , Lester, Jenny, Lesueur, Fabienne , Loud, Jennifer T. , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Niederacher, Dieter , Offit, Kenneth, Oláh, Edith , Ong, Kai-Ren, Ottini, Laura , Park, Sue K. , Peterlongo, Paolo , Pfeiler, Georg , Phelan, Catherine M., Poppe, Bruce , Pradhan, Nisha , Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rodriguez, Gustavo C. , Schmutzler, Rita K., Selkirk, Christina G. , Shah, Payal D. , Simard, Jacques , Sutter, Christian , Tan, Yen Y. , Teixeira, R , Teo, Soo‐Hwang , Terry, Mary Beth , Thomassen, Mads , Toland, Amanda Ewart, Tucker, Kathy , Engelen, Klaartje van , Rensburg, Elizabeth J. van , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Collaborators, GEMO Study, HEBON, EMBRACE, Greene, Mark H. , Rookus, Matti A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Goldgar, David E., Olopade, Olufunmilayo I. , Huo, Dezheng , Durocher, Francine , Teixeira, Manuel R. , Mitchell, Jonathan A. , Białkowska, Katarzyna , Hulick, Peter J , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Radice, Paolo , Weitzel, Jeffrey N , Azzollini, Jacopo , Brunet, Joan , Eeles, Rosalind A , Evans, D Gareth , Olopade, Olufunmilayo I , Jakubowska, Anna , Nathanson, Katherine L , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Mitchell, Jonathan S. , Leslie, Goska , Chung, Wendy K. , Adlard, Julian , Arun, Banu , Barwell, Julian , Borg, Åke , Buys, Saundra S. , Caligo, Maria A. , Campbell, Ian , Claes, Kathleen , Couch, Fergus J. , Dı́ez, Orland , Domchek, Susan M. , Garber, Judy E. , Godwin, Andrew K. , Gronwald, Jacek , Hopper, John L. , Isaacs, Claudine , Izquierdo, Á. , Karlan, Beth Y. , Kim, Sung-Won , Lasset, Christine , Lubiński, Jan , Meindl, Alfons , Miller, Austin , Morrison, Patrick J. , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Nussbaum, Robert L. , Robson, Mark E. , Singer, Christian F. , Giles, Graham G , Stoppa‐Lyonnet, Dominique , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Yannoukakos, Drakoulis , Collaborators, GEMO Study, HEBON, EMBRACE, Rebbeck, Timothy R. , Feliubadaló, Lidia , Gómez-García, Encarna B , Terry, Mary Beth , Kwong, Ava
JNCI: Journal of the National Cancer Institute | July 3, 2018 | Volume: 111 | Issue: 4 | Pages: 350-364
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
Friebel, Tara M. , Friedman, Eitan , Hamann, Ute, Huo, Dezheng , Kwong, Ava , Oláh, Edith , Olopade, Olufunmilayo I., Solano, Ángela R. , Teo, Soo‐Hwang , Thomassen, Mads , Weitzel, Jeffrey N. , Chan, TL, Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inêz , Park, Sue K. , Torres, Diana , Rensburg, Elizabeth J. van , McGuffog, Lesley, Aalfs, Cora M. , Abugattas, Julio E. , Aittomäki, Kristiina, Andrews, Lesley , Andrulis, Irene L., Arason, Aðalgeir , Arun, Banu, Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo , Balmañà, Judith , Barile, Monica, Barkardóttir, Rósa B. , Barrowdale, Daniel , Benı́tez, Javier , Berger, Andreas, Berger, Raanan , Blanco, Amie , Blazer, Kathleen R. , Blok, Marinus J. , Bonadona, Valérie , Bradbury, Angela R. , Brewer, Carole, Buecher, Bruno , Caldés, Trinidad, Caliebe, Almuth , Caligo, Maria A. , Caputo, Sandrine M. , Chiquette, Jocelyne , Claes, Kathleen , Collée, J. Margriet, Davidson, Rosemarie, Hoya, Miguel de la , Leeneer, Kim De , Pauw, Antoine De , Delnatte, Capucine, Ding, Yuan Chun , Ditsch, Nina , Dorfling, Cecilia M., Dworniczak, Bernd , Eason, Jacqueline , Easton, Douglas F. , Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , EMBRACE, Engel, Christoph , Engert, Stefanie, Evans, D. Gareth , Faivre, Laurence, Feliubadaló, Lídia , Ferrer, Sandra Fert, Foretová, Lenka , Fowler, Jeffrey M., Frost, Debra, Galvão, Henrique C.R. , Ganz, Patricia A. , Gauthier‐Villars, Marion , Gehrig, Andrea, Collaborators, GEMO Study, Gerdes, Anne‐Marie , Gesta, Paul , Giannini, Giuseppe , Giraud, Sophie , Glendon, Gord , Godwin, Andrew K., Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hauke, Jan , HEBON, Henderson, Alex, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Izatt, Louise , Izquierdo, Á. , Jakubowska, Anna , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Vijai, Joseph , Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Investigators, kConFab, Kim, Sung-Won, Konstantopoulou, Irene , Korach, Jacob, Laitman, Yael , Lasset, Christine, Lázaro, Conxi , Lee, Annette, Lee, Min Hyuk , Lester, Jenny, Lesueur, Fabienne , Liljegren, Annelie, Lindor, Noralane M. , Longy, Michel, Loud, Jennifer T. , Lu, Karen H. , Lubiński, Jan , Macháčková, Eva , Manoukian, Siranoush , Mari, Véronique , Martínez-Bouzas, Cristina, Mátrai, Zoltán , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Mickys, Ugnius, Montagna, Marco , Moysich, Kirsten B., Mulligan, Anna Marie , Musinsky, Jacob, Ngeow, Joanne , Niederacher, Dieter , Nielsen, Henriette Roed, Nielsen, Finn C., Offit, Kenneth, Öfverholm, Anna , Ong, Kai‐Ren , Osório, Ana , Papp, J., Pasini, Barbara , Pedersen, Inge Søkilde , Peixoto, Ana , Peruga, Nina, Peterlongo, Paolo , Pohl, Esther, Pradhan, Nisha , Prajzendanc, Karolina , Prieur, Fabienne, Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rodriguez, Gustavo C. , Rogers, Mark T., Rudaitis, Vilius , Schmidt, Ane Yde , Schmutzler, Rita K., Senter, Leigha , Shah, Payal D. , Side, Lucy, Simard, Jacques , Skytte, Anne‐Bine , Slavin, Thomas P. , Snape, Katie , Sobol, Hagay, Southey, Melissa C. , Sukiennicki, Grzegorz, Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomas, Abigail, Thull, Darcy L. , Tognazzo, Silvia , Toland, Amanda Ewart, Topka, Sabine , Trainer, Alison H. , Hout, Annemieke H. van der, Kolk, Lizet E. van der, Luijt, Rob B. van der , Heetvelde, Mattias Van , Varesco, Liliana, Varon‐Mateeva, Raymonda, Vega, Ana , Villarreal‐Garza, Cynthia , Wachenfeldt, Anna von , Walker, Lisa, Wang‐Gohrke, Shan , Wappenschmidt, Barbara, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K. , Selkirk, Christina G. , Hulick, Peter J. