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2. Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families

Author

Kiat-Tee Tan, Benita, Tan, Su-Ming, Mien Tan, Veronique Kiak, Tan, Ern Yu, Lim, Geok Hoon, Khng, Alexis, Ch’ng, Gaik-Siew, Omar, Jamil, Yong, Chee-Meng, Aliyas, Ismail, Malik, Rozita Abdul, Subramaniam, Suguna, Sim, Wee-Wee, Lim, Chun Sen, Lee, Saw-Joo, Lim, Keng-Joo, Shafiee, Mohamad Nasir, Ismail, Fuad Ismail, Ismail, Mohd Pazudin, Mohamed Jamli, Mohamad Faiz, Kumarasamy, Suresh, Low, John S.H., Ahmad Mustafa, Ahmad Muzamir, Makanjang, Mary J., Taib, Shahila, Cheah, Nellie, Fong, Chee-Kin, Ho, Kean-Fatt, Deniel, Azura, Ang, Soo Fan, Ahmad Badruddin, Ahmad Radzi, Tho, Lye-Mun, Ho, Weang-Kee, Hassan, Nur Tiara, Yoon, Sook-Yee, Yang, Xin, Lim, Joanna M.C., Binte Ishak, Nur Diana, Ho, Peh Joo, Wijaya, Eldarina A., Ng, Patsy Pei-Sze, Luccarini, Craig, Allen, Jamie, Tai, Mei-Chee, Chiang, Jianbang, Zhang, Zewen, See, Mee-Hoong, Thong, Meow-Keong, Woo, Yin-Ling, Dunning, Alison M., Hartman, Mikael, Yip, Cheng-Har, Mohd Taib, Nur Aishah, Easton, Douglas F., Li, Jingmei, Ngeow, Joanne, Antoniou, Antonis C., and Teo, Soo-Hwang

Published
2024
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6. The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer

Author

Reid, Frances, primary, Adams, Tracey, additional, Adel, Rafe Sadnan, additional, Andrade, Carlos E., additional, Bajwa, Anmol, additional, Bambury, Ian G., additional, Benhima, Nada, additional, Bolatbekova, Raikhan, additional, Leon, David Cantu-De, additional, Charlton, Phaedra, additional, Chirinos, Carlos Chávez, additional, Cohen, Robin, additional, Eiken, Mary, additional, Estrada, Erick Estuardo, additional, Kaidarova, Dilyara, additional, Lau, Iren, additional, MacKay, Clara, additional, Makondi, Precious Takondwa, additional, Mukhopadhyay, Asima, additional, Mustapha, Aisha, additional, Noll, Florencia, additional, Origa, Martin, additional, Pariyar, Jitendra, additional, Pervin, Shahana, additional, Phan, Ngoc T. H., additional, Refky, Basel, additional, Shaffi, Afrin F., additional, Strömsholm, Eva-Maria, additional, Woo, Yin Ling, additional, Yoon, Sook-Yee, additional, Zakirova, Nargiza, additional, Chidebe, Runcie C. W., additional, Funston, Garth, additional, and Soerjomataram, Isabelle, additional

Published
2024
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7. Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families

Author

Ho, Weang-Kee, primary, Hassan, Nur Tiara, additional, Yoon, Sook-Yee, additional, Yang, Xin, additional, Lim, Joanna M.C., additional, Binte Ishak, Nur Diana, additional, Ho, Peh Joo, additional, Wijaya, Eldarina A., additional, Ng, Patsy Pei-Sze, additional, Luccarini, Craig, additional, Allen, Jamie, additional, Tai, Mei-Chee, additional, Chiang, Jianbang, additional, Zhang, Zewen, additional, See, Mee-Hoong, additional, Thong, Meow-Keong, additional, Woo, Yin-Ling, additional, Dunning, Alison M., additional, Hartman, Mikael, additional, Yip, Cheng-Har, additional, Mohd Taib, Nur Aishah, additional, Easton, Douglas F., additional, Li, Jingmei, additional, Ngeow, Joanne, additional, Antoniou, Antonis C., additional, Teo, Soo-Hwang, additional, Kiat-Tee Tan, Benita, additional, Tan, Su-Ming, additional, Mien Tan, Veronique Kiak, additional, Tan, Ern Yu, additional, Lim, Geok Hoon, additional, Khng, Alexis, additional, Ch’ng, Gaik-Siew, additional, Omar, Jamil, additional, Yong, Chee-Meng, additional, Aliyas, Ismail, additional, Malik, Rozita Abdul, additional, Subramaniam, Suguna, additional, Sim, Wee-Wee, additional, Lim, Chun Sen, additional, Lee, Saw-Joo, additional, Lim, Keng-Joo, additional, Shafiee, Mohamad Nasir, additional, Ismail, Fuad Ismail, additional, Ismail, Mohd Pazudin, additional, Mohamed Jamli, Mohamad Faiz, additional, Kumarasamy, Suresh, additional, Low, John S.H., additional, Ahmad Mustafa, Ahmad Muzamir, additional, Makanjang, Mary J., additional, Taib, Shahila, additional, Cheah, Nellie, additional, Fong, Chee-Kin, additional, Ho, Kean-Fatt, additional, Deniel, Azura, additional, Ang, Soo Fan, additional, Ahmad Badruddin, Ahmad Radzi, additional, and Tho, Lye-Mun, additional

Published
2024
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8. Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Author

Silvestri, Valentina, Barrowdale, Daniel, Mulligan, Anna Marie, Neuhausen, Susan L, Fox, Stephen, Karlan, Beth Y, Mitchell, Gillian, James, Paul, Thull, Darcy L, Zorn, Kristin K, Carter, Natalie J, Nathanson, Katherine L, Domchek, Susan M, Rebbeck, Timothy R, Ramus, Susan J, Nussbaum, Robert L, Olopade, Olufunmilayo I, Rantala, Johanna, Yoon, Sook-Yee, Caligo, Maria A, Spugnesi, Laura, Bojesen, Anders, Pedersen, Inge Sokilde, Thomassen, Mads, Jensen, Uffe Birk, Toland, Amanda Ewart, Senter, Leigha, Andrulis, Irene L, Glendon, Gord, Hulick, Peter J, Imyanitov, Evgeny N, Greene, Mark H, Mai, Phuong L, Singer, Christian F, Rappaport-Fuerhauser, Christine, Kramer, Gero, Vijai, Joseph, Offit, Kenneth, Robson, Mark, Lincoln, Anne, Jacobs, Lauren, Machackova, Eva, Foretova, Lenka, Navratilova, Marie, Vasickova, Petra, Couch, Fergus J, Hallberg, Emily, Ruddy, Kathryn J, Sharma, Priyanka, Kim, Sung-Won, kConFab Investigators, Teixeira, Manuel R, Pinto, Pedro, Montagna, Marco, Matricardi, Laura, Arason, Adalgeir, Johannsson, Oskar Th, Barkardottir, Rosa B, Jakubowska, Anna, Lubinski, Jan, Izquierdo, Angel, Pujana, Miguel Angel, Balmaña, Judith, Diez, Orland, Ivady, Gabriella, Papp, Janos, Olah, Edith, Kwong, Ava, Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Nevanlinna, Heli, Aittomäki, Kristiina, Perez Segura, Pedro, Caldes, Trinidad, Van Maerken, Tom, Poppe, Bruce, Claes, Kathleen BM, Isaacs, Claudine, Elan, Camille, Lasset, Christine, Stoppa-Lyonnet, Dominique, Barjhoux, Laure, Belotti, Muriel, Meindl, Alfons, Gehrig, Andrea, Sutter, Christian, Engel, Christoph, Niederacher, Dieter, Steinemann, Doris, Hahnen, Eric, Kast, Karin, Arnold, Norbert, Varon-Mateeva, Raymonda, Wand, Dorothea, Godwin, Andrew K, Evans, D Gareth, Frost, Debra, Perkins, Jo, Adlard, Julian, Izatt, Louise, and Platte, Radka

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Breast Neoplasms, Male, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Polymorphism, Single Nucleotide, Male breast cancer, BRCA1/2, Pathology, Histologic grade, Genotype-phenotype correlations, kConFab Investigators, Hereditary Breast and Ovarian Cancer Research Group Netherlands, EMBRACE, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundBRCA1 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).MethodsWe 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.ResultsAmong 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)).ConclusionsOn 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.

Published
2016

9. The Global State of the Genetic Counseling Profession

Author

Abacan, MaryAnn, Alsubaie, Lamia, Barlow-Stewart, Kristine, Caanen, Beppy, Cordier, Christophe, Courtney, Eliza, Davoine, Emeline, Edwards, Janice, Elackatt, Niby J., Gardiner, Kate, Guan, Yue, Huang, Lian-Hua, Malmgren, Charlotta Ingvoldstad, Kejriwal, Sahil, Kim, Hyon J., Lambert, Deborah, Lantigua-Cruz, Paulina Araceli, Lee, Juliana M. H., Lodahl, Marianne, Lunde, Åshild, Macaulay, Shelley, Macciocca, Ivan, Margarit, Sonia, Middleton, Anna, Moldovan, Ramona, Ngeow, Joanne, Obregon-Tito, Alexandra J., Ormond, Kelly E., Paneque, Milena, Powell, Karen, Sanghavi, Kunal, Scotcher, Diana, Scott, Jenna, Juhé, Clara Serra, Shkedi-Rafid, Shiri, Wessels, Tina-Marié, Yoon, Sook-Yee, and Wicklund, Catherine

Published
2019
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10. European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

Author

Ho, Weang-Kee, Tan, Min-Min, Mavaddat, Nasim, Tai, Mei-Chee, Mariapun, Shivaani, Li, Jingmei, Ho, Peh-Joo, Dennis, Joe, Tyrer, Jonathan P., Bolla, Manjeet K., Michailidou, Kyriaki, Wang, Qin, Kang, Daehee, Choi, Ji-Yeob, Jamaris, Suniza, Shu, Xiao-Ou, Yoon, Sook-Yee, Park, Sue K., Kim, Sung-Won, Shen, Chen-Yang, Yu, Jyh-Cherng, Tan, Ern Yu, Chan, Patrick Mun Yew, Muir, Kenneth, Lophatananon, Artitaya, Wu, Anna H., Stram, Daniel O., Matsuo, Keitaro, Ito, Hidemi, Chan, Ching Wan, Ngeow, Joanne, Yong, Wei Sean, Lim, Swee Ho, Lim, Geok Hoon, Kwong, Ava, Chan, Tsun L., Tan, Su Ming, Seah, Jaime, John, Esther M., Kurian, Allison W., Koh, Woon-Puay, Khor, Chiea Chuen, Iwasaki, Motoki, Yamaji, Taiki, Tan, Kiak Mien Veronique, Tan, Kiat Tee Benita, Spinelli, John J., Aronson, Kristan J., Hasan, Siti Norhidayu, Rahmat, Kartini, Vijayananthan, Anushya, Sim, Xueling, Pharoah, Paul D. P., Zheng, Wei, Dunning, Alison M., Simard, Jacques, van Dam, Rob Martinus, Yip, Cheng-Har, Taib, Nur Aishah Mohd, Hartman, Mikael, Easton, Douglas F., Teo, Soo-Hwang, and Antoniou, Antonis C.

Published
2020
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12. Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort

Author

Padmanabhan, Heamanthaa, primary, Mariapun, Shivaani, additional, Lee, Sheau‐Yee, additional, Hassan, Nur Tiara, additional, Lee, Daphne Shin‐Chi, additional, Meiser, Bettina, additional, Wong, Siu‐Wan, additional, Lee, Yong‐Quan, additional, Yip, Cheng‐Har, additional, Teo, Soo‐Hwang, additional, Thong, Meow‐Keong, additional, Taib, Nur Aishah Mohd, additional, and Yoon, Sook‐Yee, additional

Published
2022
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13. BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

Author

Meeks, Huong D., Song, Honglin, Michailidou, Kyriaki, Bolla, Manjeet K., Dennis, Joe, Wang, Qin, Barrowdale, Daniel, Frost, Debra, McGuffog, Lesley, Ellis, Steve, Feng, Bingjian, Buys, Saundra S., Hopper, John L., Southey, Melissa C., Tesoriero, Andrea, James, Paul A., Bruinsma, Fiona, Campbell, Ian G., Broeks, Annegien, Schmidt, Marjanka K., Hogervorst, Frans B. L., Beckman, Matthias W., Fasching, Peter A., Fletcher, Olivia, Johnson, Nichola, Sawyer, Elinor J., Riboli, Elio, Banerjee, Susana, Menon, Usha, Tomlinson, Ian, Burwinkel, Barbara, Hamann, Ute, Marme, Frederik, Rudolph, Anja, Janavicius, Ramunas, Tihomirova, Laima, Tung, Nadine, Garber, Judy, Cramer, Daniel, Terry, Kathryn L., Poole, Elizabeth M., Tworoger, Shelley S., Dorfling, Cecilia M., van Rensburg, Elizabeth J., Godwin, Andrew K., Guénel, Pascal, Truong, Thérèse, Stoppa-Lyonnet, Dominique, Damiola, Francesca, Mazoyer, Sylvie, Sinilnikova, Olga M., Isaacs, Claudine, Maugard, Christine, Bojesen, Stig E., Flyger, Henrik, Gerdes, Anne-Marie, Hansen, Thomas V. O., Jensen, Allen, Kjaer, Susanne K., Hogdall, Claus, Hogdall, Estrid, Pedersen, Inge Sokilde, Thomassen, Mads, Benitez, Javier, González-Neira, Anna, Osorio, Ana, Hoya, Miguel de la, Segura, Pedro Perez, Diez, Orland, Lazaro, Conxi, Brunet, Joan, Anton-Culver, Hoda, Eunjung, Lee, John, Esther M., Neuhausen, Susan L., Ding, Yuan Chun, Castillo, Danielle, Weitzel, Jeffrey N., Ganz, Patricia A., Nussbaum, Robert L., Chan, Salina B., Karlan, Beth Y., Lester, Jenny, Wu, Anna, Gayther, Simon, Ramus, Susan J., Sieh, Weiva, Whittermore, Alice S., Monteiro, Alvaro N. A., Phelan, Catherine M., Terry, Mary Beth, Piedmonte, Marion, Offit, Kenneth, Robson, Mark, Levine, Douglas, Moysich, Kirsten B., Cannioto, Rikki, Olson, Sara H., Daly, Mary B., Nathanson, Katherine L., Domchek, Susan M., Lu, Karen H., Liang, Dong, Hildebrant, Michelle A. T., Ness, Roberta, Modugno, Francesmary, Pearce, Leigh, Goodman, Marc T., Thompson, Pamela J., Brenner, Hermann, Butterbach, Katja, Meindl, Alfons, Hahnen, Eric, Wappenschmidt, Barbara, Brauch, Hiltrud, Brüning, Thomas, Blomqvist, Carl, Khan, Sofia, Nevanlinna, Heli, Pelttari, Liisa M., Aittomäki, Kristiina, Butzow, Ralf, Bogdanova, Natalia V., Dörk, Thilo, Lindblom, Annika, Margolin, Sara, Rantala, Johanna, Kosma, Veli-Matti, Mannermaa, Arto, Lambrechts, Diether, Neven, Patrick, Claes, Kathleen B. M., Maerken, Tom Van, Chang-Claude, Jenny, Flesch-Janys, Dieter, Heitz, Florian, Varon-Mateeva, Raymonda, Peterlongo, Paolo, Radice, Paolo, Viel, Alessandra, Barile, Monica, Peissel, Bernard, Manoukian, Siranoush, Montagna, Marco, Oliani, Cristina, Peixoto, Ana, Teixeira, Manuel R., Collavoli, Anita, Hallberg, Emily, Olson, Janet E., Goode, Ellen L., Hart, Steven N., Shimelis, Hermela, Cunningham, Julie M., Giles, Graham G., Milne, Roger L., Healey, Sue, Tucker, Kathy, Haiman, Christopher A., Henderson, Brian E., Goldberg, Mark S., Tischkowitz, Marc, Simard, Jacques, Soucy, Penny, Eccles, Diana M., Le, Nhu, Borresen-Dale, Anne-Lise, Kristensen, Vessela, Salvesen, Helga B., Bjorge, Line, Bandera, Elisa V., Risch, Harvey, Zheng, Wei, Beeghly-Fadiel, Alicia, Cai, Hui, Pylkäs, Katri, Tollenaar, Robert A. E. M., Ouweland, Ans M. W. van der, Andrulis, Irene L., Knight, Julia A., Narod, Steven, Devilee, Peter, Winqvist, Robert, Figueroa, Jonine, Greene, Mark H., Mai, Phuong L., Loud, Jennifer T., García-Closas, Montserrat, Schoemaker, Minouk J., Czene, Kamila, Darabi, Hatef, McNeish, Iain, Siddiquil, Nadeem, Glasspool, Rosalind, Kwong, Ava, Park, Sue K., Teo, Soo Hwang, Yoon, Sook-Yee, Matsuo, Keitaro, Hosono, Satoyo, Woo, Yin Ling, Gao, Yu-Tang, Foretova, Lenka, Singer, Christian F., Rappaport-Feurhauser, Christine, Friedman, Eitan, Laitman, Yael, Rennert, Gad, Imyanitov, Evgeny N., Hulick, Peter J., Olopade, Olufunmilayo I., Senter, Leigha, Olah, Edith, Doherty, Jennifer A., Schildkraut, Joellen, Koppert, Linetta B., Kiemeney, Lambertus A., Massuger, Leon F. A. G., Cook, Linda S., Pejovic, Tanja, Li, Jingmei, Borg, Ake, Öfverholm, Anna, Rossing, Mary Anne, Wentzensen, Nicolas, Henriksson, Karin, Cox, Angela, Cross, Simon S., Pasini, Barbara J., Shah, Mitul, Kabisch, Maria, Torres, Diana, Jakubowska, Anna, Lubinski, Jan, Gronwald, Jacek, Agnarsson, Bjarni A., Kupryjanczyk, Jolanta, Moes-Sosnowska, Joanna, Fostira, Florentia, Konstantopoulou, Irene, Slager, Susan, Jones, Michael, Antoniou, Antonis C., Berchuck, Andrew, Swerdlow, Anthony, Chenevix-Trench, Georgia, Dunning, Alison M., Pharoah, Paul D. P., Hall, Per, Easton, Douglas F., Couch, Fergus J., Spurdle, Amanda B., and Goldgar, David E.

