TY - JOUR A1 - Silvestri, Valentina A1 - Barrowdale, Daniel A1 - Mulligan, Anna Marie A1 - Neuhausen, Susan L. A1 - Fox, Stephen A1 - Karlan, Beth Y. A1 - Mitchell, Gillian A1 - James, Paul A1 - Thull, Darcy L. A1 - Zorn, Kristin K. A1 - Carter, Natalie J. A1 - Nathanson, Katherine L. A1 - Domchek, Susan M. A1 - Rebbeck, Timothy R. A1 - Ramus, Susan J. A1 - Nussbaum, Robert L. A1 - Olopade, Olufunmilayo I. A1 - Rantala, Johanna A1 - Yoon, Sook-Yee A1 - Caligo, Maria A. A1 - Spugnesi, Laura A1 - Bojesen, Anders A1 - Pedersen, Inge Sokilde A1 - Thomassen, Mads A1 - Jensen, Uffe Birk A1 - Toland, Amanda Ewart A1 - Senter, Leigha A1 - Andrulis, Irene L. A1 - Glendon, Gord A1 - Hulick, Peter J. A1 - Imyanitov, Evgeny N. A1 - Greene, Mark H. A1 - Mai, Phuong L. A1 - Singer, Christian F. A1 - Rappaport-Fuerhauser, Christine A1 - Kramer, Gero A1 - Vijai, Joseph A1 - Offit, Kenneth A1 - Robson, Mark A1 - Lincoln, Anne A1 - Jacobs, Lauren A1 - Machackova, Eva A1 - Foretova, Lenka A1 - Navratilova, Marie A1 - Vasickova, Petra A1 - Couch, Fergus J. A1 - Hallberg, Emily A1 - Ruddy, Kathryn J. A1 - Sharma, Priyanka A1 - Kim, Sung-Won A1 - Teixeira, Manuel R. A1 - Pinto, Pedro A1 - Montagna, Marco A1 - Matricardi, Laura A1 - Arason, Adalgeir A1 - Johannsson, Oskar Th A1 - Barkardottir, Rosa B. A1 - Jakubowska, Anna A1 - Lubinski, Jan A1 - Izquierdo, Angel A1 - Pujana, Miguel Angel A1 - Balmaña, Judith A1 - Diez, Orland A1 - Ivady, Gabriella A1 - Papp, Janos A1 - Olah, Edith A1 - Kwong, Ava A1 - Nevanlinna, Heli A1 - Aittomäki, Kristiina A1 - Segura, Pedro Perez A1 - Caldes, Trinidad A1 - Van Maerken, Tom A1 - Poppe, Bruce A1 - Claes, Kathleen B. M. A1 - Isaacs, Claudine A1 - Elan, Camille A1 - Lasset, Christine A1 - Stoppa-Lyonnet, Dominique A1 - Barjhoux, Laure A1 - Belotti, Muriel A1 - Meindl, Alfons A1 - Gehrig, Andrea A1 - Sutter, Christian A1 - Engel, Christoph A1 - Niederacher, Dieter A1 - Steinemann, Doris A1 - Hahnen, Eric A1 - Kast, Karin A1 - Arnold, Norbert A1 - Varon-Mateeva, Raymonda A1 - Wand, Dorothea A1 - Godwin, Andrew K. A1 - Evans, D. Gareth A1 - Frost, Debra A1 - Perkins, Jo A1 - Adlard, Julian A1 - Izatt, Louise A1 - Platte, Radka A1 - Eeles, Ros A1 - Ellis, Steve A1 - Hamann, Ute A1 - Garber, Judy A1 - Fostira, Florentia A1 - Fountzilas, George A1 - Pasini, Barbara A1 - Giannini, Giuseppe A1 - Rizzolo, Piera A1 - Russo, Antonio A1 - Cortesi, Laura A1 - Papi, Laura A1 - Varesco, Liliana A1 - Palli, Domenico A1 - Zanna, Ines A1 - Savarese, Antonella A1 - Radice, Paolo A1 - Manoukian, Siranoush A1 - Peissel, Bernard A1 - Barile, Monica A1 - Bonanni, Bernardo A1 - Viel, Alessandra A1 - Pensotti, Valeria A1 - Tommasi, Stefania A1 - Peterlongo, Paolo A1 - Weitzel, Jeffrey N. A1 - Osorio, Ana A1 - Benitez, Javier A1 - McGuffog, Lesley A1 - Healey, Sue A1 - Gerdes, Anne-Marie A1 - Ejlertsen, Bent A1 - Hansen, Thomas V. O. A1 - Steele, Linda A1 - Ding, Yuan Chun A1 - Tung, Nadine A1 - Janavicius, Ramunas A1 - Goldgar, David E. A1 - Buys, Saundra S. A1 - Daly, Mary B. A1 - Bane, Anita A1 - Terry, Mary Beth A1 - John, Esther M. A1 - Southey, Melissa A1 - Easton, Douglas F. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. A1 - Ottini, Laura T1 - Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2 JF - Breast Cancer Research N2 - Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management. KW - Male breast cancer KW - BRCA1/2 KW - Pathology KW - Histologic grade KW - Genotype–phenotype correlations Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164769 VL - 18 IS - 15 ER - TY - JOUR A1 - Vigorito, Elena A1 - Kuchenbaecker, Karoline B. A1 - Beesley, Jonathan A1 - Adlard, Julian A1 - Agnarsson, Bjarni A. A1 - Andrulis, Irene L. A1 - Arun, Banu K. A1 - Barjhoux, Laure A1 - Belotti, Muriel A1 - Benitez, Javier A1 - Berger, Andreas A1 - Bojesen, Anders A1 - Bonanni, Bernardo A1 - Brewer, Carole A1 - Caldes, Trinidad A1 - Caligo, Maria A. A1 - Campbell, Ian A1 - Chan, Salina B. A1 - Claes, Kathleen B. M. A1 - Cohn, David E. A1 - Cook, Jackie A1 - Daly, Mary B. A1 - Damiola, Francesca A1 - Davidson, Rosemarie A1 - de Pauw, Antoine A1 - Delnatte, Capucine A1 - Diez, Orland A1 - Domchek, Susan M. A1 - Dumont, Martine A1 - Durda, Katarzyna A1 - Dworniczak, Bernd A1 - Easton, Douglas F. A1 - Eccles, Diana A1 - Ardnor, Christina Edwinsdotter A1 - Eeles, Ros A1 - Ejlertsen, Bent A1 - Ellis, Steve A1 - Evans, D. Gareth A1 - Feliubadalo, Lidia A1 - Fostira, Florentia A1 - Foulkes, William D. A1 - Friedman, Eitan A1 - Frost, Debra A1 - Gaddam, Pragna A1 - Ganz, Patricia A. A1 - Garber, Judy A1 - Garcia-Barberan, Vanesa A1 - Gauthier-Villars, Marion A1 - Gehrig, Andrea A1 - Gerdes, Anne-Marie A1 - Giraud, Sophie A1 - Godwin, Andrew K. A1 - Goldgar, David E. A1 - Hake, Christopher R. A1 - Hansen, Thomas V. O. A1 - Healey, Sue A1 - Hodgson, Shirley A1 - Hogervorst, Frans B. L. A1 - Houdayer, Claude A1 - Hulick, Peter J. A1 - Imyanitov, Evgeny N. A1 - Isaacs, Claudine A1 - Izatt, Louise A1 - Izquierdo, Angel A1 - Jacobs, Lauren A1 - Jakubowska, Anna A1 - Janavicius, Ramunas A1 - Jaworska-Bieniek, Katarzyna A1 - Jensen, Uffe Birk A1 - John, Esther M. A1 - Vijai, Joseph A1 - Karlan, Beth Y. A1 - Kast, Karin A1 - Khan, Sofia A1 - Kwong, Ava A1 - Laitman, Yael A1 - Lester, Jenny A1 - Lesueur, Fabienne A1 - Liljegren, Annelie A1 - Lubinski, Jan A1 - Mai, Phuong L. A1 - Manoukian, Siranoush A1 - Mazoyer, Sylvie A1 - Meindl, Alfons A1 - Mensenkamp, Arjen R. A1 - Montagna, Marco A1 - Nathanson, Katherine L. A1 - Neuhausen, Susan L. A1 - Nevanlinna, Heli A1 - Niederacher, Dieter A1 - Olah, Edith A1 - Olopade, Olufunmilayo I. A1 - Ong, Kai-ren A1 - Osorio, Ana A1 - Park, Sue Kyung A1 - Paulsson-Karlsson, Ylva A1 - Pedersen, Inge Sokilde A1 - Peissel, Bernard A1 - Peterlongo, Paolo A1 - Pfeiler, Georg A1 - Phelan, Catherine M. A1 - Piedmonte, Marion A1 - Poppe, Bruce A1 - Pujana, Miquel Angel A1 - Radice, Paolo A1 - Rennert, Gad A1 - Rodriguez, Gustavo C. A1 - Rookus, Matti A. A1 - Ross, Eric A. A1 - Schmutzler, Rita Katharina A1 - Simard, Jacques A1 - Singer, Christian F. A1 - Slavin, Thomas P. A1 - Soucy, Penny A1 - Southey, Melissa A1 - Steinemann, Doris A1 - Stoppa-Lyonnet, Dominique A1 - Sukiennicki, Grzegorz A1 - Sutter, Christian A1 - Szabo, Csilla I. A1 - Tea, Muy-Kheng A1 - Teixeira, Manuel R. A1 - Teo, Soo-Hwang A1 - Terry, Mary Beth A1 - Thomassen, Mads A1 - Tibiletti, Maria Grazia A1 - Tihomirova, Laima A1 - Tognazzo, Silvia A1 - van Rensburg, Elizabeth J. A1 - Varesco, Liliana A1 - Varon-Mateeva, Raymonda A1 - Vratimos, Athanassios A1 - Weitzel, Jeffrey N. A1 - McGuffog, Lesley A1 - Kirk, Judy A1 - Toland, Amanda Ewart A1 - Hamann, Ute A1 - Lindor, Noralane A1 - Ramus, Susan J. A1 - Greene, Mark H. A1 - Couch, Fergus J. A1 - Offit, Kenneth A1 - Pharoah, Paul D. P. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. T1 - Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers JF - PLoS ONE N2 - Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. KW - fine-scale mapping KW - ovarian cancer KW - genetics KW - BRCA1 KW - BRCA2 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166869 VL - 11 IS - 7 ER -