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Nathanson, Katherine L. , Durocher, Francine , Olopade, Olufunmilayo I. , Faivre, Laurence , Białkowska, Katarzyna , Caligo, Maria A , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Moysich, Kirsten , Vega, Ana , de la Hoya, Miguel , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , Joseph, Vijai , Konstantopoulou, Irene , Olopade, Olufunmilayo I , Southey, Melissa C , van der Luijt, Rob B , Jakubowska, Anna , Palmero, Edenir I , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Izquierdo, Angel , Lazaro, Conxi , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Senter, Leigha , Topka, Sabine , Rebbeck, Timothy R. , Couch, Fergus J. , Parsons, Michael T. , Leslie, Goska , Adlard, Julian , Agata, Simona , Arnold, Norbert , Bonanni, Bernardo , Buys, Saundra S. , Campbell, Ian , Chung, Wendy K. , Cook, Jackie A , Dı́ez, Orland , Domchek, Susan M. , Velázquez, Carolina , EMBRACE, Garber, Judy E. , Collaborators, GEMO Study, Gronwald, Jacek , HEBON, Hentschel, Julia , Hogervorst, Frans B.L., Isaacs, Claudine , John, Esther M. , Karlan, Beth Y. , Lasa, Adriana , Lasset, Christine , Liljegren, Annelie , Meindl, Alfons , Miller, Austin , Moysich, Kirsten B. , Neuhausen, Susan L. , Nevanlinna, Heli , Nguyen, Huu Phuc , Nussbaum, Robert L. , Papi, Laura , Pujol, Pascal , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Singer, Christian F. , Sobol, Hagay , Steele, Linda Roslyn , Steinemann, Doris , Szabo, Csilla I. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Wappenschmidt, Barbara , Weber, Bernhard H. F. , Yannoukakos, Drakoulis , Spurdle, Amanda B. , Faivre, Laurence , Rashid, Muhammad U , De Leeneer, Kim , Feliubadaló, Lidia , Hauke, Jan , Pasini, Barbara , Ngeow, Joanne , Manoukian, Siranoush , Lubinski, Jan , Terry, Mary Beth , Villarreal-Garza, Cynthia , Balmaña, Judith , Kwong, Ava
Human Mutation | February 15, 2018 | Volume: 39 | Issue: 5 | Pages: 593-620
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
Southey, Melissa C. , Goldgar, David E, Winqvist, Robert , Pylkäs, Katri , Michailidou, Kyriaki , Rensburg, Elizabeth J. van , Heikkinen, Tuomas , Hopper, John L. , Dörk, Thilo , Claes, Kathleen , Teo, Zhi L. , Radice, Paolo , Catucci, Irene, Peterlongo, Paolo , Odefrey, Fabrice, Dowty, James G., Schmidt, Marjanka K. , Hogervorst, Frans B.L., Verhoef, Senno, Carpenter, Jane, Clarke, Christine L. , Scott, Rodney J. , Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Marmé, F., Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Sanchez, Marie, Bojesen, Stig E. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Menéndez, Primitiva, Brenner, Hermann , Stegmaier, Christa, Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Muranen, Taru , Aittomäki, Kristiina, Blomqvist, Carl , Bogdanova, Natalia , Antonenkova, Natalia, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wauters, Els , Smeets, Dominiek, Beuselinck, Benoit , Floris, Giuseppe , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Vachon, Celine M. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei , Hunter, David J. , Lindström, Sara, Hankinson, Susan E. , Kraft, Peter , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Jukkola‐Vuorinen, Arja , Grip, Mervi, Kauppila, Saila , Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Darabi, Hatef, Eriksson, Mikael , Eccles, Diana M, Tapper, William , Gerty, Sue, Hooning, Maartje J. , Collée, J. Margriet, Tilanus‐Linthorst, Madeleine M.A., Li, Jingmei , Brand, Judith S. , Humphreys, Keith , Reed, Malcolm , Luccarini, Craig , Baynes, Caroline, Dunning, Alison