Published
2016
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14. Predicting the Likelihood of Carrying a BRCA1 or BRCA2 Mutation in Asian Patients With Breast Cancer

Author

Ang, Boon Hong, primary, Ho, Weang Kee, additional, Wijaya, Eldarina, additional, Kwan, Pui Yoke, additional, Ng, Pei Sze, additional, Yoon, Sook Yee, additional, Hasan, Siti Norhidayu, additional, Lim, Joanna M.C., additional, Hassan, Tiara, additional, Tai, Mei-Chee, additional, Allen, Jamie, additional, Lee, Andrew, additional, Taib, Nur Aishah Mohd, additional, Yip, Cheng Har, additional, Hartman, Mikael, additional, Lim, Swee Ho, additional, Tan, Ern Yu, additional, Tan, Benita K.T., additional, Tan, Su-Ming, additional, Tan, Veronique K.M., additional, Ho, Peh Joo, additional, Khng, Alexis J., additional, Dunning, Alison M., additional, Li, Jingmei, additional, Easton, Douglas F., additional, Antoniou, Antonis C., additional, and Teo, Soo Hwang, additional

Published
2022
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15. Attitudes and training needs of oncologists and surgeons in mainstreaming breast cancer genetic counseling in a low‐to‐middle income Asian country

Author

Lee, Yong‐Quan, primary, Yoon, Sook‐Yee, additional, Hassan, Tiara, additional, Padmanabhan, Heamanthaa, additional, Yip, Cheng‐Har, additional, Keng, Wee‐Teik, additional, Thong, Meow‐Keong, additional, Ahmad Annuar, Muhammad Azrif, additional, Mohd Taib, Nur Aishah, additional, and Teo, Soo‐Hwang, additional

Published
2022
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16. Psychosocial outcome and health behaviour intent of breast cancer patients with BRCA1/2 and PALB2 pathogenic variants unselected by a priori risk

Author

Padmanabhan, Heamanthaa, primary, Hassan, Nur Tiara, additional, Wong, Siu-Wan, additional, Lee, Yong-Quan, additional, Lim, Joanna, additional, Hasan, Siti Norhidayu, additional, Yip, Cheng-Har, additional, Teo, Soo-Hwang, additional, Thong, Meow-Keong, additional, Mohd Taib, Nur Aishah, additional, and Yoon, Sook-Yee, additional

Published
2022
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18. Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort.

Author

Padmanabhan, Heamanthaa, Mariapun, Shivaani, Lee, Sheau‐Yee, Hassan, Nur Tiara, Lee, Daphne Shin‐Chi, Meiser, Bettina, Wong, Siu‐Wan, Lee, Yong‐Quan, Yip, Cheng‐Har, Teo, Soo‐Hwang, Thong, Meow‐Keong, Taib, Nur Aishah Mohd, and Yoon, Sook‐Yee

Abstract

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost‐effective cancer control even in low‐ and middle‐income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short‐ and long‐term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1‐month and 2‐year post‐disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2‐year post‐result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post‐result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture‐specific genetic counseling strategies. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore

Author

Ng, Pei Sze, primary, Boonen, Rick ACM, additional, Wijaya, Eldarina, additional, Chong, Chan Eng, additional, Sharma, Milan, additional, Knaup, Sabine, additional, Mariapun, Shivaani, additional, Ho, Weang Kee, additional, Lim, Joanna, additional, Yoon, Sook-Yee, additional, Mohd Taib, Nur Aishah, additional, See, Mee Hoong, additional, Li, Jingmei, additional, Lim, Swee Ho, additional, Tan, Ern Yu, additional, Tan, Benita Kiat-Tee, additional, Tan, Su-Ming, additional, Tan, Veronique Kiat-Mien, additional, van Dam, Rob Martinus, additional, Rahmat, Kartini, additional, Yip, Cheng Har, additional, Carvalho, Sara, additional, Luccarini, Craig, additional, Baynes, Caroline, additional, Dunning, Alison M, additional, Antoniou, Antonis, additional, van Attikum, Haico, additional, Easton, Douglas F, additional, Hartman, Mikael, additional, and Teo, Soo Hwang, additional

Published
2021
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23. Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Author

Silvestri, Valentina, Leslie, Goska, Barnes, Daniel R, CIMBA Group, Agnarsson, Bjarni A, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L, Barkardottir, Rosa B, Barroso, Alicia, Barrowdale, Daniel, Benitez, Javier, Bonanni, Bernardo, Borg, Ake, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Capalbo, Carlo, Campbell, Ian, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah V, Cortesi, Laura, Couch, Fergus J, De La Hoya, Miguel, Diez, Orland, Ding, Yuan Chun, Domchek, Susan, Easton, Douglas F, Ejlertsen, Bent, Engel, Christoph, Evans, D Gareth, Feliubadalò, Lidia, Foretova, Lenka, Fostira, Florentia, Géczi, Lajos, Gerdes, Anne-Marie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Hahnen, Eric, Hogervorst, Frans BL, Hopper, John L, Hulick, Peter J, Isaacs, Claudine, Izquierdo, Angel, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M, Joseph, Vijai, Konstantopoulou, Irene, Kurian, Allison W, Kwong, Ava, Landucci, Elisabetta, Lesueur, Fabienne, Loud, Jennifer T, Machackova, Eva, Mai, Phuong L, Majidzadeh-A, Keivan, Manoukian, Siranoush, Montagna, Marco, Moserle, Lidia, Mulligan, Anna Marie, Nathanson, Katherine L, Nevanlinna, Heli, Ngeow, Joanne, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Osorio, Ana, Papi, Laura, Park, Sue K, Pedersen, Inge Sokilde, Perez-Segura, Pedro, Petersen, Annabeth H, Pinto, Pedro, Porfirio, Berardino, Pujana, Miquel Angel, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U, Rosenzweig, Barak, Rossing, Maria, Santamariña, Marta, Schmutzler, Rita K, Senter, Leigha, Simard, Jacques, Singer, Christian F, Solano, Angela R, Southey, Melissa C, Steele, Linda, Steinsnyder, Zoe, Stoppa-Lyonnet, Dominique, Tan, Yen Yen, Teixeira, Manuel R, Teo, Soo H, Terry, Mary Beth, Thomassen, Mads, Toland, Amanda E, Torres-Esquius, Sara, Tung, Nadine, Van Asperen, Christi J, Vega, Ana, Viel, Alessandra, Vierstraete, Jeroen, Wappenschmidt, Barbara, Weitzel, Jeffrey N, Wieme, Greet, Yoon, Sook-Yee, Zorn, Kristin K, McGuffog, Lesley, Parsons, Michael T, Hamann, Ute, Greene, Mark H, Kirk, Judy A, Neuhausen, Susan L, Rebbeck, Timothy R, Tischkowitz, Marc, Chenevix-Trench, Georgia, Antoniou, Antonis C, Friedman, Eitan, Ottini, Laura, Leslie, Goska [0000-0001-5756-6222], Barnes, Daniel [0000-0002-3781-7570], Easton, Douglas [0000-0003-2444-3247], Tischkowitz, Marc [0000-0002-7880-0628], Antoniou, Antonis [0000-0001-9223-3116], and Apollo - University of Cambridge Repository

Subjects
Adult, Aged, 80 and over, BRCA2 Protein, Male, endocrine system diseases, Adolescent, BRCA1 Protein, Middle Aged, Young Adult, Phenotype, Neoplasms, Humans, skin and connective tissue diseases, Germ-Line Mutation, Aged, Retrospective Studies
Abstract

IMPORTANCE: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. OBJECTIVE: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. MAIN OUTCOMES AND MEASURES: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. RESULTS: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P < .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P < .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P < .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P < .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier. CONCLUSIONS AND RELEVANCE: Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.

Published
2020
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24. Characterization of the cancer spectrum in men with germline BRCA1 and BRCA2 pathogenic variants

Author

Silvestri, Valentina, Leslie, Goska, Barnes, Daniel R., Agnarsson, Bjarni A., Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Barkardottir, Rosa B., Barroso, Alicia, Barrowdale, Daniel, Benitez, Javier, Bonanni, Bernardo, Borg, Ake, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Capalbo, Carlo, Campbell, Ian, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah V., Cortesi, Laura, Couch, Fergus J., de la Hoya, Miguel, Diez, Orland, Ding, Yuan Chun, Domchek, Susan, Easton, Douglas F., Ejlertsen, Bent, Engel, Christoph, Evans, D. Gareth, Feliubadalò, Lidia, Foretova, Lenka, Fostira, Florentia, Géczi, Lajos, Gerdes, Anne-Marie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Hahnen, Eric, Hogervorst, Frans B. L., Hopper, John L., Hulick, Peter J., Isaacs, Claudine, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Joseph, Vijai, Konstantopoulou, Irene, Kurian, Allison W., Kwong, Ava, Landucci, Elisabetta, Lesueur, Fabienne, Loud, Jennifer T., Machackova, Eva, Mai, Phuong L., Majidzadeh-A, Keivan, Manoukian, Siranoush, Montagna, Marco, Moserle, Lidia, Mulligan, Anna Marie, Nathanson, Katherine L., Nevanlinna, Heli, Ngeow Yuen Ye, Joanne, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Osorio, Ana, Papi, Laura, Park, Sue K., Pedersen, Inge Sokilde, Perez-Segura, Pedro, Petersen, Annabeth H., Pinto, Pedro, Porfirio, Berardino, Pujana, Miquel Angel, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rosenzweig, Barak, Rossing, Maria, Santamariña, Marta, Schmutzler, Rita K., Senter, Leigha, Simard, Jacques, Singer, Christian F., Solano, Angela R., Southey, Melissa C., Steele, Linda, Steinsnyder, Zoe, Stoppa-Lyonnet, Dominique, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Thomassen, Mads, Toland, Amanda E., Torres-Esquius, Sara, Tung, Nadine, van Asperen, Christi J., Vega, Ana, Viel, Alessandra, Vierstraete, Jeroen, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Wieme, Greet, Yoon, Sook-Yee, Zorn, Kristin K., Mcguffog, Lesley, Parsons, Michael T., Hamann, Ute, Greene, Mark H., Kirk, Judy A., Neuhausen, Susan L., Rebbeck, Timothy R., Tischkowitz, Marc, Chenevix-Trench, Georgia, Antoniou, Antonis C., Friedman, Eitan, and Ottini, Laura

Subjects
male cancers, BRCA, cancer spectrum
Published
2020

25. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, Vivek L., Busch, Evan L., Friebel, Tara M., Cronin, Angel, Leslie, Goska, McGuffog, Lesley, Adlard, Julian, Agata, Simona, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Artioli, Grazia, Arver, Brita, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barnes, Daniel R., Barroso, Alicia, Barrowdale, Daniel, Belotti, Muriel, Benitez, Javier, Bertelsen, Brigitte, Blok, Marinus J., Bodrogi, Istvan, Bonadona, Valerie, Bonanni, Bernardo, Bondavalli, Davide, Boonen, Susanne E., Borde, Julika, Borg, Ake, Bradbury, Angela R., Brady, Angela, Brewer, Carole, Brunet, Joan, Buecher, Bruno, Buys, Saundra S., Cabezas-Camarero, Santiago, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Campbell, Ian G., Carnevali, Ileana, Carrasco, Estela, Chan, Tsun L., Chu, Annie T. W., Chung, Wendy K., Claes, Kathleen B. M., Cook, Jackie, Cortesi, Laura, Couch, Fergus J., Daly, Mary B., Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, Della Puppa, Lara, Dennis, Joe, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., 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, Feliubadalo, Lidia, Foretova, Lenka, Fostira, Florentia, Fountzilas, George, Frost, Debra, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Geczi, Lajos, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gutierrez-Barrera, Angelica M., Hahnen, Eric, Hamann, Ute, Hauke, Jan, Herold, Natalie, Hogervorst, Frans B. L., Honisch, Ellen, Hopper, John L., Hulick, Peter J., Izatt, Louise, Jager, Agnes, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, Jensen, Thomas Dyrso, Johannsson, Oskar Th, John, Esther M., Joseph, Vijai, Kang, Eunyoung, Kast, Karin, Kiiski, Johanna, I, Kim, Sung-Won, Kim, Zisun, Ko, Kwang-Pil, Konstantopoulou, Irene, Kramer, Gero, Krogh, Lotte, Kruse, Torben A., Kwong, Ava, Larsen, Mirjam, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Lee, Jihyoun, Lee, Jong Won, Lee, Min Hyuk, Lemke, Johannes, Lesueur, Fabienne, Liljegren, Annelie, Lindblom, Annika, Llovet, Patricia, Lopez-Fernandez, Adria, Lopez-Perolio, Irene, Lorca, Victor, Loud, Jennifer T., Ma, Edmond S. K., Mai, Phuong L., Manoukian, Siranoush, Mari, Veronique, Martin, Lynn, Matricardi, Laura, Mebirouk, Noura, Medici, Veronica, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Mensenkamp, Arjen R., Miller, Clare, Gomes, Denise Molina, Montagna, Marco, Mooij, Thea M., Moserle, Lidia, Mouret-Fourme, Emmanuelle, Mulligan, Anna Marie, Nathanson, Katherine L., Navratilova, Marie, Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C. Cilius, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, I, Ong, Kai-Ren, Osorio, Ana, Ott, Claus-Eric, Palli, Domenico, Park, Sue K., Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Peixoto, Ana, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth Hogh, Porteous, Mary E., Angel Pujana, Miguel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad U., Rhiem, Kerstin, Rizzolo, Piera, Robson, Mark E., Rookus, Matti A., Rossing, Caroline M., Ruddy, Kathryn J., Santos, Catarina, Saule, Claire, Scarpitta, Rosa, Schmutzler, Rita K., Schuster, Helene, Senter, Leigha, Seynaeve, Caroline M., Shah, Payal D., Sharma, Priyanka, Shin, Vivian Y., Silvestri, Valentina, Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Snape, Katie, Solano, Angela R., Soucy, Penny, Southey, Melissa C., Spurdle, Amanda B., Steele, Linda, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Stradella, Agostina, Sunde, Lone, Sutter, Christian, Tan, Yen Y., Teixeira, Manuel R., Teo, Soo Hwang, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tommasi, Stefania, Torres, Diana, Toss, Angela, Trainer, Alison H., Tung, Nadine, van Asperen, Christi J., van der Baan, Frederieke H., van der Kolk, Lizet E., van der Luijt, Rob B., van Hest, Liselotte P., Varesco, Liliana, Varon-Mateeva, Raymonda, Viel, Alessandra, Vierstrate, Jeroen, Villa, Roberta, von Wachenfeldt, Anna, Wagner, Philipp, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Wieme, Greet, Yadav, Siddhartha, Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zorn, Kristin K., D'Amico, Anthony, V, Freedman, Matthew L., Pomerantz, Mark M., Chenevix-Trench, Georgia, Antoniou, Antonis C., Neuhausen, Susan L., Ottini, Laura, Nielsen, Henriette Roed, Rebbeck, Timothy R., Patel, Vivek L., Busch, Evan L., Friebel, Tara M., Cronin, Angel, Leslie, Goska, McGuffog, Lesley, Adlard, Julian, Agata, Simona, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Artioli, Grazia, Arver, Brita, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barnes, Daniel R., Barroso, Alicia, Barrowdale, Daniel, Belotti, Muriel, Benitez, Javier, Bertelsen, Brigitte, Blok, Marinus J., Bodrogi, Istvan, Bonadona, Valerie, Bonanni, Bernardo, Bondavalli, Davide, Boonen, Susanne E., Borde, Julika, Borg, Ake, Bradbury, Angela R., Brady, Angela, Brewer, Carole, Brunet, Joan, Buecher, Bruno, Buys, Saundra S., Cabezas-Camarero, Santiago, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Campbell, Ian G., Carnevali, Ileana, Carrasco, Estela, Chan, Tsun L., Chu, Annie T. W., Chung, Wendy K., Claes, Kathleen B. M., Cook, Jackie, Cortesi, Laura, Couch, Fergus J., Daly, Mary B., Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, Della Puppa, Lara, Dennis, Joe, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., 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, Feliubadalo, Lidia, Foretova, Lenka, Fostira, Florentia, Fountzilas, George, Frost, Debra, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Geczi, Lajos, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gutierrez-Barrera, Angelica M., Hahnen, Eric, Hamann, Ute, Hauke, Jan, Herold, Natalie, Hogervorst, Frans B. L., Honisch, Ellen, Hopper, John L., Hulick, Peter J., Izatt, Louise, Jager, Agnes, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, Jensen, Thomas Dyrso, Johannsson, Oskar Th, John, Esther M., Joseph, Vijai, Kang, Eunyoung, Kast, Karin, Kiiski, Johanna, I, Kim, Sung-Won, Kim, Zisun, Ko, Kwang-Pil, Konstantopoulou, Irene, Kramer, Gero, Krogh, Lotte, Kruse, Torben A., Kwong, Ava, Larsen, Mirjam, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Lee, Jihyoun, Lee, Jong Won, Lee, Min Hyuk, Lemke, Johannes, Lesueur, Fabienne, Liljegren, Annelie, Lindblom, Annika, Llovet, Patricia, Lopez-Fernandez, Adria, Lopez-Perolio, Irene, Lorca, Victor, Loud, Jennifer T., Ma, Edmond S. K., Mai, Phuong L., Manoukian, Siranoush, Mari, Veronique, Martin, Lynn, Matricardi, Laura, Mebirouk, Noura, Medici, Veronica, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Mensenkamp, Arjen R., Miller, Clare, Gomes, Denise Molina, Montagna, Marco, Mooij, Thea M., Moserle, Lidia, Mouret-Fourme, Emmanuelle, Mulligan, Anna Marie, Nathanson, Katherine L., Navratilova, Marie, Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C. Cilius, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, I, Ong, Kai-Ren, Osorio, Ana, Ott, Claus-Eric, Palli, Domenico, Park, Sue K., Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Peixoto, Ana, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth Hogh, Porteous, Mary E., Angel Pujana, Miguel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad U., Rhiem, Kerstin, Rizzolo, Piera, Robson, Mark E., Rookus, Matti A., Rossing, Caroline M., Ruddy, Kathryn J., Santos, Catarina, Saule, Claire, Scarpitta, Rosa, Schmutzler, Rita K., Schuster, Helene, Senter, Leigha, Seynaeve, Caroline M., Shah, Payal D., Sharma, Priyanka, Shin, Vivian Y., Silvestri, Valentina, Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Snape, Katie, Solano, Angela R., Soucy, Penny, Southey, Melissa C., Spurdle, Amanda B., Steele, Linda, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Stradella, Agostina, Sunde, Lone, Sutter, Christian, Tan, Yen Y., Teixeira, Manuel R., Teo, Soo Hwang, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tommasi, Stefania, Torres, Diana, Toss, Angela, Trainer, Alison H., Tung, Nadine, van Asperen, Christi J., van der Baan, Frederieke H., van der Kolk, Lizet E., van der Luijt, Rob B., van Hest, Liselotte P., Varesco, Liliana, Varon-Mateeva, Raymonda, Viel, Alessandra, Vierstrate, Jeroen, Villa, Roberta, von Wachenfeldt, Anna, Wagner, Philipp, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Wieme, Greet, Yadav, Siddhartha, Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zorn, Kristin K., D'Amico, Anthony, V, Freedman, Matthew L., Pomerantz, Mark M., Chenevix-Trench, Georgia, Antoniou, Antonis C., Neuhausen, Susan L., Ottini, Laura, Nielsen, Henriette Roed, and Rebbeck, Timothy R.

