Citations 5
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.
Novel Common Genetic Susceptibility Loci for Colorectal Cancer
Schmit, Stephanie L. , Edlund, Christopher K., Schumacher, Fredrick R. , Harrison, Tabitha A. , Huyghe, Jeroen R. , Qu, Chenxu, Melas, Marilena , Berg, David Van Den , Wang, Hansong, Tring, Stephanie, Plummer, Sarah J. , Alonso, M. Henar , Anton, Kristen , Aragaki, Aaron K. , Arndt, Volker , Barry, Elizabeth L. , Berndt, Sonja I. , Bloomer, Amanda M. , Boehm, Juergen , Brenner, Hermann , Brezina, Stefanie , Buchanan, Daniel D. , Butterbach, Katja, Caan, Bette J. , Carlson, Christopher S. , Castelao, Jose E. , Chang‐Claude, Jenny , Cheng, Ya‐Wen , Chin, Lee Soo, Church, Timothy R. , Correa, Marcia Cruz, Curtis, Keith R. , Duggan, David , Easton, Douglas F. , English, Dallas R. , Fischer, Rocky, Fritsche, Lars G. , Fuchs, Charles S. , Gago-Domínguez, Manuela , Gala, Manish , Gallinger, Steven , Gauderman, W. James, Giovannucci, Edward L. , Gogarten, Stephanie M. , González‐Villalpando, Clicerio, Gonzalez-Villalpando, Elena M., Greenson, Joel K. , Gsur, Andrea , Gunter, Marc J. , Haiman, Christopher A. , Hampe, Jochen , Harlid, Sophia , Harju, John F., Hayes, Richard B. , Hofer, Philipp , Hoffmeister, Michael , Huang, Shu-Chen, Huerta, José María , Hunter, David J., Idos, Gregory , Jackson, Rebecca D. , Jacobs, Eric J. , Jee, Sun Ha , Jenkins, Mark A. , Jia, Wei-Hua , Jiao, Shuo , Joshi, Amit D. , Kolonel, Laurence N. , Kono, Suminori , Krogh, Vittorio , Küehn, Tilman, Küry, Sébastien , LaCroix, Andrea Z. , Laurie, Cecelia , Lejbkowicz, Flavio, Lemire, Mathieu , Lenz, Heinz‐Josef , Levine, David , Li, Li , Lindor, Noralane M. , Liu, Yun-Ru, Lu, Yingchang , Luh, Frank , Ma, Jing , Mancao, Christoph , Manion, Frank J. , Markowitz, Sanford D. , Martín, Vicente , Matsuo, Keitaro , McDonnell, Kevin , McNeil, Caroline E, Murphy, Neil , Offit, Kenneth, Omichessan, Hanane , Cotoré, Jesús Paredes, Pérez‐Mayoral, Julyann, Rennert, Gad , Rennert, Hedy S., Riggs, Bridget M., Schafmayer, Clemens, Sellers, Thomas A. , Seminara, Daniela, Shibata, David , Siegel, Erin M. , Slattery, Martha L. , Stintzing, Sebastian , Taverna, Darin, Thibodeau, Stephen N. , Thomas, Duncan C. , Trichopoulou, Antonia , Duijnhoven, Fränzel J.B. van , Guelpan, Bethany van, Virtamo, Jarmo, Weinstein, Stephanie J. , Win, Aung Ko , Woods, Michael O. , Wu, Anna H. , Wu, Kana , Xiang, Yong-Bing , Zanke, Brent W., Zeng, Yi-Xin , Zhang, Ben , Zubair, Niha, Figueiredo, Jane C. , Lindblom, Annika , Moreno, Vı́ctor , Peters, Ulrike , Conti, David V. , Gruber, Stephen B. , Kühn, Tilman , Buchanan, Daniel D , Win, Aung K , Rennert, Gad , Hoffmeister, Michael , Arndt, Volker , English, Dallas R , Martín, Vicente , Moreno, Victor , Gunter, Marc J , Jenkins, Mark A , Van Den Berg, David J , Harrison, Tabitha A , Matsuo, Keitaro , Kury, Sebastien , Brenner, Hermann , Gago-Dominguez, Manuela , Hampe, Jochen , Murphy, Neil , Hayes, Richard B , Brezina, Stefanie , Conti, David V , Gong, Jian Feng , Albanes, Demetrius , Amos, Christopher I. , Bezieau, Stéphane , Bien, Stephanie A. , Boutron‐Ruault, Marie‐Christine , Campbell, Peter T. , Chan, Andrew T. , Chanock, Stephen Jacob , Cheng, Iona C. , Church, James M. , Coetzee, Gerhard A. , Cotterchio, Michelle , Feskens, Edith J. M. , FitzGerald, Liesel M. , Fortini, Barbara K. , Giles, Graham G. , Grady, William M. , Hopper, John L. , Hudson, Thomas J , Iwasaki, Motoki , Kooperberg, Charles , Li, Christopher I , Lieb, Wolfgang , Lin, Yi , Liu, Yun‐Ru , Loupakis, Fotios , Matsuda, Koichi , McNeil, Caroline E, Milne, Roger L. , Molina, Antonio José , Mukherjee, Bhramar , Newcomb, Polly A. , Palli, Domenico , Pharoah, Paul D.P. , Potter, John D. , Qu, Conghui , Raskin, Leon , Schoen, Robert E. , Severi, Gianluca , Shi, Wei , Shu, Xiao‐Ou , Southey, Melissa C. , Stadler, Zsofia , Stern, Mariana Carla , Tsugane, Shoichiro , Ulrich, Cornelia M. , Vijai, Joseph , White, Emily E. , Wolk, Alicja , Yen, Yun , Kweon, Sun-Seog , Zheng, Wei , Marchand, Loı̈c Le , Casey, Graham , Church, Timothy R , Caan, Bette J , Lindblom, Annika