M. , Hamann, Ute, Torres, Diana , Ulmer, Hans Ulrich, Rüdiger, Thomas , Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Slager, Susan, Yannoukakos, Drakoulis , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nick , Jones, Michael E. , González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Álvarez, Núria, Herrero, Daniel, Tessier, Daniel C., Vincent, Daniel , Bacot, François, Simard, Jacques , Dumont, Martine , Soucy, Penny, Eeles, Rosalind A. , Muir, Kenneth , Grönberg, Henrik , Schleutker, Johanna , Nordestgaard, Børge G. , Weischer, Maren , Travis, Ruth C. , Neal, David E. , Donovan, Jenny , Hamdy, Freddie C. , Stanford, Janet L. , Blot, William J. , Thibodeau, Stephen N. , Schaid, Daniel J. , Kelley, Joseph L., Maier, Christiane, Kibel, Adam S. , Butterbach, Katja, Kaneva, Radka , Batra, Jyotsna , Teixeira, Manuel R. , Olama, Ali Amin Al , Benlloch, Sara, Hartmann, Arndt , Hein, Alexander , Ruebner, Matthias , Lambrechts, Diether , Nieuwenhuysen, Els Van , Vergote, Ignace , Lambretchs, Sandrina, Rossing, Mary Anne, Nickels, Stefan , Eilber, Ursula, Wang‐Gohrke, Shan , Odunsi, Kunle , Sucheston‐Campbell, Lara, Friel, Grace , Lurie, Galina, Killeen, Jeffrey , Goodman, Marc T. , Runnebaum, Ingo B., Hillemanns, Peter , Pelttari, Liisa M. , Edwards, Robert P., Ness, Roberta B., Moysich, Kirsten B., Heitz, Florian , Harter, Philipp , Kommoss, Stefan , Walsh, Christine , Lester, Jenny, Jensen, Allan , Høgdall, Estrid , Peissel, Bernard , Bernard, Loris, Goode, Ellen L. , Vierkant, Robert A. , Cunningham, Julie M. , Fogarty, Zachary C. , Kalli, Kimberly R., Liang, Dong , Lu, Karen H., Hildebrandt, Michelle A.T., Wu, Xifeng , Levine, Douglas A. , Bisogna, Maria, Iversen, Edwin S., Marks, Jeffrey R. , Akushevich, Lucy , Schildkraut, Joellen M. , Terry, Kathryn L. , Stampfer, Meir J. , Tworoger, Shelley S. , Olson, Sara H. , Salvesen, Helga B., Altena, Anne M. van , Aben, Katja K.H. , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Bean, Yukie T., Kelemen, Linda E., Le, Nhu D. , Górski, Bohdan , Menkiszak, Janusz , Høgdall, Claus , Lundvall, Lene, Nedergaard, Lotte , Engelholm, Svend Aage, Dicks, Ed , Campbell, Ian , McNeish, Iain A. , Whittemore, Alice S. , Rothstein, Joseph H. , McGuire, Valerie, Sieh, Weiva , Cai, Hui , Teten, Rachel Threet, Sutphen, Rebecca , McLaughlin, John R, Narod, Steven A., Phelan, Catherine M., Monteiro, Álvaro N.A. , Fenstermacher, David, Lin, Hui‐Yi , Sellers, Thomas A. , Chen, Y. Ann , Chen, Zhihua , Gayther, Simon A. , Ramus, Susan J. , Menon, Usha , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Moes-Sosnowska, Joanna , Kupryjańczyk, Jolanta , Song, Honglin , Winship, Ingrid , Chenevix‐Trench, Georgia , Tavtigian, Sean V. , Easton, Doug , Lu, Karen H. , Durocher, Francine , Eccles, Diana , Lambrechts, Diether , Vachon, Celine, Pankratz, Vernon S, Thibodeau, Stephen, Goldgar, David E, Couch, Fergus J. , Tischkowitz, Marc D. , Foulkes, William D. , Dennis, Joe , Nevanlinna, Heli , Reis‐Filho, Jorge S. , Tsimiklis, Helen , Broeks, Annegien , dos‐Santos‐Silva, Isabel , Yang, Rongxi , Ménégaux, F. , Sanchez, Marie, Pérez, José Ignacio Arias , Anton‐Culver, Hoda , Neuhausen, Susan