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. Weevaluated whether PSVs inBRCA1/2 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 30 region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.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.

Published
2020

26. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families

Author

Yang, Xin, Leslie, Goska, Doroszuk, Alicja, Schneider, Sandra, Allen, Jamie, Decker, Brennan, Dunning, Alison M., Redman, James, Scarth, James, Plaskocinska, Inga, Luccarini, Craig, Shah, Mitul, Pooley, Karen, Dorling, Leila, Lee, Andrew, Adank, Muriel A., Adlard, Julian, Aittomaki, Kristiina, Andrulis, Irene L., Ang, Peter, Barwell, Julian, Bernstein, Jonine L., Bobolis, Kristie, Borg, Ake, Blomqvist, Carl, Claes, Kathleen B. M., Concannon, Patrick, Cuggia, Adeline, Culver, Julie O., Damiola, Francesca, de Pauw, Antoine, Diez, Orland, Dolinsky, Jill S., Domchek, Susan M., Engel, Christoph, Evans, D. Gareth, Fostira, Florentia, Garber, Judy, Golmard, Lisa, Goode, Ellen L., Gruber, Stephen B., Hahnen, Eric, Hake, Christopher, Heikkinen, Tuomas, Hurley, Judith E., Janavicius, Ramunas, Kleibl, Zdenek, Kleiblova, Petra, Konstantopoulou, Irene, Kvist, Anders, Laduca, Holly, Lee, Ann S. G., Lesueur, Fabienne, Maher, Eamonn R., Mannermaa, Arto, Manoukian, Siranoush, McFarland, Rachel, McKinnon, Wendy, Meindl, Alfons, Metcalfe, Kelly, Taib, Nur Aishah Mohd, Moilanen, Jukka, Nathanson, Katherine L., Neuhausen, Susan, Ng, Pei Sze, Nguyen-Dumont, Tu, Nielsen, Sarah M., Obermair, Florian, Offit, Kenneth, Olopade, Olufunmilayo, I, Ottini, Laura, Penkert, Judith, Pylkas, Katri, Radice, Paolo, Ramus, Susan J., Rudaitis, Vilius, Side, Lucy, Silva-Smith, Rachel, Silvestri, Valentina, Skytte, Anne-Bine, Slavin, Thomas, Soukupova, Jana, Tondini, Carlo, Trainer, Alison H., Unzeitig, Gary, Usha, Lydia, Hansen, Thomas van Overeem, Whitworth, James, Wood, Marie, Yip, Cheng Har, Yoon, Sook-Yee, Yussuf, Amal, Zogopoulos, George, Goldgar, David, Hopper, John L., Chenevix-Trench, Georgia, Pharoah, Paul, George, Sophia H. L., Balmana, Judith, Houdayer, Claude, James, Paul, El-Haffaf, Zaki, Ehrencrona, Hans, Janatova, Marketa, Peterlongo, Paolo, Nevanlinna, Heli, Schmutzler, Rita, Teo, Soo-Hwang, Robson, Mark, Pal, Tuya, Couch, Fergus, Weitzel, Jeffrey N., Elliott, Aaron, Southey, Melissa, Winqvist, Robert, Easton, Douglas F., Foulkes, William D., Antoniou, Antonis C., Tischkowitz, Marc, Yang, Xin, Leslie, Goska, Doroszuk, Alicja, Schneider, Sandra, Allen, Jamie, Decker, Brennan, Dunning, Alison M., Redman, James, Scarth, James, Plaskocinska, Inga, Luccarini, Craig, Shah, Mitul, Pooley, Karen, Dorling, Leila, Lee, Andrew, Adank, Muriel A., Adlard, Julian, Aittomaki, Kristiina, Andrulis, Irene L., Ang, Peter, Barwell, Julian, Bernstein, Jonine L., Bobolis, Kristie, Borg, Ake, Blomqvist, Carl, Claes, Kathleen B. M., Concannon, Patrick, Cuggia, Adeline, Culver, Julie O., Damiola, Francesca, de Pauw, Antoine, Diez, Orland, Dolinsky, Jill S., Domchek, Susan M., Engel, Christoph, Evans, D. Gareth, Fostira, Florentia, Garber, Judy, Golmard, Lisa, Goode, Ellen L., Gruber, Stephen B., Hahnen, Eric, Hake, Christopher, Heikkinen, Tuomas, Hurley, Judith E., Janavicius, Ramunas, Kleibl, Zdenek, Kleiblova, Petra, Konstantopoulou, Irene, Kvist, Anders, Laduca, Holly, Lee, Ann S. G., Lesueur, Fabienne, Maher, Eamonn R., Mannermaa, Arto, Manoukian, Siranoush, McFarland, Rachel, McKinnon, Wendy, Meindl, Alfons, Metcalfe, Kelly, Taib, Nur Aishah Mohd, Moilanen, Jukka, Nathanson, Katherine L., Neuhausen, Susan, Ng, Pei Sze, Nguyen-Dumont, Tu, Nielsen, Sarah M., Obermair, Florian, Offit, Kenneth, Olopade, Olufunmilayo, I, Ottini, Laura, Penkert, Judith, Pylkas, Katri, Radice, Paolo, Ramus, Susan J., Rudaitis, Vilius, Side, Lucy, Silva-Smith, Rachel, Silvestri, Valentina, Skytte, Anne-Bine, Slavin, Thomas, Soukupova, Jana, Tondini, Carlo, Trainer, Alison H., Unzeitig, Gary, Usha, Lydia, Hansen, Thomas van Overeem, Whitworth, James, Wood, Marie, Yip, Cheng Har, Yoon, Sook-Yee, Yussuf, Amal, Zogopoulos, George, Goldgar, David, Hopper, John L., Chenevix-Trench, Georgia, Pharoah, Paul, George, Sophia H. L., Balmana, Judith, Houdayer, Claude, James, Paul, El-Haffaf, Zaki, Ehrencrona, Hans, Janatova, Marketa, Peterlongo, Paolo, Nevanlinna, Heli, Schmutzler, Rita, Teo, Soo-Hwang, Robson, Mark, Pal, Tuya, Couch, Fergus, Weitzel, Jeffrey N., Elliott, Aaron, Southey, Melissa, Winqvist, Robert, Easton, Douglas F., Foulkes, William D., Antoniou, Antonis C., and Tischkowitz, Marc

Abstract

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 x 10(-76)), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 x 10(-3)), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 x 10(-3)), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 x 10(-2)). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 x 10(-3)). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical

Published
2020

27. Characterization of the Cancer Spectrum in Men with Germline BRCA1 and BRCA2 Pathogenic Variants:Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Author

Silvestri, Valentina, Leslie, Goska, Barnes, Daniel R., Agnarsson, Bjarni A., Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Barkardottir, Rosa B., Barroso, Alicia, Barrowdale, Daniel, Benitez, Javier, Bonanni, Bernardo, Borg, Ake, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Capalbo, Carlo, Campbell, Ian, Chung, Wendy K., Claes, Kathleen B.M., Colonna, Sarah V., Cortesi, Laura, Couch, Fergus J., De La Hoya, Miguel, Diez, Orland, Ding, Yuan Chun, Domchek, Susan, Easton, Douglas F., Ejlertsen, Bent, Engel, Christoph, Evans, D. Gareth, Feliubadalò, Lidia, Foretova, Lenka, Fostira, Florentia, Géczi, Lajos, Gerdes, Anne Marie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Hahnen, Eric, Hogervorst, Frans B.L., Hopper, John L., Hulick, Peter J., Isaacs, Claudine, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Joseph, Vijai, Konstantopoulou, Irene, Kurian, Allison W., Kwong, Ava, Landucci, Elisabetta, Lesueur, Fabienne, Loud, Jennifer T., Machackova, Eva, Mai, Phuong L., Majidzadeh-A, Keivan, Manoukian, Siranoush, Montagna, Marco, Moserle, Lidia, Mulligan, Anna Marie, Nathanson, Katherine L., Nevanlinna, Heli, Ngeow Yuen Ye, Joanne, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Osorio, Ana, Papi, Laura, Park, Sue K., Pedersen, Inge Sokilde, Perez-Segura, Pedro, Petersen, Annabeth H., Pinto, Pedro, Porfirio, Berardino, Pujana, Miquel Angel, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rosenzweig, Barak, Rossing, Maria, Santamariña, Marta, Schmutzler, Rita K., Senter, Leigha, Simard, Jacques, Singer, Christian F., Solano, Angela R., Southey, Melissa C., Steele, Linda, Steinsnyder, Zoe, Stoppa-Lyonnet, Dominique, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Thomassen, Mads, Toland, Amanda E., Torres-Esquius, Sara, Tung, Nadine, Van Asperen, Christi J., Vega, Ana, Viel, Alessandra, Vierstraete, Jeroen, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Wieme, Greet, Yoon, Sook Yee, Zorn, Kristin K., Mcguffog, Lesley, Parsons, Michael T., Hamann, Ute, Greene, Mark H., Kirk, Judy A., Neuhausen, Susan L., Rebbeck, Timothy R., Tischkowitz, Marc, Chenevix-Trench, Georgia, Antoniou, Antonis C., Friedman, Eitan, Ottini, Laura, Silvestri, Valentina, Leslie, Goska, Barnes, Daniel R., Agnarsson, Bjarni A., Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Barkardottir, Rosa B., Barroso, Alicia, Barrowdale, Daniel, Benitez, Javier, Bonanni, Bernardo, Borg, Ake, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Capalbo, Carlo, Campbell, Ian, Chung, Wendy K., Claes, Kathleen B.M., Colonna, Sarah V., Cortesi, Laura, Couch, Fergus J., De La Hoya, Miguel, Diez, Orland, Ding, Yuan Chun, Domchek, Susan, Easton, Douglas F., Ejlertsen, Bent, Engel, Christoph, Evans, D. Gareth, Feliubadalò, Lidia, Foretova, Lenka, Fostira, Florentia, Géczi, Lajos, Gerdes, Anne Marie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Hahnen, Eric, Hogervorst, Frans B.L., Hopper, John L., Hulick, Peter J., Isaacs, Claudine, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Joseph, Vijai, Konstantopoulou, Irene, Kurian, Allison W., Kwong, Ava, Landucci, Elisabetta, Lesueur, Fabienne, Loud, Jennifer T., Machackova, Eva, Mai, Phuong L., Majidzadeh-A, Keivan, Manoukian, Siranoush, Montagna, Marco, Moserle, Lidia, Mulligan, Anna Marie, Nathanson, Katherine L., Nevanlinna, Heli, Ngeow Yuen Ye, Joanne, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Osorio, Ana, Papi, Laura, Park, Sue K., Pedersen, Inge Sokilde, Perez-Segura, Pedro, Petersen, Annabeth H., Pinto, Pedro, Porfirio, Berardino, Pujana, Miquel Angel, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rosenzweig, Barak, Rossing, Maria, Santamariña, Marta, Schmutzler, Rita K., Senter, Leigha, Simard, Jacques, Singer, Christian F., Solano, Angela R., Southey, Melissa C., Steele, Linda, Steinsnyder, Zoe, Stoppa-Lyonnet, Dominique, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Thomassen, Mads, Toland, Amanda E., Torres-Esquius, Sara, Tung, Nadine, Van Asperen, Christi J., Vega, Ana, Viel, Alessandra, Vierstraete, Jeroen, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Wieme, Greet, Yoon, Sook Yee, Zorn, Kristin K., Mcguffog, Lesley, Parsons, Michael T., Hamann, Ute, Greene, Mark H., Kirk, Judy A., Neuhausen, Susan L., Rebbeck, Timothy R., Tischkowitz, Marc, Chenevix-Trench, Georgia, Antoniou, Antonis C., Friedman, Eitan, and Ottini, Laura

Abstract

Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. Design, Setting, and Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Results: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P <.001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P <.001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P <.001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P <.001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P =.008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P =.001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P =.003) of being a BRCA2 PV carrier. Conclusions and Relevance: Significant differences in the cancer sp