JNCI: Journal of the National Cancer Institute | April 30, 2018 | Volume: 111 | Issue: 2 | Pages: 146-157
Abstract Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11
Siddiq, Afshan , Chen, Gary K., Lindström, Sara, Eccles, Diana , Millikan, Robert C., Michailidou, Kyriaki , Beckmann, Lars , Aittomäki, Kristiina , Apicella, Carmel, Investigators, Australian Breast Cancer Tissue Bank, Baglietto, Laura , Bandera, Elisa V. , Beckmann, Matthias W. , Berg, Christine D. , Blomqvist, Carl , Brauch, Hiltrud , Brinton, Louise A. , Bui, Minh , Buring, Julie E. , Campa, Daniele , Carpenter, Jane, Chang‐Claude, Jenny, Chen, Constance, Clavel-Chapelon, Françoise, Cox, Angela , Cross, Simon S. , Czene, Kamila , Deming, Sandra L., Diasio, Robert B. , Diver, W. Ryan , Dunning, Alison M. , Durcan, Lorraine , Ekici, Arif B. , Fasching, Peter A. , Study, Familial Breast Cancer, Fejerman, Laura , Figueroa, Jonine D. , Flesch‐Janys, Dieter, Gaudet, Mia M., Gerty, Susan M. , Rodriguez‐Gil, Jorge L. , Giles, Graham G. , Gils, Carla H. van , Graham, Nikki , Greco, Dario , Hankinson, Susan E. , Hartmann, Arndt, Hein, Rebecca, Heinz, Judith , Hoover, Robert N. , Hu, Jennifer J. , Huntsman, Scott , Irwanto, Astrid , Jacobs, Kevin B. , John, Esther M. , Justenhoven, Christina , Kolonel, Laurence N. , Coetzee, Gerhard A. , Lathrop, Mark, Lee, I‐Min , Lesnick, Timothy G. , Lichtner, Peter , Liu, Jianjun , Lund, Eiliv , Makalic, Enes , Martin, Nicholas G. , McLean, Catriona , Meijers‐Heijboer, Hanne , Meindl, Alfons , Miron, Penelope , Montgomery, Grant W. , Müller‐Myhsok, Bertram , Nickels, Stefan , Nyante, Sarah J. , Olswold, Curtis, Overvad, Kim , Palli, Domenico , Park, Daniel J. , Palmer, Julie R. , Peto, Julian , Rahman, Nazneen , Rivadeneira, Fernando , Schmutzler, Rita K. , Slager, Susan, Southey, Melissa C. , Stevens, Kristen N., Sinn, Hans‐Peter , Ross, Eric A. , Ríboli, Elio , Schumacher, Fredrick R. , Severi, Gianluca , Stone, Jennifer , Sund, Malin , Tapper, William , Thun, Michael J., Travis, Ruth C. , Turnbull, Clare , Uitterlinden, André G. , Waisfisz, Quinten , Wang, Zhaoming , Weaver, JoEllen , Schulz-Wendtland, Rüdiger, Nevanlinna, Heli , Easton, Douglas F., Hunter, David J. , Henderson, Brian E., García‐Closas, Montserrat , Kraft, Peter , Haiman, Christopher A. , Vachon, Celine M. , Zheng, Wei , Purrington, Kristen S. , Couch, Fergus J. , Stram, Daniel O. , Rhie, Suhn K. , Ambrosone, Christine B. , Amiano, Pilar , Investigators, Australian Breast Cancer Tissue Bank, Bernstein, Leslie , Bui, Minh , Buys, Saundra S. , Chasman, Daniel I. , Study, Familial Breast Cancer, Feigelson, Heather Spencer , Fletcher, Olivia , Godwin, Andrew K. , Hall, Per N , Hankinson, Susan E. , Hopper, John L. , Ingles, Sue A. , Isaacs, Claudine , Kaaks, Rudolf , Marchand, Loı̈c Le , Lee, Adam M. , Meindl, Alfons , Monroe, Kristine R. , Pathak, Harsh B. , Pharoah, Paul D.P. , Schmidt, Daniel F. , Press, Michael F. , Ridker, Paul M. , dos‐Santos‐Silva, Isabel , Wang, Xianshu , Wilkens, Lynne R. , Berg, David Van Den , Zheng, Wei , Ziegler, Regina G. , Ziv, Elad , Chanock, Stephen Jacob , Vachon, Celine M. , Nevanlinna, H , Giles, Graham G , Eccles, Diana , John, Esther M , Palli, Domenico , Southey, Melissa C , Martin, Nicholas G , Sinn, Peter , Travis, Ruth C , Wang, Zhaoming , Dunning, Alison M , Cox, Angela , García-Closas, Montserrat , Severi, Gianluca , Makalic, Enes , Ekici, Arif B , Michailidou, Kyriaki , Palmer, Julie R , Kraft, Peter , Zheng, Wei , Figueroa, Jonine D , Nyante, Sarah , Czene, Kamila , Stone, Jennifer , Riboli, Elio , Sund, Malin , Baglietto, Laura , Purrington, Kristen S , Mclean, Catriona , Brauch, Hiltrud , Liu, Jing , Bandera, Elisa V.
Human Molecular Genetics | September 14, 2012 | Volume: 21 | Issue: 24 | Pages: 5373-5384