L. , Ziogas, Argyrios , Clarke, Christina A. , Arndt, Volker , Mannermaa, Arto, Spurdle, Amanda B. , Group, Australian Ovarian Cancer Study, Rudolph, Anja , Seibold, Petra , Olson, Janet E. , Vachon, Celine M. , Pankratz, V. Shane , Marchand, Loı̈c Le , Kristensen, Vessela N. , Hankinson, Susan E. , Hollestelle, Antoinette , Chanock, Stephen Jacob , Czene, Kamila , Eriksson, Mikael , Eccles, Diana M, Rafiq, Sajjad , Hooning, Maartje J. , Martens, John W.M. , Hall, Per N , Cox, Angela , Toland, Amanda Ewart , Ambrosone, Christine B. , Wiklund, Fredrik E. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong, Kote‐Jarai, Zsofia , Renner, Stefan P. , Doherty, Jennifer A. , Wilkens, Lynne R. , Bützow, Ralf C. , Modugno, Francesmary , Moysich, Kirsten B., Bois, Andreas du , Karlan, Beth Y. , Kjær, Susanne K. , Bonanni, Bernardo , Fridley, Brooke L. , Larson, Melissa C. , Hildebrandt, Michelle A.T. , Dao, Fanny , Berchuck, Andrew , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Orlow, Irene , Bjørge, Line , Pejovic, Tanja B. , Brooks‐Wilson, Angela , Cook, Linda S. , Gronwald, Jacek , Tyrer, Jonathan P. , Paul, James , Siddiqui, Nadeem , Glasspool, Rosalind , Shu, Xiao‐Ou , McLaughlin, John R, Permuth, Jennifer B. , Gentry‐Maharaj, Aleksandra , Berg, David Van Den , Pharoah, Paul D.P. , Giles, Graham G. , Milne, Roger L. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Tworoger, Shelley S , van Rensburg, Elizabeth J , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Radice, Paolo , Lissowska, Jolanta , Claes, Kathleen B M , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Menkiszak, Janusz , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Lin, Hui-Yi , Fogarty, Zachary C , Dunning, Alison M , Heitz, Florian , Jakubowska, Anna , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , Li, Jingmei , Muranen, Taru A , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Winship, Ingrid M , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Batra, Jyotsna , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Goodman, Marc T , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Journal of Medical Genetics | September 5, 2016 | Volume: 53 | Issue: 12 | Pages: 800-811
Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer
Hampras, Shalaka , Sucheston‐Campbell, Lara, Cannioto, Rikki , Chang‐Claude, Jenny , Dörk, Thilo , Hillemanns, Peter , Preus, Leah, Knutson, Keith L. , Wallace, Paul K. , Friel, Grace , Davis, Warren , Nesline, Mary , Pearce, Celeste Leigh, Kelemen, Linda E. , Goodman, Marc T. , Terry, Kathryn L. , Schoof, Nils , Eng, Kevin H., Clay‐Gilmour, Alyssa , Joseph, Janine M. , Aben, Katja K.H. , Antonenkova, Natalia, Baker, Helen , Bean, Yukie T., Beckmann, Matthias W. , Bisogna, Maria, Bogdanova, Natalia , Brinton, Louise A. , Bruinsma, Fiona , Campbell, Ian , Carty, Karen , Dansonka‐Mieszkowska, Agnieszka , Despierre, Evelyn, Dicks, Ed , Easton, Doug , Eccles, Diana , Edwards, Robert P., Ekici, Arif B. , Fasching, Peter A. , Gao, Yu‐Tang , Harrington, Patricia, Harter, Philipp , Hasmad, Hanis Nazihah, Hein, Alexander , Heitz, Florian , Hildebrandt, Michelle A.T., Høgdall, Claus , Høgdall, Estrid , Hosono, Satoyo , Iversen, Edwin S., Jakubowska, Anna , Jensen, Allan , Ji, Bu‐Tian , Kellar, Melissa, Kelley, Joseph L., Kiemeney, Lambertus A. , Klapdor, Rüdiger , Kolomeyevskaya, Nonna, Krakstad, Camilla , Kruszka, Bridget, Kupryjańczyk, Jolanta , Lambrechts, Diether , Lambrechts, Sandrina, Le, Nhu D. , Lee, Alice W. , Lele, Shashikant , Leminen, Arto, Lester, Jenny, Levine, Douglas A. , Liang, Dong , Lissowska, Jolanta , Liu, Song , Lu, Karen, Lubiński, Jan , Lundvall, Lene, Massuger, Leon F.A.G. , Matsuo, Keitaro , McGuire, V., McLaughlin, John R., McNeish, Iain A. , Menon, Usha , Moes-Sosnowska, Joanna , Narod, Steven A., Nedergaard, Lotte , Nickels, Stefan , Olson, Sara H. , Weber, Rachel Palmieri , Paul, James , Pelttari, Liisa M. , Perkins, Barbara, Permuth‐Wey, Jenny, Pike, Malcolm C., Plisiecka-Hałasa, Joanna, Rossing, Mary Anne, Rothstein, Joseph H. , Runnebaum, Ingo B. , Rzepecka, Iwona K. , Salvesen, Helga B., Schernhammer, Eva , Schmitt, Kristina, Schwaab, Ira, Shvetsov, Yurii B. , Sieh, Weiva , Song, Honglin , Southey, Melissa C. , Tangen, Ingvild L. , Teo, Soo‐Hwang , Thompson, Pamela J., Timorek, Agnieszka, Tworoger, Shelley S. , Altena, Anna M. van, Vergote, Ignace , Vierkant, Robert A. , Walsh, Christine , Wang‐Gohrke, Shan , Wentzensen, Nicolas, Whittemore, Alice S. , Wicklund, Kristine G. , Wu, Anna H. , Wu, Xifeng , Woo, Yin Ling , Zheng, Wei , Gayther, Simon A. , Ramus, Susan J. , Sellers, Thomas A. , Schildkraut, Joellen M. , Phelan, Catherine M., Chenevix‐Trench, Georgia , Cunningham, Julie M. , Ness, Roberta B., Odunsi, Kunle , Goode, Ellen L. , Moysich, Kirsten B., Lu, Karen H. , Lambrechts, Diether , Modugno, Francesmary , Knutson, Keith L. , Hong, Chi‐Chen , Bandera, Elisa V. , Singh, Prashant Kumar , Anton‐Culver, Hoda , Bjørge, Line , Brooks‐Wilson, Angela , Bützow, Ralf C. , Cook, Linda S. , Cramer, Daniel W. , Cybulski, Cezary , Dennis, Joe , Doherty, Jennifer A. , Bois, Andreas du , Dürst, Matthias , Fridley, Brooke L. , Gentry‐Maharaj, Aleksandra , Giles, Graham G. , Glasspool, Rosalind , Gronwald, Jacek , Hildebrandt, Michelle A.T. , Karlan, Beth Y. , Kjær, Susanne K. , Lu, Karen, McLaughlin, John R., Nevanlinna, Heli , Orlow, Irene , Pejovic, Tanja B. , Poole, Elizabeth M. , Risch, Harvey A. , Rudolph, Anja , Shu, Xiao‐Ou , Siddiqui, Nadeem , Tyrer, Jonathan P. , Wentzensen, Nicolas , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Berchuck, Andrew , Pharoah, Paul D.P. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Ramus, Susan J , Teo, Soo H , Tworoger, Shelley S , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Paul, James , Moysich, Kirsten , Lissowska, Jolanta , Campbell, Ian G , Southey, Melissa C , Matsuo, Keitaro , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Zheng, Wei , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Oncotarget | July 6, 2016 | Volume: 7 | Issue: 43 | Pages: 69097-69110
Assessment of Multifactor Gene–Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors
Usset, Joseph , McGuire, Valerie , Sieh, Weiva , Webb, Penelope M. , Chang‐Claude, Jenny, Brinton, Louise A. , Cunningham, Julie M. , DeFazio, Anna , Edwards, Robert P., Gayther, Simon A. , Goodman, Marc T. , Høgdall, Estrid , Jensen, Allan , Johnatty, Sharon E., Lurie, Galina, Massuger, Leon F.A.G. , Menon, Usha , Moysich, Kirsten B. , Ness, Roberta B., Pike, Malcolm C. , Ramus, Susan J. , Rossing, Mary Anne, Rothstein, Joseph H. , Song, Honglin , Thompson, Pamela J., Berg, David J. Van Den, Vierkant, Robert A. , Wang‐Gohrke, Shan , Wentzensen, Nicolas , Whittemore, Alice S. , Wu, Anna H. , Pearce, Celeste Leigh, Schildkraut, Joellen M. , Goode, Ellen L. , Fazio, Anna de , Raghavan, Rama , Tyrer, Jonathan P. , Rudolph, Anja , Anton‐Culver, Hoda , Berchuck, Andrew , Doherty, Jennifer A. , Gentry‐Maharaj, Aleksandra , Kiemeney, Lambertus A. , Kjær, Susanne K. , Larson, Melissa C. , Modugno, Francesmary , Wilkens, Lynne R. , Yang, Hannah , Pharoah, Paul D.P. , Fridley, Brooke L. , Ramus, Susan J , Webb, Penelope M , Jensen, Allan , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten , Sieh, Weiva , Høgdall, Estrid , Goodman, Marc T
Cancer Epidemiology, Biomarkers & Prevention | March 14, 2016 | Volume: 25 | Issue: 5 | Pages: 780-790
Abstract Background: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene–environment interactions related to hormone-related risk factors could differ between obese and non-obese women. Methods: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case–control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. Results: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10−6) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10−5). The most notable obesity–gene–hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10−6). Conclusions: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2. Future work is needed to develop powerful statistical methods able to detect these complex interactions. Impact: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780–90. ©2016 AACR.
Epithelial‐Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk
Amankwah, Ernest K. , Lin, Hui‐Yi , Lawrenson, Kate , Chornokur, Ganna , Aben, Katja K.H. , Antonenkova, Natalia, Bruinsma, Fiona , Bean, Yukie T., Beckmann, Matthias W. , Bisogna, Maria, Bogdanova, Natalia , Brinton, Louise A. , Campbell, Ian , Chen, Zhihua , Chen, Y. Ann , Chang‐Claude, Jenny, Cunningham, Julie M. , Dansonka‐Mieszkowska, Agnieszka , Despierre, Evelyn, Dicks, Ed , Dörk, Thilo , Easton, Douglas F. , Eccles, Diana M., Edwards, Robert P., Ekici, Arif B. , Fasching, Peter A. , Gao, Yu‐Tang , Giles, Graham G. , Glasspool, Rosalind , Goodman, Marc T. , Harrington, Patricia, Harter, Philipp , Hasmad, Hanis Nazihah, Hein, Alexander , Heitz, Florian , Hildebrandt, Michelle A.T., Hillemanns, Peter , Høgdall, Claus , Høgdall, Estrid , Hosono, Satoyo , Iversen, Edwin S., Jakubowska, Anna , Jensen, Allan , Ji, Bu‐Tian , Kellar, Melissa, Kiemeney, Lambertus A. , Krakstad, Camilla , Kupryjańczyk, Jolanta , Lambrechts, Diether , Lambrechts, Sandrina, Le, Nhu D. , Lee, Alice W. , Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A. , Liang, Dong , Lim, Boon Kiong , Lissowska, Jolanta , Lu, Karen, Lubiński, Jan , Lundvall, Lene, Massuger, Leon F.A.G. , Matsuo, Keitaro , McGuire, Valerie , McLaughlin, John R., McNeish, Iain A. , Menon, Usha , Moysich, Kirsten