Published
2020

28. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, Vivek L, Busch, Evan L, Friebel, Tara M, Cronin, Angel, Leslie, Goska, McGuffog, Lesley, Adlard, Julian, Agata, Simona, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Artioli, Grazia, Arver, Brita, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barnes, Daniel R, Barroso, Alicia, Barrowdale, Daniel, Belotti, Muriel, Benitez, Javier, Bertelsen, Birgitte, Blok, Marinus J, Bodrogi, Istvan, Bonadona, Valérie, Bonanni, Bernardo, Bondavalli, Davide, Boonen, Susanne E, Borde, Julika, Borg, Ake, Bradbury, Angela R, Brady, Angela, Brewer, Carole, Brunet, Joan, Buecher, Bruno, Buys, Saundra S, Cabezas-Camarero, Santiago, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A, Calvello, Mariarosaria, Campbell, Ian G, Carnevali, Ileana, Carrasco, Estela, Chan, Tsun L, Chu, Annie T W, Chung, Wendy K, Claes, Kathleen B M, Collaborators, Gemo Study, Collaborators, Embrace, Cook, Jackie, Cortesi, Laura, Couch, Fergus J, Daly, Mary B, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, Puppa, Lara Della, Dennis, Joe, Díez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M, 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, Foretova, Lenka, Fostira, Florentia, Fountzilas, George, Frost, Debra, García-Barberán, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Géczi, Lajos, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gutierrez-Barrera, Angelica M, Hahnen, Eric, Hamann, Ute, Hauke, Jan, Herold, Natalie, Hogervorst, Frans B L, Honisch, Ellen, Hopper, John L, Hulick, Peter J, Investigators, KConFab, Investigators, Hebon, Izatt, Louise, Jager, Agnes, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, Jensen, Thomas Dyrso, Johannsson, Oskar Th, John, Esther M, Joseph, Vijai, Kang, Eunyoung, Kast, Karin, Kiiski, Johanna I, Kim, Sung-Won, Kim, Zisun, Ko, Kwang-Pil, Konstantopoulou, Irene, Kramer, Gero, Krogh, Lotte, Kruse, Torben A, Kwong, Ava, Larsen, Mirjam, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Lee, Jihyoun, Lee, Jong Won, Lee, Min Hyuk, Lemke, Johannes, Lesueur, Fabienne, Liljegren, Annelie, Lindblom, Annika, Llovet, Patricia, Lopez-Fernández, Adria, Lopez-Perolio, Irene, Lorca, Victor, Loud, Jennifer T, Ma, Edmond S K, Mai, Phuong L, Manoukian, Siranoush, Mari, Veronique, Martin, Lynn, Matricardi, Laura, Mebirouk, Noura, Medici, Veronica, Meijers-Heijboer, Hanne E J, Meindl, Alfons, Mensenkamp, Arjen R, Miller, Clare, Gomes, Denise Molina, Montagna, Marco, Mooij, Thea M, Moserle, Lidia, Mouret-Fourme, Emmanuelle, Mulligan, Anna Marie, Nathanson, Katherine L, Navratilova, Marie, Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C Cilius, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Ong, Kai-Ren, Osorio, Ana, Ott, Claus-Eric, Palli, Domenico, Park, Sue K, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Peixoto, Ana, Pérez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth Høgh, Porteous, Mary E, Pujana, Miguel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad U, Rhiem, Kerstin, Rizzolo, Piera, Robson, Mark E, Rookus, Matti A, Rossing, Caroline M, Ruddy, Kathryn J, Santos, Catarina, Saule, Claire, Scarpitta, Rosa, Schmutzler, Rita K, Schuster, Hélène, Senter, Leigha, Seynaeve, Caroline M, Shah, Payal D, Sharma, Priyanka, Shin, Vivian Y, Silvestri, Valentina, Simard, Jacques, Singer, Christian F, Skytte, Anne-Bine, Snape, Katie, Solano, Angela R, Soucy, Penny, Southey, Melissa C, Spurdle, Amanda B, Steele, Linda, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Stradella, Agostina, Sunde, Lone, Sutter, Christian, Tan, Yen Y, Teixeira, Manuel R, Teo, Soo Hwang, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E, Tommasi, Stefania, Torres, Diana, Toss, Angela, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J, van der Baan, Frederieke H, van der Kolk, Lizet E, van der Luijt, Rob B, van Hest, Liselotte P, Varesco, Liliana, Varon-Mateeva, Raymonda, Viel, Alessandra, Vierstraete, Jeroen, Villa, Roberta, von Wachenfeldt, Anna, Wagner, Philipp, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N, Wieme, Greet, Yadav, Siddhartha, Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zorn, Kristin K, D'Amico, Anthony V, Freedman, Matthew L, Pomerantz, Mark M, Chenevix-Trench, Georgia, Antoniou, Antonis C, Neuhausen, Susan L, Ottini, Laura, Nielsen, Henriette Roed, Rebbeck, Timothy R, Patel, Vivek L, Busch, Evan L, Friebel, Tara M, Cronin, Angel, Leslie, Goska, McGuffog, Lesley, Adlard, Julian, Agata, Simona, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Artioli, Grazia, Arver, Brita, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barnes, Daniel R, Barroso, Alicia, Barrowdale, Daniel, Belotti, Muriel, Benitez, Javier, Bertelsen, Birgitte, Blok, Marinus J, Bodrogi, Istvan, Bonadona, Valérie, Bonanni, Bernardo, Bondavalli, Davide, Boonen, Susanne E, Borde, Julika, Borg, Ake, Bradbury, Angela R, Brady, Angela, Brewer, Carole, Brunet, Joan, Buecher, Bruno, Buys, Saundra S, Cabezas-Camarero, Santiago, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A, Calvello, Mariarosaria, Campbell, Ian G, Carnevali, Ileana, Carrasco, Estela, Chan, Tsun L, Chu, Annie T W, Chung, Wendy K, Claes, Kathleen B M, Collaborators, Gemo Study, Collaborators, Embrace, Cook, Jackie, Cortesi, Laura, Couch, Fergus J, Daly, Mary B, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, Puppa, Lara Della, Dennis, Joe, Díez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M, 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, Foretova, Lenka, Fostira, Florentia, Fountzilas, George, Frost, Debra, García-Barberán, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Géczi, Lajos, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gutierrez-Barrera, Angelica M, Hahnen, Eric, Hamann, Ute, Hauke, Jan, Herold, Natalie, Hogervorst, Frans B L, Honisch, Ellen, Hopper, John L, Hulick, Peter J, Investigators, KConFab, Investigators, Hebon, Izatt, Louise, Jager, Agnes, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, Jensen, Thomas Dyrso, Johannsson, Oskar Th, John, Esther M, Joseph, Vijai, Kang, Eunyoung, Kast, Karin, Kiiski, Johanna I, Kim, Sung-Won, Kim, Zisun, Ko, Kwang-Pil, Konstantopoulou, Irene, Kramer, Gero, Krogh, Lotte, Kruse, Torben A, Kwong, Ava, Larsen, Mirjam, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Lee, Jihyoun, Lee, Jong Won, Lee, Min Hyuk, Lemke, Johannes, Lesueur, Fabienne, Liljegren, Annelie, Lindblom, Annika, Llovet, Patricia, Lopez-Fernández, Adria, Lopez-Perolio, Irene, Lorca, Victor, Loud, Jennifer T, Ma, Edmond S K, Mai, Phuong L, Manoukian, Siranoush, Mari, Veronique, Martin, Lynn, Matricardi, Laura, Mebirouk, Noura, Medici, Veronica, Meijers-Heijboer, Hanne E J, Meindl, Alfons, Mensenkamp, Arjen R, Miller, Clare, Gomes, Denise Molina, Montagna, Marco, Mooij, Thea M, Moserle, Lidia, Mouret-Fourme, Emmanuelle, Mulligan, Anna Marie, Nathanson, Katherine L, Navratilova, Marie, Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C Cilius, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Ong, Kai-Ren, Osorio, Ana, Ott, Claus-Eric, Palli, Domenico, Park, Sue K, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Peixoto, Ana, Pérez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth Høgh, Porteous, Mary E, Pujana, Miguel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad U, Rhiem, Kerstin, Rizzolo, Piera, Robson, Mark E, Rookus, Matti A, Rossing, Caroline M, Ruddy, Kathryn J, Santos, Catarina, Saule, Claire, Scarpitta, Rosa, Schmutzler, Rita K, Schuster, Hélène, Senter, Leigha, Seynaeve, Caroline M, Shah, Payal D, Sharma, Priyanka, Shin, Vivian Y, Silvestri, Valentina, Simard, Jacques, Singer, Christian F, Skytte, Anne-Bine, Snape, Katie, Solano, Angela R, Soucy, Penny, Southey, Melissa C, Spurdle, Amanda B, Steele, Linda, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Stradella, Agostina, Sunde, Lone, Sutter, Christian, Tan, Yen Y, Teixeira, Manuel R, Teo, Soo Hwang, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E, Tommasi, Stefania, Torres, Diana, Toss, Angela, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J, van der Baan, Frederieke H, van der Kolk, Lizet E, van der Luijt, Rob B, van Hest, Liselotte P, Varesco, Liliana, Varon-Mateeva, Raymonda, Viel, Alessandra, Vierstraete, Jeroen, Villa, Roberta, von Wachenfeldt, Anna, Wagner, Philipp, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N, Wieme, Greet, Yadav, Siddhartha, Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zorn, Kristin K, D'Amico, Anthony V, Freedman, Matthew L, Pomerantz, Mark M, Chenevix-Trench, Georgia, Antoniou, Antonis C, Neuhausen, Susan L, Ottini, Laura, Nielsen, Henriette Roed, and Rebbeck, Timothy R

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.

Published
2020

30. Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes

Author

Yoon, Sook-Yee, primary, Wong, Siu Wan, additional, Lim, Joanna, additional, Ahmad, Syuhada, additional, Mariapun, Shivaani, additional, Padmanabhan, Heamanthaa, additional, Hassan, Nur Tiara, additional, Lau, Shao Yan, additional, Ch'ng, Gaik-Siew, additional, Haniffa, Muzhirah, additional, Ong, Winnie P, additional, Rethanavelu, Kavitha, additional, Moey, Lip Hen, additional, Keng, Wee Teik, additional, Omar, Jamil, additional, Mohd Abas, Mohd Norazam, additional, Yong, Chee Meng, additional, Ramasamy, Vickneswaren, additional, Md Noor, Mohd Rushdan, additional, Aliyas, Ismail, additional, Lim, Michael C K, additional, Suberamaniam, Anuradha, additional, Mat Adenan, Noor Azmi, additional, Ahmad, Zatul Akmar, additional, Ho, Gwo Fuang, additional, Abdul Malik, Rozita, additional, Subramaniam, Suguna, additional, Khoo, Boom Ping, additional, Raja, Arivendran, additional, Chin, Yeung Sing, additional, Sim, Wee Wee, additional, Teh, Beng Hock, additional, Kho, Swee Kiong, additional, Ong, Eunice S E, additional, Voon, Pei Jye, additional, Ismail, Ghazali, additional, Lee, Chui Ling, additional, Abdullah, Badrul Zaman, additional, Loo, Kwong Sheng, additional, Lim, Chun Sen, additional, Lee, Saw Joo, additional, Lim, Keng Joo Lim, additional, Shafiee, Mohamad Nasir, additional, Ismail, Fuad, additional, Latiff, Zarina Abdul, additional, Ismail, Mohd Pazudin, additional, Mohamed Jamli, Mohamad Faiz, additional, Kumarasamy, Suresh, additional, Leong, Kin Wah, additional, Low, John, additional, Md Yusof, Mastura, additional, Ahmad Mustafa, Ahmad Muzamir, additional, Mat Ali, Nor Huda, additional, Makanjang, Mary, additional, Tayib, Shahila, additional, Cheah, Nellie, additional, Lim, Boon Kiong, additional, Fong, Chee Kin, additional, Foo, Yoke Ching, additional, Mellor Abdullah, Matin, additional, Tan, Teck Sin, additional, Chow, Doris S Y, additional, Ho, Kean Fatt, additional, Raman, Rakesh, additional, Radzi, Ahmad, additional, Deniel, Azura, additional, Teoh, Daren C Y, additional, Ang, Soo Fan, additional, Joseph, Joseph K, additional, Ng, Paul Hock Oon, additional, Tho, Lye-Mun, additional, Ahmad, Azura Rozila, additional, Muin, Ileena, additional, Bleiker, Eveline, additional, George, Angela, additional, Thong, Meow-Keong, additional, Woo, Yin Ling, additional, and Teo, Soo Hwang, additional

Published
2021
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32. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families

Author

Yang, Xin, primary, Leslie, Goska, additional, Doroszuk, Alicja, additional, Schneider, Sandra, additional, Allen, Jamie, additional, Decker, Brennan, additional, Dunning, Alison M., additional, Redman, James, additional, Scarth, James, additional, Plaskocinska, Inga, additional, Luccarini, Craig, additional, Shah, Mitul, additional, Pooley, Karen, additional, Dorling, Leila, additional, Lee, Andrew, additional, Adank, Muriel A., additional, Adlard, Julian, additional, Aittomäki, Kristiina, additional, Andrulis, Irene L., additional, Ang, Peter, additional, Barwell, Julian, additional, Bernstein, Jonine L., additional, Bobolis, Kristie, additional, Borg, Åke, additional, Blomqvist, Carl, additional, Claes, Kathleen B.M., additional, Concannon, Patrick, additional, Cuggia, Adeline, additional, Culver, Julie O., additional, Damiola, Francesca, additional, de Pauw, Antoine, additional, Diez, Orland, additional, Dolinsky, Jill S., additional, Domchek, Susan M., additional, Engel, Christoph, additional, Evans, D. Gareth, additional, Fostira, Florentia, additional, Garber, Judy, additional, Golmard, Lisa, additional, Goode, Ellen L., additional, Gruber, Stephen B., additional, Hahnen, Eric, additional, Hake, Christopher, additional, Heikkinen, Tuomas, additional, Hurley, Judith E., additional, Janavicius, Ramunas, additional, Kleibl, Zdenek, additional, Kleiblova, Petra, additional, Konstantopoulou, Irene, additional, Kvist, Anders, additional, Laduca, Holly, additional, Lee, Ann S.G., additional, Lesueur, Fabienne, additional, Maher, Eamonn R., additional, Mannermaa, Arto, additional, Manoukian, Siranoush, additional, McFarland, Rachel, additional, McKinnon, Wendy, additional, Meindl, Alfons, additional, Metcalfe, Kelly, additional, Mohd Taib, Nur Aishah, additional, Moilanen, Jukka, additional, Nathanson, Katherine L., additional, Neuhausen, Susan, additional, Ng, Pei Sze, additional, Nguyen-Dumont, Tu, additional, Nielsen, Sarah M., additional, Obermair, Florian, additional, Offit, Kenneth, additional, Olopade, Olufunmilayo I., additional, Ottini, Laura, additional, Penkert, Judith, additional, Pylkäs, Katri, additional, Radice, Paolo, additional, Ramus, Susan J., additional, Rudaitis, Vilius, additional, Side, Lucy, additional, Silva-Smith, Rachel, additional, Silvestri, Valentina, additional, Skytte, Anne-Bine, additional, Slavin, Thomas, additional, Soukupova, Jana, additional, Tondini, Carlo, additional, Trainer, Alison H., additional, Unzeitig, Gary, additional, Usha, Lydia, additional, van Overeem Hansen, Thomas, additional, Whitworth, James, additional, Wood, Marie, additional, Yip, Cheng Har, additional, Yoon, Sook-Yee, additional, Yussuf, Amal, additional, Zogopoulos, George, additional, Goldgar, David, additional, Hopper, John L., additional, Chenevix-Trench, Georgia, additional, Pharoah, Paul, additional, George, Sophia H.L., additional, Balmaña, Judith, additional, Houdayer, Claude, additional, James, Paul, additional, El-Haffaf, Zaki, additional, Ehrencrona, Hans, additional, Janatova, Marketa, additional, Peterlongo, Paolo, additional, Nevanlinna, Heli, additional, Schmutzler, Rita, additional, Teo, Soo-Hwang, additional, Robson, Mark, additional, Pal, Tuya, additional, Couch, Fergus, additional, Weitzel, Jeffrey N., additional, Elliott, Aaron, additional, Southey, Melissa, additional, Winqvist, Robert, additional, Easton, Douglas F., additional, Foulkes, William D., additional, Antoniou, Antonis C., additional, and Tischkowitz, Marc, additional

Published
2020
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33. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, Vivek L., primary, Busch, Evan L., additional, Friebel, Tara M., additional, Cronin, Angel, additional, Leslie, Goska, additional, McGuffog, Lesley, additional, Adlard, Julian, additional, Agata, Simona, additional, Agnarsson, Bjarni A., additional, Ahmed, Munaza, additional, Aittomäki, Kristiina, additional, Alducci, Elisa, additional, Andrulis, Irene L., additional, Arason, Adalgeir, additional, Arnold, Norbert, additional, Artioli, Grazia, additional, Arver, Brita, additional, Auber, Bernd, additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barkardottir, Rosa B., additional, Barnes, Daniel R., additional, Barroso, Alicia, additional, Barrowdale, Daniel, additional, Belotti, Muriel, additional, Benitez, Javier, additional, Bertelsen, Birgitte, additional, Blok, Marinus J., additional, Bodrogi, Istvan, additional, Bonadona, Valérie, additional, Bonanni, Bernardo, additional, Bondavalli, Davide, additional, Boonen, Susanne E., additional, Borde, Julika, additional, Borg, Ake, additional, Bradbury, Angela R., additional, Brady, Angela, additional, Brewer, Carole, additional, Brunet, Joan, additional, Buecher, Bruno, additional, Buys, Saundra S., additional, Cabezas-Camarero, Santiago, additional, Caldés, Trinidad, additional, Caliebe, Almuth, additional, Caligo, Maria A., additional, Calvello, Mariarosaria, additional, Campbell, Ian G., additional, Carnevali, Ileana, additional, Carrasco, Estela, additional, Chan, Tsun L., additional, Chu, Annie T.W., additional, Chung, Wendy K., additional, Claes, Kathleen B.M., additional, Collaborators, GEMO Study, additional, Collaborators, EMBRACE, additional, Cook, Jackie, additional, Cortesi, Laura, additional, Couch, Fergus J., additional, Daly, Mary B., additional, Damante, Giuseppe, additional, Darder, Esther, additional, Davidson, Rosemarie, additional, de la Hoya, Miguel, additional, Puppa, Lara Della, additional, Dennis, Joe, additional, Díez, Orland, additional, Ding, Yuan Chun, additional, Ditsch, Nina, additional, Domchek, Susan M., additional, Donaldson, Alan, additional, Dworniczak, Bernd, additional, Easton, Douglas F., additional, Eccles, Diana M., additional, Eeles, Rosalind A., additional, Ehrencrona, Hans, additional, Ejlertsen, Bent, additional, Engel, Christoph, additional, Evans, D. Gareth, additional, Faivre, Laurence, additional, Faust, Ulrike, additional, Feliubadaló, Lídia, additional, Foretova, Lenka, additional, Fostira, Florentia, additional, Fountzilas, George, additional, Frost, Debra, additional, García-Barberán, Vanesa, additional, Garre, Pilar, additional, Gauthier-Villars, Marion, additional, Géczi, Lajos, additional, Gehrig, Andrea, additional, Gerdes, Anne-Marie, additional, Gesta, Paul, additional, Giannini, Giuseppe, additional, Glendon, Gord, additional, Godwin, Andrew K., additional, Goldgar, David E., additional, Greene, Mark H., additional, Gutierrez-Barrera, Angelica M., additional, Hahnen, Eric, additional, Hamann, Ute, additional, Hauke, Jan, additional, Herold, Natalie, additional, Hogervorst, Frans B.L., additional, Honisch, Ellen, additional, Hopper, John L., additional, Hulick, Peter J., additional, Investigators, KConFab, additional, Investigators, HEBON, additional, Izatt, Louise, additional, Jager, Agnes, additional, James, Paul, additional, Janavicius, Ramunas, additional, Jensen, Uffe Birk, additional, Jensen, Thomas Dyrso, additional, Johannsson, Oskar Th., additional, John, Esther M., additional, Joseph, Vijai, additional, Kang, Eunyoung, additional, Kast, Karin, additional, Kiiski, Johanna I., additional, Kim, Sung-Won, additional, Kim, Zisun, additional, Ko, Kwang-Pil, additional, Konstantopoulou, Irene, additional, Kramer, Gero, additional, Krogh, Lotte, additional, Kruse, Torben A., additional, Kwong, Ava, additional, Larsen, Mirjam, additional, Lasset, Christine, additional, Lautrup, Charlotte, additional, Lazaro, Conxi, additional, Lee, Jihyoun, additional, Lee, Jong Won, additional, Lee, Min Hyuk, additional, Lemke, Johannes, additional, Lesueur, Fabienne, additional, Liljegren, Annelie, additional, Lindblom, Annika, additional, Llovet, Patricia, additional, Lopez-Fernández, Adria, additional, Lopez-Perolio, Irene, additional, Lorca, Victor, additional, Loud, Jennifer T., additional, Ma, Edmond S.K., additional, Mai, Phuong L., additional, Manoukian, Siranoush, additional, Mari, Veronique, additional, Martin, Lynn, additional, Matricardi, Laura, additional, Mebirouk, Noura, additional, Medici, Veronica, additional, Meijers-Heijboer, Hanne E.J., additional, Meindl, Alfons, additional, Mensenkamp, Arjen R., additional, Miller, Clare, additional, Gomes, Denise Molina, additional, Montagna, Marco, additional, Mooij, Thea M., additional, Moserle, Lidia, additional, Mouret-Fourme, Emmanuelle, additional, Mulligan, Anna Marie, additional, Nathanson, Katherine L., additional, Navratilova, Marie, additional, Nevanlinna, Heli, additional, Niederacher, Dieter, additional, Nielsen, Finn C. Cilius, additional, Nikitina-Zake, Liene, additional, Offit, Kenneth, additional, Olah, Edith, additional, Olopade, Olufunmilayo I., additional, Ong, Kai-Ren, additional, Osorio, Ana, additional, Ott, Claus-Eric, additional, Palli, Domenico, additional, Park, Sue K., additional, Parsons, Michael T., additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Peixoto, Ana, additional, Pérez-Segura, Pedro, additional, Peterlongo, Paolo, additional, Petersen, Annabeth Høgh, additional, Porteous, Mary E., additional, Pujana, Miguel Angel, additional, Radice, Paolo, additional, Ramser, Juliane, additional, Rantala, Johanna, additional, Rashid, Muhammad U., additional, Rhiem, Kerstin, additional, Rizzolo, Piera, additional, Robson, Mark E., additional, Rookus, Matti A., additional, Rossing, Caroline M., additional, Ruddy, Kathryn J., additional, Santos, Catarina, additional, Saule, Claire, additional, Scarpitta, Rosa, additional, Schmutzler, Rita K., additional, Schuster, Hélène, additional, Senter, Leigha, additional, Seynaeve, Caroline M., additional, Shah, Payal D., additional, Sharma, Priyanka, additional, Shin, Vivian Y., additional, Silvestri, Valentina, additional, Simard, Jacques, additional, Singer, Christian F., additional, Skytte, Anne-Bine, additional, Snape, Katie, additional, Solano, Angela R., additional, Soucy, Penny, additional, Southey, Melissa C., additional, Spurdle, Amanda B., additional, Steele, Linda, additional, Steinemann, Doris, additional, Stoppa-Lyonnet, Dominique, additional, Stradella, Agostina, additional, Sunde, Lone, additional, Sutter, Christian, additional, Tan, Yen Y., additional, Teixeira, Manuel R., additional, Teo, Soo Hwang, additional, Thomassen, Mads, additional, Tibiletti, Maria Grazia, additional, Tischkowitz, Marc, additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Tommasi, Stefania, additional, Torres, Diana, additional, Toss, Angela, additional, Trainer, Alison H., additional, Tung, Nadine, additional, van Asperen, Christi J., additional, van der Baan, Frederieke H., additional, van der Kolk, Lizet E., additional, van der Luijt, Rob B., additional, van Hest, Liselotte P., additional, Varesco, Liliana, additional, Varon-Mateeva, Raymonda, additional, Viel, Alessandra, additional, Vierstraete, Jeroen, additional, Villa, Roberta, additional, von Wachenfeldt, Anna, additional, Wagner, Philipp, additional, Wang-Gohrke, Shan, additional, Wappenschmidt, Barbara, additional, Weitzel, Jeffrey N., additional, Wieme, Greet, additional, Yadav, Siddhartha, additional, Yannoukakos, Drakoulis, additional, Yoon, Sook-Yee, additional, Zanzottera, Cristina, additional, Zorn, Kristin K., additional, D'Amico, Anthony V., additional, Freedman, Matthew L., additional, Pomerantz, Mark M., additional, Chenevix-Trench, Georgia, additional, Antoniou, Antonis C., additional, Neuhausen, Susan L., additional, Ottini, Laura, additional, Nielsen, Henriette Roed, additional, and Rebbeck, Timothy R., additional

Published
2020
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35. Decision-making for Risk-reducing Salpingo-oophorectomy (RRSO) in Southeast Asian BRCA Mutation Carriers With Breast Cancer: A Qualitative Study.

Author

Sa'at, Hamizah, Lee, Yew-Kong, Yoon, Sook-Yee, Wong, Siu Wan, Woo, Yin Ling, Barlow-Stewart, Kristine, and Mohd Taib, Nur Aishah

Subjects
BREAST tumor risk factors, WELL-being, GENETIC mutation, OVARIAN tumors, BRCA genes, RESEARCH methodology, ATTITUDE (Psychology), HUMAN sexuality, INTERVIEWING, COGNITION, RISK assessment, QUALITATIVE research, MOTHERHOOD, RISK perception, HYSTERO-oophorectomy, DESCRIPTIVE statistics, DECISION making in clinical medicine, ANXIETY, DATA analysis software, BREAST tumors
Abstract

Background: The uptake of risk-reducing salpingo-oophorectomy (RRSO) in Asian countries is variable despite being the most effective option for ovarian cancer risk reduction in BRCA mutation carriers. Exploration of factors which may impact the RRSO decision-making of BRCA mutation carriers from Malaysia, a developing country in Southeast Asia, was undertaken. Methods: In-depth interviews with 28 Malaysian BRCA mutation carriers with a history of breast cancer were conducted in addition to observing their RRSO decision-making consultations in the clinic. Results: The decision-making considerations among the carriers were centered around the overarching theme of "Negotiating cancer risk and womanhood priorities," with the following themes: (1) risk perception, (2) self-preservation, (3) motherhood obligation, and (4) the preciousness of marriage. Cognitive knowledge of BRCA risk was often conceptualized based on personal and family history of cancer, personal beliefs, and faith. Many women reported fears that RRSO would affect them physically and emotionally, worrying about the post-surgical impact on their motherhood responsibilities. Nevertheless, some reported feeling obliged to choose RRSO for the sake of their children. For some, their husband's support and approval were critical, with emotional well-being and sexuality reportedly perceived as important to sustaining married life. Despite reporting hesitancy toward RRSO, women's decisions about choosing this option evolved as their priorities changed at different stages of life. Conclusions: Recognizing during clinic encounters with Malaysian women that RRSO decision-making involves negotiating the likelihood of developing cancer with the societal priorities of being a woman, mother, and wife may serve to support their decision-making. [ABSTRACT FROM AUTHOR]

Published
2022
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36. The needs of Southeast Asian BRCA mutation carriers considering risk-reducing salpingo-oophorectomy: a qualitative study.

Author

Sa'at, Hamizah, Lee, Yew-Kong, Yoon, Sook-Yee, Wong, Siu Wan, Woo, Yin Ling, Barlow-Stewart, Kristine, and Mohd Taib, Nur Aishah

Subjects
BRCA genes, SALPINGO-oophorectomy, GENETIC mutation, OVARIAN cancer, QUALITATIVE research, RELIGIOUS adherents, SPOUSES
Abstract

The decision to have risk-reducing salpingo-oophorectomy (RRSO) by BRCA mutation carriers to reduce the risk of ovarian cancer is difficult. The choice involves trade-offs in terms of its risks and benefits. To date, understanding the decision-making needs of RRSO among Southeast Asian BRCA mutation carriers is limited. This study aimed to explore the decision-making needs of Malaysian BRCA mutation carriers as an exemplar for the Southeast Asian community. In-depth interviews and clinic observations were conducted with 31 BRCA mutation carriers and analysed thematically. The core theme identified was 'Coping with complex information and alleviating uncertainties' with the following subthemes: (1) the need for an adjustment period, (2) information support, (3) social support and, (4) religious support. We found that women required time to accept their BRCA mutation status before they were ready to make a risk-reducing choice; that understanding complex genetic information and multiple risk management options can be an overwhelming experience; and obtaining further information and a second opinion were challenging. Many described the need for experiential information from other peer-carriers who had undergone RRSO. Support from their spouse and family members was thought to be essential for them to feel reassured with their decision. Many relied on religion to positively cope with cancer risk and cancer worry; Muslim BRCA carriers sought religious guidance through prayers and Islamic fatwas to feel more certain about their RRSO decision. These findings underscore the importance of the provision of resources and support that includes input from peers, husband, family members and religion to underpin the decision-making needs of Malaysian BRCA mutation carriers considering RRSO. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia

Author

Wen, Wei Xiong, Allen, Jamie, Lai, Kah Nyin, Mariapun, Shivaani, Hasan, Siti Norhidayu, Ng, Pei Sze, Lee, Daphne Shin-Chi, Lee, Sheau Yee, Yoon, Sook-Yee, Lim, Joanna, Lau, Shao Yan, Decker, Brennan, Pooley, Karen, Dorling, Leila, Luccarini, Craig, Baynes, Caroline, Conroy, Don M, Harrington, Patricia, Simard, Jacques, Yip, Cheng Har, Mohd Taib, Nur Aishah, Ho, Weang Kee, Antoniou, Antonis C, Dunning, Alison M, Easton, Douglas F, Teo, Soo Hwang, Teo, Soo Hwang [0000-0002-0444-590X], and Apollo - University of Cambridge Repository

Subjects
Adult, BRCA2 Protein, asian, BRCA1 Protein, Malaysia, Breast Neoplasms, Middle Aged, brca1, breast cancer, brca2, Case-Control Studies, Mutation, Practice Guidelines as Topic, Cancer Genetics, national comprehensive cancer network, Humans, Female, skin and connective tissue diseases, Germ-Line Mutation
Abstract

BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls. METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing. RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing. CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.

Published
2019

38. Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations

Author

Bancroft, Elizabeth K, Saya, Sibel, Page, Elizabeth C, Myhill, Kathryn, Thomas, Sarah, Pope, Jennifer, Chamberlain, Anthony, Hart, Rachel, Glover, Wayne, Cook, Jackie, Rosario, Derek J, Helfand, Brian T, Selkirk, Christina Hutten, Davidson, Rosemarie, Longmuir, Mark, Eccles, Diana M, Gadea, Neus, Brewer, Carole, Barwell, Julian, Salinas, Monica, Greenhalgh, Lynn, Tischkowitz, Marc, Henderson, Alex, Evans, David Gareth, Buys, Saundra S, Eeles, Rosalind A, Aaronson, Neil K, Eeles, Rosalind, Bancroft, Elizabeth, Page, Elizabeth, Kote-Jarai, Zsofia, Ardern-Jones, Audrey, Bangma, Chris, Castro, Elena, Dearnaley, David, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C, Johannsson, Oskar Thor, Khoo, Vincent, Eccles, Diana, Lilja, Hans, Evans, Gareth, Eyfjord, Jorunn, Lubinski, Jan, Maehle, Lovise, Mikropoulos, Christos, Millner, Alan, Mitra, Anita, Offman, Judith, Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Dias, Alex, Taylor, Natalie, D'Mello, Lucia, Pope, Jenny, James, Paul, Mitchell, Gillian, Shanley, Sue, Richardson, Kate, McKinley, Joanne, Petelin, Lara, Murphy, Morgan, Mascarenhas, Lyon, Murphy, Declan, Lam, Jimmy, Taylor, Louise, Miller, Cathy, Stapleton, Alan, Chong, Michael, Suthers, Graeme, Poplawski, Nicola, Tucker, Katherine, Andrews, Lesley, Duffy, Jessica, Millard, Richard, Ward, Robyn, Williams, Rachel, Stricker, Phillip, Kirk, Judy, Bowman, Michelle, Patel, Manish, Harris, Marion, O'Connell, Shona, Hunt, Clare, Smyth, Courtney, Frydenberg, Mark, Lindeman, Geoffrey, Shackleton, Kylie, Morton, Catherine, Susman, Rachel, McGaughran, Julie, Boon, Melanie, Pachter, Nicholas, Townshend, Sharron, Schofield, Lyn, Nicholls, Cassandra, Spigelman, Allan, Gleeson, Margaret, Amor, David, Burke, Jo, Patterson, Briony, Swindle, Peter, Scott, Rodney, Foulkes, William, Boshari, Talia, Aprikian, Armen, Jensen, Thomas, Bojeson, Anders, Osther, Palle, Skytte, Anne-Bine, Cruger, Dorthe, Tondering, Majbritt Kure, Gerdes, Anne-Marie, Schmutzler, Rita, Rhiem, Kerstin, Wihler, Petra, Kast, K, Griebsch, C, Johannsson, Oskar, Stefansdottir, Vigdis, Murthy, Vedang, Sarin, Rajiv, Awatagiri, Kasturi, Ghonge, Sujata, Kowtal, Pradnya, Mulgund, Gouri, Gallagher, David, Bambury, Richard, Farrell, Michael, Gallagher, Fergal, Kiernan, Ingrid, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Basevitch, Alon, Leibovici, Dan, Melzer, Ehud, Ben-Yehoshua, Sagi Josefsberg, Nicolai, Nicola, Radice, Paolo, Valdagni, Riccardo, Magnani, Tiziana, Gay, Simona, Teo, Soo Hwang, Tan, Hui Meng, Yoon, Sook-Yee, Thong, Meow Keong, Vasen, Hans, Ringleberg, Janneke, van Asperen, Christi, Kiemeney, Bart, van Zelst-Stams, Wendy, Ausems, Margreet GEM, van der Luijt, Rob B, van Os, Theo, Ruijs, Marielle WG, Adank, Muriel A, Oldenburg, Rogier A, Helderman-van den Enden, A Paula TJM, Caanen, BAH, Oosterwijk, Jan C, Moller, Pal, Brennhovd, Bjorn, Medvik, Heidi, Hanslien, Eldbjorg, Grindedal, Eli Marie, Cybulski, Cezary, Wokolorczyk, Dominika, Teixeira, Manuel, Maia, Sofia, Peixoto, Ana, Henrique, Rui, Oliveira, Jorge, Goncalves, Nuno, Araujo, Luis, Seixas, Manuela, Souto, Joao Paulo, Nogueira, Pedro, Copakova, Lucia, Zgajnar, Janez, Krajc, Mateja, Vrecar, Alenka, Capella, Gabriel, Ramon y Cajal, Teresa, Fisas, David, Mora, Josefina, Esquena, Salvador, Balmana, Judith, Morote, Juan, Liljegren, Annelie, Hjalm-Eriksson, Marie, Ekdahl, Karl-Johan, Carlsson, Stefan, George, Angela, Kemp, Zoe, Wiggins, Jennifer, Moss, Cathryn, Van As, Nicholas, Thompson, Alan, Ogden, Chris, Woodhouse, Christopher, Kumar, Pardeep, Evans, D Gareth, Bulman, Barbara, Rothwell, Jeanette, Tricker, Karen, Wise, Gillian, Mercer, Catherine, McBride, Donna, Costello, Philandra, Pearce, Allison, Torokwa, Audrey, Paterson, Joan, Clowes, Virginia, Taylor, Amy, Newcombe, Barbara, Walker, Lisa, Halliday, Dorothy, Stayner, Barbara, Fleming-Brown, D, Snape, Katie, Hanson, Helen, Hodgson, Shirley, Brice, Glen, Homfray, Tessa, Hammond, Carrie, Kohut, Kelly, Anjum, Uruj, Dearing, Audrey, Mencias, Mark, Potter, Alison, Renton, Caroline, Searle, Anne, Hill, Kathryn, Goodman, Selina, Garcia, Lynda, Devlin, Gemma, Everest, Sarah, Nadolski, Maria, Douglas, Fiona, Jobson, Irene, Paez, Edgar, Donaldson, Alan, Tomkins, Sue, Langman, Caroline, Jacobs, Chris, Pichert, Gabriella, Shaw, Adam, Kulkarni, Anju, Tripathi, Vishakha, Rose, Sarah, Compton, Cecilia, Watson, Michelle, Reinholtz, Cherylin, Brady, Angela, Dorkins, Huw, Melville, Athalie, Kosicka-Slawinska, Monika, Cummings, Carole, Kiesel, Vicki, Bartlett, Marion, Randhawa, Kashmir, Ellery, Natalie, Side, Lucy, Male, Alison, Simon, Kate, Rees, Katie, Tidey, Lizzie, Gurasashvili, Jana, Nevitt, Louise, Ingram, Stuart, Howell, Alice, Rosario, Derek, Catto, James, Howson, Joanne, Ong, Kai-Ren, Chapman, Cyril, Cole, Trevor, Heaton, Tricia, Hoffman, Jonathan, Burgess, Lucy, Huber, Camilla, Islam, Farah, Watt, Cathy, Duncan, Alexis, Kockelbergh, Roger, Mzazi, Shumikazi, Dineen, Amy, Sattar, Ayisha, Kaemba, Beckie, Sidat, Zahirah, Patel, Nafisa, Siguake, Kas, Birt, Angela, Poultney, Una, Umez-Eronini, Nkem, Mom, Jaswant, Sutton, Vivienne, Cornford, Philip, Bermingham, Nicola, Yesildag, Pembe, Treherne, Katy, Griffiths, Julie, Cogley, Lyn, Gott, Hannah, Rubinstein, Wendy S, Hulick, Peter, McGuire, Michael, Shevrin, Daniel, Kaul, Karen, Weissman, Scott, Newlin, Anna, Vogel, Kristen, Weiss, Shelly, Hook, Nicole, Buys, Saundra, Goldgar, David, Conner, Tom, Venne, Vickie, Stephenson, Robert, Dechet, Christopher, Domchek, Susan, Powers, Jacquelyn, Rustgi, Neil, Strom, Sara, Arun, Banu, Davis, John W, Yamamura, Yuko, Obeid, Elias, Giri, Veda, Gross, Laura, Bealin, Lisa, Cooney, Kathy, Stoffel, Elena, Okoth, Linda, Comm, IMPACT Study Steering, Collaborators, IMPACT, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), General Practice, Urology, and Clinical Genetics