B., Ness, Roberta B., Eilber, Ursula, Odunsi, Kunle , Olson, Sara H. , Orlow, Irene , Oršulić, Sandra , Weber, Rachel Palmieri , Pearce, Celeste Leigh, Pelttari, Liisa M. , Permuth‐Wey, Jennifer, Pike, Malcolm C., Rossing, Mary Anne, Rothstein, Joseph H. , Runnebaum, Ingo B. , Rzepecka, Iwona K. , Salvesen, Helga B., Schernhammer, Eva , Schwaab, Ira, Shu, Xiao‐Ou, Shvetsov, Yurii B. , Sieh, Weiva , Song, Honglin , Southey, Melissa C. , Śpiewankiewicz, Beata, Sucheston‐Campbell, Lara, Teo, Soo‐Hwang , Terry, Kathryn L. , Thompson, Pamela J., Tangen, Ingvild L. , Tworoger, Shelley S. , Altena, Anne M. van , Vierkant, Robert A. , Vergote, Ignace , Walsh, Christine , Wang‐Gohrke, Shan , Wentzensen, Nicolas, Whittemore, Alice S. , Wicklund, Kristine G. , Wu, Anna H. , Wu, Xifeng , Woo, Yin Ling , Zheng, Wei , Kelemen, Linda E. , group, Georgia Chenevix‐Trench on behalf of the AOCS management, Schildkraut, Joellen M. , Ramus, Susan J. , Goode, Ellen L. , Monteiro, Álvaro N.A. , Gayther, Simon A. , Narod, Steven A., Sellers, Thomas A. , Phelan, Catherine M., Lu, Karen H. , Eccles, Diana , Lambrechts, Diether , Tyrer, Jonathan P. , Dennis, Joe , Anton‐Culver, Hoda , Bandera, Elisa V. , Bjørge, Line , Brooks‐Wilson, Angela , Bunker, Clareann H. , Bützow, Ralf C. , Carty, Karen , Cook, Linda S. , Cramer, Daniel W. , Cybulski, Cezary , Bois, Andreas du , Doherty, Jennifer A. , Dürst, Matthias , Eccles, Diana M., Fridley, Brooke L. , Gentry‐Maharaj, Aleksandra , Gronwald, Jacek , Hildebrandt, Michelle A.T. , Karlan, Beth Y. , Jim, Heather , Kjær, Susanne K. , Lu, Karen, McLaughlin, John R., Milne, Roger L. , Modugno, Francesmary , Nevanlinna, Heli , Paul, James , Pejovic, Tanja B. , Poole, Elizabeth M. , Risch, Harvey A. , Rosen, Barry P. , Rudolph, Anja , Siddiqui, Nadeem , Thomsen, Lotte Nedergaard , Wentzensen, Nicolas , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Berchuck, Andrew , group, Georgia Chenevix‐Trench on behalf of the AOCS management, Pharoah, Paul D.P. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Kiemeney, Lambertus A , McNeish, Iain A , Ramus, Susan J , Teo, Soo H , Tworoger, Shelley S , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Monteiro, Alvaro N , Moysich, Kirsten , Orlow, Irene , Lissowska, Jolanta , Campbell, Ian G , Southey, Melissa C , Glasspool, Rosalind , Lin, Hui-Yi , Matsuo, Keitaro , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Bogdanova, Natalia V , Zheng, Wei , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Genetic Epidemiology | September 24, 2015 | Volume: 39 | Issue: 8 | Pages: 689-697
ABSTRACTEpithelial‐mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single‐nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome‐wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT‐related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive‐cancer patients and 23,447 controls. A P‐value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07–1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27–2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27–2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69–0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.