Subjects
psychosocial, Male, Health Knowledge, Attitudes, Practice, Urological Oncology, Genes, BRCA2, Genes, BRCA1, #pcsm, RISK PERCEPTION, Anxiety, Hospital Anxiety and Depression Scale, FAMILY-HISTORY, PSA, 0302 clinical medicine, Quality of life, QUALITY-OF-LIFE, Risk Factors, Surveys and Questionnaires, Medicine, 030212 general & internal medicine, Longitudinal Studies, Depressió psíquica, Early Detection of Cancer, POPULATION, Prostatic Neoplasms/diagnosis, education.field_of_study, Prostate cancer, Depression, Anxiety/etiology, Urology & Nephrology, Middle Aged, Distress, Prostate cancer screening, Mental depression, #ProstateCancer, Estudi de casos, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, HEALTH, medicine.symptom, Psychosocial, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Urology, Depression/etiology, Population, HOSPITAL ANXIETY, Early Detection of Cancer/psychology, OVARIAN-CANCER, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, BRCA1/2, Internal medicine, Humans, education, Psychiatric Status Rating Scales, Càncer de pròstata, business.industry, Prostatic Neoplasms, BRCA1, BRCA2, quality of life, Case-Control Studies, Mutation, Perception, Case studies, business, PSYCHOLOGICAL IMPACT
Abstract

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICIPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS:A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening.

Published
2019

39. Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations

Author

Bancroft, Elizabeth K., Saya, Sibel, Page, Elizabeth C., Myhill, Kathryn, Thomas, Sarah, Pope, Jennifer, Chamberlain, Anthony, Hart, Rachel, Glover, Wayne, Cook, Jackie, Rosario, Derek J., Helfand, Brian T., Selkirk, Christina Hutten, Davidson, Rosemarie, Longmuir, Mark, Eccles, Diana M., Gadea, Neus, Brewer, Carole, Barwell, Julian, Salinas, Monica, Greenhalgh, Lynn, Tischkowitz, Marc, Henderson, Alex, Evans, David Gareth, Buys, Saundra S., Eeles, Rosalind A., Aaronson, Neil K., Eeles, Rosalind, Bancroft, Elizabeth, Page, Elizabeth, Kote-Jarai, Zsofia, Ardern-Jones, Audrey, Bangma, Chris, Castro, Elena, Dearnaley, David, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Johannsson, Oskar Thor, Khoo, Vincent, Eccles, Diana, Lilja, Hans, Evans, Gareth, Eyfjord, Jorunn, Lubinski, Jan, Maehle, Lovise, Mikropoulos, Christos, Millner, Alan, Mitra, Anita, Offman, Judith, Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Dias, Alex, Taylor, Natalie, D'Mello, Lucia, Pope, Jenny, James, Paul, Mitchell, Gillian, Shanley, Sue, Richardson, Kate, McKinley, Joanne, Petelin, Lara, Murphy, Morgan, Mascarenhas, Lyon, Murphy, Declan, Lam, Jimmy, Taylor, Louise, Miller, Cathy, Stapleton, Alan, Chong, Michael, Suthers, Graeme, Poplawski, Nicola, Tucker, Katherine, Andrews, Lesley, Duffy, Jessica, Millard, Richard, Ward, Robyn, Williams, Rachel, Stricker, Phillip, Kirk, Judy, Bowman, Michelle, Patel, Manish, Harris, Marion, O'Connell, Shona, Hunt, Clare, Smyth, Courtney, Frydenberg, Mark, Lindeman, Geoffrey, Shackleton, Kylie, Morton, Catherine, Susman, Rachel, McGaughran, Julie, Boon, Melanie, Pachter, Nicholas, Townshend, Sharron, Schofield, Lyn, Nicholls, Cassandra, Spigelman, Allan, Gleeson, Margaret, Amor, David, Burke, Jo, Patterson, Briony, Swindle, Peter, Scott, Rodney, Foulkes, William, Boshari, Talia, Aprikian, Armen, Jensen, Thomas, Bojeson, Anders, Osther, Palle, Skytte, Anne-Bine, Cruger, Dorthe, Tondering, Majbritt Kure, Gerdes, Anne-Marie, Schmutzler, Rita, Rhiem, Kerstin, Wihler, Petra, Kast, K., Griebsch, C., Johannsson, Oskar, Stefansdottir, Vigdis, Murthy, Vedang, Sarin, Rajiv, Awatagiri, Kasturi, Ghonge, Sujata, Kowtal, Pradnya, Mulgund, Gouri, Gallagher, David, Bambury, Richard, Farrell, Michael, Gallagher, Fergal, Kiernan, Ingrid, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Basevitch, Alon, Leibovici, Dan, Melzer, Ehud, Ben-Yehoshua, Sagi Josefsberg, Nicolai, Nicola, Radice, Paolo, Valdagni, Riccardo, Magnani, Tiziana, Gay, Simona, Teo, Soo Hwang, Tan, Hui Meng, Yoon, Sook-Yee, Thong, Meow Keong, Vasen, Hans, Ringleberg, Janneke, van Asperen, Christi, Kiemeney, Bart, van Zelst-Stams, Wendy, Ausems, Margreet G. E. M., van der Luijt, Rob B., van Os, Theo, Ruijs, Marielle W. G., Adank, Muriel A., Oldenburg, Rogier A., Helderman-van den Enden, A. Paula T. J. M., Caanen, B. A. H., Oosterwijk, Jan C., Moller, Pal, Brennhovd, Bjorn, Medvik, Heidi, Hanslien, Eldbjorg, Grindedal, Eli Marie, Cybulski, Cezary, Wokolorczyk, Dominika, Teixeira, Manuel, Maia, Sofia, Peixoto, Ana, Henrique, Rui, Oliveira, Jorge, Goncalves, Nuno, Araujo, Luis, Seixas, Manuela, Souto, Joao Paulo, Nogueira, Pedro, Copakova, Lucia, Zgajnar, Janez, Krajc, Mateja, Vrecar, Alenka, Capella, Gabriel, Ramon y Cajal, Teresa, Fisas, David, Mora, Josefina, Esquena, Salvador, Balmana, Judith, Morote, Juan, Liljegren, Annelie, Hjalm-Eriksson, Marie, Ekdahl, Karl-Johan, Carlsson, Stefan, George, Angela, Kemp, Zoe, Wiggins, Jennifer, Moss, Cathryn, Van As, Nicholas, Thompson, Alan, Ogden, Chris, Woodhouse, Christopher, Kumar, Pardeep, Evans, D. Gareth, Bulman, Barbara, Rothwell, Jeanette, Tricker, Karen, Wise, Gillian, Mercer, Catherine, McBride, Donna, Costello, Philandra, Pearce, Allison, Torokwa, Audrey, Paterson, Joan, Clowes, Virginia, Taylor, Amy, Newcombe, Barbara, Walker, Lisa, Halliday, Dorothy, Stayner, Barbara, Fleming-Brown, D., Snape, Katie, Hanson, Helen, Hodgson, Shirley, Brice, Glen, Homfray, Tessa, Hammond, Carrie, Kohut, Kelly, Anjum, Uruj, Dearing, Audrey, Mencias, Mark, Potter, Alison, Renton, Caroline, Searle, Anne, Hill, Kathryn, Goodman, Selina, Garcia, Lynda, Devlin, Gemma, Everest, Sarah, Nadolski, Maria, Douglas, Fiona, Jobson, Irene, Paez, Edgar, Donaldson, Alan, Tomkins, Sue, Langman, Caroline, Jacobs, Chris, Pichert, Gabriella, Shaw, Adam, Kulkarni, Anju, Tripathi, Vishakha, Rose, Sarah, Compton, Cecilia, Watson, Michelle, Reinholtz, Cherylin, Brady, Angela, Dorkins, Huw, Melville, Athalie, Kosicka-Slawinska, Monika, Cummings, Carole, Kiesel, Vicki, Bartlett, Marion, Randhawa, Kashmir, Ellery, Natalie, Side, Lucy, Male, Alison, Simon, Kate, Rees, Katie, Tidey, Lizzie, Gurasashvili, Jana, Nevitt, Louise, Ingram, Stuart, Howell, Alice, Rosario, Derek, Catto, James, Howson, Joanne, Ong, Kai-Ren, Chapman, Cyril, Cole, Trevor, Heaton, Tricia, Hoffman, Jonathan, Burgess, Lucy, Huber, Camilla, Islam, Farah, Watt, Cathy, Duncan, Alexis, Kockelbergh, Roger, Mzazi, Shumikazi, Dineen, Amy, Sattar, Ayisha, Kaemba, Beckie, Sidat, Zahirah, Patel, Nafisa, Siguake, Kas, Birt, Angela, Poultney, Una, Umez-Eronini, Nkem, Mom, Jaswant, Sutton, Vivienne, Cornford, Philip, Bermingham, Nicola, Yesildag, Pembe, Treherne, Katy, Griffiths, Julie, Cogley, Lyn, Gott, Hannah, Rubinstein, Wendy S., Hulick, Peter, McGuire, Michael, Shevrin, Daniel, Kaul, Karen, Weissman, Scott, Newlin, Anna, Vogel, Kristen, Weiss, Shelly, Hook, Nicole, Buys, Saundra, Goldgar, David, Conner, Tom, Venne, Vickie, Stephenson, Robert, Dechet, Christopher, Domchek, Susan, Powers, Jacquelyn, Rustgi, Neil, Strom, Sara, Arun, Banu, Davis, John W., Yamamura, Yuko, Obeid, Elias, Giri, Veda, Gross, Laura, Bealin, Lisa, Cooney, Kathy, Stoffel, Elena, Okoth, Linda, Bancroft, Elizabeth K., Saya, Sibel, Page, Elizabeth C., Myhill, Kathryn, Thomas, Sarah, Pope, Jennifer, Chamberlain, Anthony, Hart, Rachel, Glover, Wayne, Cook, Jackie, Rosario, Derek J., Helfand, Brian T., Selkirk, Christina Hutten, Davidson, Rosemarie, Longmuir, Mark, Eccles, Diana M., Gadea, Neus, Brewer, Carole, Barwell, Julian, Salinas, Monica, Greenhalgh, Lynn, Tischkowitz, Marc, Henderson, Alex, Evans, David Gareth, Buys, Saundra S., Eeles, Rosalind A., Aaronson, Neil K., Eeles, Rosalind, Bancroft, Elizabeth, Page, Elizabeth, Kote-Jarai, Zsofia, Ardern-Jones, Audrey, Bangma, Chris, Castro, Elena, Dearnaley, David, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Johannsson, Oskar Thor, Khoo, Vincent, Eccles, Diana, Lilja, Hans, Evans, Gareth, Eyfjord, Jorunn, Lubinski, Jan, Maehle, Lovise, Mikropoulos, Christos, Millner, Alan, Mitra, Anita, Offman, Judith, Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Dias, Alex, Taylor, Natalie, D'Mello, Lucia, Pope, Jenny, James, Paul, Mitchell, Gillian, Shanley, Sue, Richardson, Kate, McKinley, Joanne, Petelin, Lara, Murphy, Morgan, Mascarenhas, Lyon, Murphy, Declan, Lam, Jimmy, Taylor, Louise, Miller, Cathy, Stapleton, Alan, Chong, Michael, Suthers, Graeme, Poplawski, Nicola, Tucker, Katherine, Andrews, Lesley, Duffy, Jessica, Millard, Richard, Ward, Robyn, Williams, Rachel, Stricker, Phillip, Kirk, Judy, Bowman, Michelle, Patel, Manish, Harris, Marion, O'Connell, Shona, Hunt, Clare, Smyth, Courtney, Frydenberg, Mark, Lindeman, Geoffrey, Shackleton, Kylie, Morton, Catherine, Susman, Rachel, McGaughran, Julie, Boon, Melanie, Pachter, Nicholas, Townshend, Sharron, Schofield, Lyn, Nicholls, Cassandra, Spigelman, Allan, Gleeson, Margaret, Amor, David, Burke, Jo, Patterson, Briony, Swindle, Peter, Scott, Rodney, Foulkes, William, Boshari, Talia, Aprikian, Armen, Jensen, Thomas, Bojeson, Anders, Osther, Palle, Skytte, Anne-Bine, Cruger, Dorthe, Tondering, Majbritt Kure, Gerdes, Anne-Marie, Schmutzler, Rita, Rhiem, Kerstin, Wihler, Petra, Kast, K., Griebsch, C., Johannsson, Oskar, Stefansdottir, Vigdis, Murthy, Vedang, Sarin, Rajiv, Awatagiri, Kasturi, Ghonge, Sujata, Kowtal, Pradnya, Mulgund, Gouri, Gallagher, David, Bambury, Richard, Farrell, Michael, Gallagher, Fergal, Kiernan, Ingrid, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Basevitch, Alon, Leibovici, Dan, Melzer, Ehud, Ben-Yehoshua, Sagi Josefsberg, Nicolai, Nicola, Radice, Paolo, Valdagni, Riccardo, Magnani, Tiziana, Gay, Simona, Teo, Soo Hwang, Tan, Hui Meng, Yoon, Sook-Yee, Thong, Meow Keong, Vasen, Hans, Ringleberg, Janneke, van Asperen, Christi, Kiemeney, Bart, van Zelst-Stams, Wendy, Ausems, Margreet G. E. M., van der Luijt, Rob B., van Os, Theo, Ruijs, Marielle W. G., Adank, Muriel A., Oldenburg, Rogier A., Helderman-van den Enden, A. Paula T. J. M., Caanen, B. A. H., Oosterwijk, Jan C., Moller, Pal, Brennhovd, Bjorn, Medvik, Heidi, Hanslien, Eldbjorg, Grindedal, Eli Marie, Cybulski, Cezary, Wokolorczyk, Dominika, Teixeira, Manuel, Maia, Sofia, Peixoto, Ana, Henrique, Rui, Oliveira, Jorge, Goncalves, Nuno, Araujo, Luis, Seixas, Manuela, Souto, Joao Paulo, Nogueira, Pedro, Copakova, Lucia, Zgajnar, Janez, Krajc, Mateja, Vrecar, Alenka, Capella, Gabriel, Ramon y Cajal, Teresa, Fisas, David, Mora, Josefina, Esquena, Salvador, Balmana, Judith, Morote, Juan, Liljegren, Annelie, Hjalm-Eriksson, Marie, Ekdahl, Karl-Johan, Carlsson, Stefan, George, Angela, Kemp, Zoe, Wiggins, Jennifer, Moss, Cathryn, Van As, Nicholas, Thompson, Alan, Ogden, Chris, Woodhouse, Christopher, Kumar, Pardeep, Evans, D. Gareth, Bulman, Barbara, Rothwell, Jeanette, Tricker, Karen, Wise, Gillian, Mercer, Catherine, McBride, Donna, Costello, Philandra, Pearce, Allison, Torokwa, Audrey, Paterson, Joan, Clowes, Virginia, Taylor, Amy, Newcombe, Barbara, Walker, Lisa, Halliday, Dorothy, Stayner, Barbara, Fleming-Brown, D., Snape, Katie, Hanson, Helen, Hodgson, Shirley, Brice, Glen, Homfray, Tessa, Hammond, Carrie, Kohut, Kelly, Anjum, Uruj, Dearing, Audrey, Mencias, Mark, Potter, Alison, Renton, Caroline, Searle, Anne, Hill, Kathryn, Goodman, Selina, Garcia, Lynda, Devlin, Gemma, Everest, Sarah, Nadolski, Maria, Douglas, Fiona, Jobson, Irene, Paez, Edgar, Donaldson, Alan, Tomkins, Sue, Langman, Caroline, Jacobs, Chris, Pichert, Gabriella, Shaw, Adam, Kulkarni, Anju, Tripathi, Vishakha, Rose, Sarah, Compton, Cecilia, Watson, Michelle, Reinholtz, Cherylin, Brady, Angela, Dorkins, Huw, Melville, Athalie, Kosicka-Slawinska, Monika, Cummings, Carole, Kiesel, Vicki, Bartlett, Marion, Randhawa, Kashmir, Ellery, Natalie, Side, Lucy, Male, Alison, Simon, Kate, Rees, Katie, Tidey, Lizzie, Gurasashvili, Jana, Nevitt, Louise, Ingram, Stuart, Howell, Alice, Rosario, Derek, Catto, James, Howson, Joanne, Ong, Kai-Ren, Chapman, Cyril, Cole, Trevor, Heaton, Tricia, Hoffman, Jonathan, Burgess, Lucy, Huber, Camilla, Islam, Farah, Watt, Cathy, Duncan, Alexis, Kockelbergh, Roger, Mzazi, Shumikazi, Dineen, Amy, Sattar, Ayisha, Kaemba, Beckie, Sidat, Zahirah, Patel, Nafisa, Siguake, Kas, Birt, Angela, Poultney, Una, Umez-Eronini, Nkem, Mom, Jaswant, Sutton, Vivienne, Cornford, Philip, Bermingham, Nicola, Yesildag, Pembe, Treherne, Katy, Griffiths, Julie, Cogley, Lyn, Gott, Hannah, Rubinstein, Wendy S., Hulick, Peter, McGuire, Michael, Shevrin, Daniel, Kaul, Karen, Weissman, Scott, Newlin, Anna, Vogel, Kristen, Weiss, Shelly, Hook, Nicole, Buys, Saundra, Goldgar, David, Conner, Tom, Venne, Vickie, Stephenson, Robert, Dechet, Christopher, Domchek, Susan, Powers, Jacquelyn, Rustgi, Neil, Strom, Sara, Arun, Banu, Davis, John W., Yamamura, Yuko, Obeid, Elias, Giri, Veda, Gross, Laura, Bealin, Lisa, Cooney, Kathy, Stoffel, Elena, and Okoth, Linda

Abstract

Objectives To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. Particpants and Methods Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. Results A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. Conclusion This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to me

Published
2019

40. Communication about positive BRCA1 and BRCA2 genetic test results and uptake of testing in relatives in a diverse Asian setting.

Author

Lee, Daphne S.‐C., Meiser, Bettina, Mariapun, Shivaani, Hassan, Tiara, Yip, Cheng‐Har, Mohd Taib, Nur A., Teo, Soo‐Hwang, Thong, Meow‐Keong, and Yoon, Sook‐Yee

Abstract

The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty‐seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi‐structured interview guide. Fifty‐six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first‐ and second‐degree relatives were informed by the proband about the testing result and that 11.5% of eligible first‐ and second‐degree relatives had genetic testing. First‐degree relatives were more likely to have been informed and tested compared to second‐degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second‐degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Characterisation of protein-truncating and missense variants in PALB2in 15 768 women from Malaysia and Singapore

Author

Ng, Pei Sze, Boonen, Rick ACM, Wijaya, Eldarina, Chong, Chan Eng, Sharma, Milan, Knaup, Sabine, Mariapun, Shivaani, Ho, Weang Kee, Lim, Joanna, Yoon, Sook-Yee, Mohd Taib, Nur Aishah, See, Mee Hoong, Li, Jingmei, Lim, Swee Ho, Tan, Ern Yu, Tan, Benita Kiat-Tee, Tan, Su-Ming, Tan, Veronique Kiat-Mien, van Dam, Rob Martinus, Rahmat, Kartini, Yip, Cheng Har, Carvalho, Sara, Luccarini, Craig, Baynes, Caroline, Dunning, Alison M, Antoniou, Antonis, van Attikum, Haico, Easton, Douglas F, Hartman, Mikael, and Teo, Soo Hwang

Abstract

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Published
2022
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42. Oncologist-led BRCAcounselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes

Author

Yoon, Sook-Yee, Wong, Siu Wan, Lim, Joanna, Ahmad, Syuhada, Mariapun, Shivaani, Padmanabhan, Heamanthaa, Hassan, Nur Tiara, Lau, Shao Yan, Ch'ng, Gaik-Siew, Haniffa, Muzhirah, Ong, Winnie P, Rethanavelu, Kavitha, Moey, Lip Hen, Keng, Wee Teik, Omar, Jamil, Mohd Abas, Mohd Norazam, Yong, Chee Meng, Ramasamy, Vickneswaren, Md Noor, Mohd Rushdan, Aliyas, Ismail, Lim, Michael C K, Suberamaniam, Anuradha, Mat Adenan, Noor Azmi, Ahmad, Zatul Akmar, Ho, Gwo Fuang, Abdul Malik, Rozita, Subramaniam, Suguna, Khoo, Boom Ping, Raja, Arivendran, Chin, Yeung Sing, Sim, Wee Wee, Teh, Beng Hock, Kho, Swee Kiong, Ong, Eunice S E, Voon, Pei Jye, Ismail, Ghazali, Lee, Chui Ling, Abdullah, Badrul Zaman, Loo, Kwong Sheng, Lim, Chun Sen, Lee, Saw Joo, Lim, Keng Joo Lim, Shafiee, Mohamad Nasir, Ismail, Fuad, Latiff, Zarina Abdul, Ismail, Mohd Pazudin, Mohamed Jamli, Mohamad Faiz, Kumarasamy, Suresh, Leong, Kin Wah, Low, John, Md Yusof, Mastura, Ahmad Mustafa, Ahmad Muzamir, Mat Ali, Nor Huda, Makanjang, Mary, Tayib, Shahila, Cheah, Nellie, Lim, Boon Kiong, Fong, Chee Kin, Foo, Yoke Ching, Mellor Abdullah, Matin, Tan, Teck Sin, Chow, Doris S Y, Ho, Kean Fatt, Raman, Rakesh, Radzi, Ahmad, Deniel, Azura, Teoh, Daren C Y, Ang, Soo Fan, Joseph, Joseph K, Ng, Paul Hock Oon, Tho, Lye-Mun, Ahmad, Azura Rozila, Muin, Ileena, Bleiker, Eveline, George, Angela, Thong, Meow-Keong, Woo, Yin Ling, and Teo, Soo Hwang

Abstract

BackgroundIdentifying patients with BRCAmutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming.MethodsThe Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer.ResultsOncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1or BRCA2,and there was no difference between psychosocial measures for carriers in both arms.ConclusionThe MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

Published
2022
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43. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author

Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Weitzel, Jeffrey N., Chan, T. L., Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inez, Park, Sue Kyung, Torres, Diana, van Rensburg, Elizabeth J., McGuffog, Lesley, Parsons, Michael T., Leslie, Goska, Aalfs, Cora M., Abugattas, Julio, Adlard, Julian, Agata, Simona, Aittomaki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmana, Judith, Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valerie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Collee, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, SusanM., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadalo, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Galvao, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Gutierrez-Barrera, Angelica, Hahnen, Eric, Hauke, Jan, Henderson, Alex, Hentschel, Julia, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lazaro, Conxi, Lee, Annette, Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Manoukian, Siranoush, Mari, Veronique, Martinez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Ofverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teule, Alex, Thomas, Abigail, Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H., Tung, Nadine, van Asperen, Christi J., van der Hout, Annemieke H., van der Kolk, Lizet E., van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Antoniou, Antonis C., Nathanson, Katherine L., Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Weitzel, Jeffrey N., Chan, T. L., Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inez, Park, Sue Kyung, Torres, Diana, van Rensburg, Elizabeth J., McGuffog, Lesley, Parsons, Michael T., Leslie, Goska, Aalfs, Cora M., Abugattas, Julio, Adlard, Julian, Agata, Simona, Aittomaki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmana, Judith, Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valerie, Bonanni, Bernardo, Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Chung, Wendy K., Claes, Kathleen B. M., Collee, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, SusanM., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadalo, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Galvao, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Greene, Mark H., Gronwald, Jacek, Gutierrez-Barrera, Angelica, Hahnen, Eric, Hauke, Jan, Henderson, Alex, Hentschel, Julia, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lazaro, Conxi, Lee, Annette, Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Manoukian, Siranoush, Mari, Veronique, Martinez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Ofverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teule, Alex, Thomas, Abigail, Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H., Tung, Nadine, van Asperen, Christi J., van der Hout, Annemieke H., van der Kolk, Lizet E., van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Antoniou, Antonis C., and Nathanson, Katherine L.

Abstract

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

Published
2018

44. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author

Fundações de Amparo à Pesquisa (Brasil), Research Foundation - Flanders, University of Helsinki, Sigrid Juselius Foundation, Dutch Cancer Society, Netherlands Organization for Scientific Research, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Ministero della Salute, Istituto Oncologico Veneto, University of Tasmania, Australian Cancer Research Foundation, Ministry of Health and Welfare (South Korea), Charles University (Czech Republic), National Research Foundation Singapore, Russian Foundation for Basic Research, Istituto Toscano Tumori, Israel Cancer Association USA, Swedish Cancer Society, Foundation for Women's Cancer, University of Pittsburgh, Cancer Australia, American Cancer Society, The Ohio State University, National Institutes of Health (US), Cancer Research UK, European Commission, Canadian Institutes of Health Research, Department of Trade and Industry (UK), Susan G. Komen Foundation, Breast Cancer Research Foundation, Genome Canada, National Cancer Institute (US), Research Council of Lithuania, Cancer Association of South Africa, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Sanidad y Política Social (España), Associazione Italiana per la Ricerca sul Cancro, Fondazione Italiana per la Ricerca sul Cancro, Ministero dell'Istruzione, dell'Università e della Ricerca, Institut Pasteur, Fondazione Cenci Bolognetti, Greek Government, Pontificia Universidad Javeriana, Royal Marsden NHS Foundation Trust, Kansas State University, Fundación Mutua Madrileña, Ligue Nationale contre le Cancer (France), Georgetown University, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwamg, Thomassen, Mads, Mebirouk, Noura, Meijers-Heijboer, Hanne, Meindl, Alfons, Mensenkamp, Arjen R., Kruse, Torben A., Benitez, Javier, Mickys, Ugnius, Greene, Mark H., Miller, Austin, thomas, Abigail, Cook, Jackie, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Berger, Andreas, Nguyen, Huu Phuc, Palmero, Edenir Inêz, Davidson, Rosemarie, Bonadona, Valérie, Schmutzler, Rita Katharina, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Berger, Raanan, Hoya, Miguel de la, Osorio, Ana, Konstantopoulou, Irene, Papi, Laura, Papp, Janos, Senter, Leigha, Kyung Park, Sue, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Leeneer, Kim de, Peterlongo, Paolo, Blanco, Amie M., Thull, Darcy L., Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Shah, Payal D., Pujol, Pascal, Torres, Diana, Pauw, Antoine de, Radice, Paolo, Sharma, Priyanka, Side, Lucy E., Tischkowitz, Marc, Blazer, Kathleen R., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Rashid, Muhammad Usman, Gronwald, Jacek, McGuffog, Lesley, Sobol, Hagay, Southey, Melissa, Tognazzo, Silvia, Steele, Linda, Blok, Marinus J., Steinemann, Doris, Toland, Amanda Ewart, Topka, Sabine, Delnatte, Capucine, Trainer, Alison H., Tung, Nadine, Hahnen, Eric, Asperen, Christi J. van, Hout, Annemieke H. van der, Korach, Jacob, Hogervorst, Frans B. L., Leslie, Goska, Kolk, Lizet E. van der, Luijt, Rob B. van der, Weitzel, Jeffrey N., Heetvelde, Mattias van, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, Hauke, Jan, Laitman, Yael, Wachenfeldt, Anna von, Ramus, Susan J., Walker, Lisa, Díez, Orland, Wang-Gohrke, Shan, Aalfs, Cora M., Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Lasa, Adrian, Zidan, Jamal, HEBON, Lee, Min Hyuk, Bonanni, Bernardo, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Abugattas, Julio, Spurdle, Amanda B., Antoniou, Antonis C., Lasset, Christine, Nathanson, Katherine L., Sukiennicki, Grzegorz, Adlard, Julian, Agata, Simona, Bradbury, Angela R., Henderson, Alex, Aittomäki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Couch, Fergus J., Ding, Yuan Chun, Arun, Branu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Brewer, Carole, Balmaña, Judith, Hentschel, Julia, Barile, Monica, Buecher, Bruno, Buys, Saundra S., Ditsch, Nina, Lázaro, Conxi, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Rantala, Johanna, Honisch, Ellen, Chiquette, Jocelyne, Chung, Wendy K., Domchek, Susan M., Claes, Kathleen B., Lee, Annette T., Collée, J. Margriet, Evans, D. Gareth, Dorfling, Cecilia M., Velázquez Pérez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Rhiem, Kerstin, Easton, Douglas F., Eeles, Ros, Sutter, Christian, Schmidt, Ane Y., Imyanitov, Evgeny N., Ehrencrona, Hans, Ejlertsen, Bent, EMBRACE, Engel, Christoph, Engert, Stefanie, Faivre, Laurence, Feliubadaló, Lidia, Robson, Mark, szabo, Csilla I., Tan, Yen Y., Fert Ferrer, Sandra, Barkardottir, Rosa B., Foretova, Lenka, Fowler, Jeffrey, Isaacs, Claudine, Frost, Debra, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Teixeira, Manuel R., Gehrig, Andrea, Rodriguez, Gustavo C., Lester, Jenny, GEMO Study Collaborators, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Izat, Louise, Giraud, Sophie, Glendon, Gord, Terry, Mary Beth, Godwin, Andrew K., Izquierdo, Angel, Jakubowska, Anna, Lesueur, Fabienne, Rogers, Mark T., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Gutierrez-Barrera, Angelica, Chan, T. L., Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Liljegren, Annelie, KConFab Investigators, Rudaitis, Vilius, Kim, Sung-Won, Lindor, Noralane M., Longy, Michel, Teulé, Alex, Loud, Jennifer T., Lu, Karen H., Goldgar, David E., Lubinski, Jan, Machackova, Eva, Barrowdale, Daniel, Rensburg, Elizabeth J. van, Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzaz, Cristina, Parsons, Michael T., Matrai, Zoltan, Fundações de Amparo à Pesquisa (Brasil), Research Foundation - Flanders, University of Helsinki, Sigrid Juselius Foundation, Dutch Cancer Society, Netherlands Organization for Scientific Research, Asociación Española Contra el Cáncer, Generalitat de Catalunya, Ministero della Salute, Istituto Oncologico Veneto, University of Tasmania, Australian Cancer Research Foundation, Ministry of Health and Welfare (South Korea), Charles University (Czech Republic), National Research Foundation Singapore, Russian Foundation for Basic Research, Istituto Toscano Tumori, Israel Cancer Association USA, Swedish Cancer Society, Foundation for Women's Cancer, University of Pittsburgh, Cancer Australia, American Cancer Society, The Ohio State University, National Institutes of Health (US), Cancer Research UK, European Commission, Canadian Institutes of Health Research, Department of Trade and Industry (UK), Susan G. Komen Foundation, Breast Cancer Research Foundation, Genome Canada, National Cancer Institute (US), Research Council of Lithuania, Cancer Association of South Africa, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Sanidad y Política Social (España), Associazione Italiana per la Ricerca sul Cancro, Fondazione Italiana per la Ricerca sul Cancro, Ministero dell'Istruzione, dell'Università e della Ricerca, Institut Pasteur, Fondazione Cenci Bolognetti, Greek Government, Pontificia Universidad Javeriana, Royal Marsden NHS Foundation Trust, Kansas State University, Fundación Mutua Madrileña, Ligue Nationale contre le Cancer (France), Georgetown University, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwamg, Thomassen, Mads, Mebirouk, Noura, Meijers-Heijboer, Hanne, Meindl, Alfons, Mensenkamp, Arjen R., Kruse, Torben A., Benitez, Javier, Mickys, Ugnius, Greene, Mark H., Miller, Austin, thomas, Abigail, Cook, Jackie, Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Berger, Andreas, Nguyen, Huu Phuc, Palmero, Edenir Inêz, Davidson, Rosemarie, Bonadona, Valérie, Schmutzler, Rita Katharina, Niederacher, Dieter, Nielsen, Henriette Roed, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Berger, Raanan, Hoya, Miguel de la, Osorio, Ana, Konstantopoulou, Irene, Papi, Laura, Papp, Janos, Senter, Leigha, Kyung Park, Sue, Pasini, Barbara, Pedersen, Inge Sokilde, Peixoto, Ana, Peruga, Nina, Leeneer, Kim de, Peterlongo, Paolo, Blanco, Amie M., Thull, Darcy L., Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Shah, Payal D., Pujol, Pascal, Torres, Diana, Pauw, Antoine de, Radice, Paolo, Sharma, Priyanka, Side, Lucy E., Tischkowitz, Marc, Blazer, Kathleen R., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Rashid, Muhammad Usman, Gronwald, Jacek, McGuffog, Lesley, Sobol, Hagay, Southey, Melissa, Tognazzo, Silvia, Steele, Linda, Blok, Marinus J., Steinemann, Doris, Toland, Amanda Ewart, Topka, Sabine, Delnatte, Capucine, Trainer, Alison H., Tung, Nadine, Hahnen, Eric, Asperen, Christi J. van, Hout, Annemieke H. van der, Korach, Jacob, Hogervorst, Frans B. L., Leslie, Goska, Kolk, Lizet E. van der, Luijt, Rob B. van der, Weitzel, Jeffrey N., Heetvelde, Mattias van, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, Hauke, Jan, Laitman, Yael, Wachenfeldt, Anna von, Ramus, Susan J., Walker, Lisa, Díez, Orland, Wang-Gohrke, Shan, Aalfs, Cora M., Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Lasa, Adrian, Zidan, Jamal, HEBON, Lee, Min Hyuk, Bonanni, Bernardo, Zorn, Kristin K., Selkirk, Christina G. Hutten, Hulick, Peter J., Chenevix-Trench, Georgia, Abugattas, Julio, Spurdle, Amanda B., Antoniou, Antonis C., Lasset, Christine, Nathanson, Katherine L., Sukiennicki, Grzegorz, Adlard, Julian, Agata, Simona, Bradbury, Angela R., Henderson, Alex, Aittomäki, Kristiina, Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Couch, Fergus J., Ding, Yuan Chun, Arun, Branu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Brewer, Carole, Balmaña, Judith, Hentschel, Julia, Barile, Monica, Buecher, Bruno, Buys, Saundra S., Ditsch, Nina, Lázaro, Conxi, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Rantala, Johanna, Honisch, Ellen, Chiquette, Jocelyne, Chung, Wendy K., Domchek, Susan M., Claes, Kathleen B., Lee, Annette T., Collée, J. Margriet, Evans, D. Gareth, Dorfling, Cecilia M., Velázquez Pérez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Rhiem, Kerstin, Easton, Douglas F., Eeles, Ros, Sutter, Christian, Schmidt, Ane Y., Imyanitov, Evgeny N., Ehrencrona, Hans, Ejlertsen, Bent, EMBRACE, Engel, Christoph, Engert, Stefanie, Faivre, Laurence, Feliubadaló, Lidia, Robson, Mark, szabo, Csilla I., Tan, Yen Y., Fert Ferrer, Sandra, Barkardottir, Rosa B., Foretova, Lenka, Fowler, Jeffrey, Isaacs, Claudine, Frost, Debra, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Teixeira, Manuel R., Gehrig, Andrea, Rodriguez, Gustavo C., Lester, Jenny, GEMO Study Collaborators, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Izat, Louise, Giraud, Sophie, Glendon, Gord, Terry, Mary Beth, Godwin, Andrew K., Izquierdo, Angel, Jakubowska, Anna, Lesueur, Fabienne, Rogers, Mark T., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Gutierrez-Barrera, Angelica, Chan, T. L., Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Liljegren, Annelie, KConFab Investigators, Rudaitis, Vilius, Kim, Sung-Won, Lindor, Noralane M., Longy, Michel, Teulé, Alex, Loud, Jennifer T., Lu, Karen H., Goldgar, David E., Lubinski, Jan, Machackova, Eva, Barrowdale, Daniel, Rensburg, Elizabeth J. van, Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzaz, Cristina, Parsons, Michael T., and Matrai, Zoltan

Abstract

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

Published
2018

45. The Global State of the Genetic Counseling Profession

Author

Abacan, MaryAnn, primary, Alsubaie, Lamia, additional, Barlow-Stewart, Kristine, additional, Caanen, Beppy, additional, Cordier, Christophe, additional, Courtney, Eliza, additional, Davoine, Emeline, additional, Edwards, Janice, additional, Elackatt, Niby J., additional, Gardiner, Kate, additional, Guan, Yue, additional, Huang, Lian-Hua, additional, Malmgren, Charlotta Ingvoldstad, additional, Kejriwal, Sahil, additional, Kim, Hyon J., additional, Lambert, Deborah, additional, Lantigua-Cruz, Paulina Araceli, additional, Lee, Juliana M. H., additional, Lodahl, Marianne, additional, Lunde, Åshild, additional, Macaulay, Shelley, additional, Macciocca, Ivan, additional, Margarit, Sonia, additional, Middleton, Anna, additional, Moldovan, Ramona, additional, Ngeow, Joanne, additional, Obregon-Tito, Alexandra J., additional, Ormond, Kelly E., additional, Paneque, Milena, additional, Powell, Karen, additional, Sanghavi, Kunal, additional, Scotcher, Diana, additional, Scott, Jenna, additional, Juhé, Clara Serra, additional, Shkedi-Rafid, Shiri, additional, Wessels, Tina-Marié, additional, Yoon, Sook-Yee, additional, and Wicklund, Catherine, additional

Published
2018
Full Text
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46. A case-control study of breast cancer risk factors in 7,663 women in Malaysia

Author

Tan, Min-Min, primary, Ho, Weang-Kee, additional, Yoon, Sook-Yee, additional, Mariapun, Shivaani, additional, Hasan, Siti Norhidayu, additional, Lee, Daphne Shin-Chi, additional, Hassan, Tiara, additional, Lee, Sheau-Yee, additional, Phuah, Sze-Yee, additional, Sivanandan, Kavitta, additional, Ng, Patsy Pei-Sze, additional, Rajaram, Nadia, additional, Jaganathan, Maheswari, additional, Jamaris, Suniza, additional, Islam, Tania, additional, Rahmat, Kartini, additional, Fadzli, Farhana, additional, Vijayananthan, Anushya, additional, Rajadurai, Pathmanathan, additional, See, Mee-Hong, additional, Thong, Meow-Keong, additional, Mohd Taib, Nur Aishah, additional, Yip, Cheng-Har, additional, and Teo, Soo-Hwang, additional

Published
2018
Full Text
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47. Abstract 1420: Prevalence ofPALB2mutations in an unselected cohort of breast cancer patients and unaffected individuals from Malaysia and Singapore

Author

Ng, Patsy P., primary, Wen, Wei Xiong, additional, Wijaya, Eldarina, additional, Allen, Jamie, additional, Lim, Joanna, additional, Lau, Shao Yan, additional, Decker, Brennan, additional, Pooley, Karen, additional, Dorling, Leila, additional, Luccarini, Craig, additional, Baynes, Caroline, additional, Conroy, Don, additional, Harrington, Patricia, additional, Mariapun, Shivaani, additional, Hasan, Siti Norhidayu, additional, Lee, Daphne Shin-Chin, additional, Lee, Sheau Yee, additional, Yoon, Sook Yee, additional, Yip, Cheng Har, additional, Taib, Nur Aishah, additional, Ho, Weang Kee, additional, Hartman, Mikael, additional, Antoniou, Antonis C, additional, Dunning, Alison M, additional, Easton, Douglas F, additional, and Teo, Soo Hwang, additional

Published
2018
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48. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

Author

Lecarpentier, Julie, Silvestri, Valentina, Kuchenbaecker, Karoline B., Barrowdale, Daniel, Dennis, Joe, McGuffog, Lesley, Soucy, Penny, Leslie, Goska, Rizzolo, Piera, Navazio, Anna Sara, Valentini, Virginia, Zelli, Veronica, Lee, Andrew, Al Olama, Ali Amin, Tyrer, Jonathan P., Southey, Melissa, John, Esther M., Conner, Thomas A., Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Steele, Linda, Ding, Yuan Chun, Neuhausen, Susan L., Hansen, Thomas V. O., Osorio, Ana, Weitzel, Jeffrey N., Toss, Angela, Medici, Veronica, Cortesi, Laura, Zanna, Ines, Palli, Domenico, Radice, Paolo, Manoukian, Siranoush, Peissel, Bernard, Azzollini, Jacopo, Viel, Alessandra, Cini, Giulia, Damante, Giuseppe, Tommasi, Stefania, Peterlongo, Paolo, Fostira, Florentia, Hamann, Ute, Evans, D. Gareth, Henderson, Alex, Brewer, Carole, Eccles, Diana, Cook, Jackie, Ong, Kai-ren, Walker, Lisa, Side, Lucy E., Porteous, Mary E., Davidson, Rosemarie, Hodgson, Shirley, Frost, Debra, Adlard, Julian, Izatt, Louise, Eeles, Ros, Ellis, Steve, Tischkowitz, Marc, Godwin, Andrew K., Meindl, Alfons, Gehrig, Andrea, Dworniczak, Bernd, Sutter, Christian, Engel, Christoph, Niederacher, Dieter, Steinemann, Doris, Hahnen, Eric, Hauke, Jan, Rhiem, Kerstin, Kast, Karin, Arnold, Norbert, Ditsch, Nina, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Wand, Dorothea, Lasset, Christine, Stoppa-Lyonnet, Dominique, Belotti, Muriel, Damiola, Francesca, Barjhoux, Laure, Mazoyer, Sylvie, Van Heetvelde, Mattias, Poppe, Bruce, De Leeneer, Kim, Claes, Kathleen B. M., de la Hoya, Miguel, Garcia-Barberan, Vanesa, Caldes, Trinidad, Perez Segura, Pedro, Kiiski, Johanna I., Aittomaeki, Kristiina, Khan, Sofia, Nevanlinna, Heli, van Asperen, Christi J., Vaszko, Tibor, Kasler, Miklos, Olah, Edith, Balmana, Judith, Gutierrez-Enriquez, Sara, Diez, Orland, Teule, Alex, Izquierdo, Angel, Darder, Esther, Brunet, Joan, Del Valle, Jesus, Feliubadalo, Lidia, Pujana, Miquel Angel, Lazaro, Conxi, Arason, Adalgeir, Agnarsson, Bjarni A., Johannsson, Oskar Th., Barkardottir, Rosa B., Alducci, Elisa, Tognazzo, Silvia, Montagna, Marco, Teixeira, Manuel R., Pinto, Pedro, Spurdle, Amanda B., Holland, Helene, Lee, Jong Won, Lee, Min Hyuk, Lee, Jihyoun, Kim, Sung-Won, Kang, Eunyoung, Kim, Zisun, Sharma, Priyanka, Rebbeck, Timothy R., Vijai, Joseph, Robson, Mark, Lincoln, Anne, Musinsky, Jacob, Gaddam, Pragna, Tan, Yen Y., Berger, Andreas, Singer, Christian F., Loud, Jennifer T., Greene, Mark H., Mulligan, Anna Marie, Glendon, Gord, Andrulis, Irene L., Toland, Amanda Ewart, Senter, Leigha, Bojesen, Anders, Nielsen, Henriette Roed, Skytte, Anne-Bine, Sunde, Lone, Jensen, Uffe Birk, Pedersen, Inge Sokilde, Krogh, Lotte, Kruse, Torben A., Caligo, Maria A., Yoon, Sook-Yee, Teo, Soo-Hwang, von Wachenfeldt, Anna, Huo, Dezheng, Nielsen, Sarah M., Olopade, Olufunmilayo I., Nathanson, Katherine L., Domchek, Susan M., Lorenchick, Christa, Jankowitz, Rachel C., Campbell, Ian, James, Paul, Mitchell, Gillian, Orr, Nick, Park, Sue Kyung, Thomassen, Mads, Offit, Kenneth, Couch, Fergus J., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Schmutzler, Rita K., Antoniou, Antonis C., Ottini, Laura, Lecarpentier, Julie, Silvestri, Valentina, Kuchenbaecker, Karoline B., Barrowdale, Daniel, Dennis, Joe, McGuffog, Lesley, Soucy, Penny, Leslie, Goska, Rizzolo, Piera, Navazio, Anna Sara, Valentini, Virginia, Zelli, Veronica, Lee, Andrew, Al Olama, Ali Amin, Tyrer, Jonathan P., Southey, Melissa, John, Esther M., Conner, Thomas A., Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Steele, Linda, Ding, Yuan Chun, Neuhausen, Susan L., Hansen, Thomas V. O., Osorio, Ana, Weitzel, Jeffrey N., Toss, Angela, Medici, Veronica, Cortesi, Laura, Zanna, Ines, Palli, Domenico, Radice, Paolo, Manoukian, Siranoush, Peissel, Bernard, Azzollini, Jacopo, Viel, Alessandra, Cini, Giulia, Damante, Giuseppe, Tommasi, Stefania, Peterlongo, Paolo, Fostira, Florentia, Hamann, Ute, Evans, D. Gareth, Henderson, Alex, Brewer, Carole, Eccles, Diana, Cook, Jackie, Ong, Kai-ren, Walker, Lisa, Side, Lucy E., Porteous, Mary E., Davidson, Rosemarie, Hodgson, Shirley, Frost, Debra, Adlard, Julian, Izatt, Louise, Eeles, Ros, Ellis, Steve, Tischkowitz, Marc, Godwin, Andrew K., Meindl, Alfons, Gehrig, Andrea, Dworniczak, Bernd, Sutter, Christian, Engel, Christoph, Niederacher, Dieter, Steinemann, Doris, Hahnen, Eric, Hauke, Jan, Rhiem, Kerstin, Kast, Karin, Arnold, Norbert, Ditsch, Nina, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Wand, Dorothea, Lasset, Christine, Stoppa-Lyonnet, Dominique, Belotti, Muriel, Damiola, Francesca, Barjhoux, Laure, Mazoyer, Sylvie, Van Heetvelde, Mattias, Poppe, Bruce, De Leeneer, Kim, Claes, Kathleen B. M., de la Hoya, Miguel, Garcia-Barberan, Vanesa, Caldes, Trinidad, Perez Segura, Pedro, Kiiski, Johanna I., Aittomaeki, Kristiina, Khan, Sofia, Nevanlinna, Heli, van Asperen, Christi J., Vaszko, Tibor, Kasler, Miklos, Olah, Edith, Balmana, Judith, Gutierrez-Enriquez, Sara, Diez, Orland, Teule, Alex, Izquierdo, Angel, Darder, Esther, Brunet, Joan, Del Valle, Jesus, Feliubadalo, Lidia, Pujana, Miquel Angel, Lazaro, Conxi, Arason, Adalgeir, Agnarsson, Bjarni A., Johannsson, Oskar Th., Barkardottir, Rosa B., Alducci, Elisa, Tognazzo, Silvia, Montagna, Marco, Teixeira, Manuel R., Pinto, Pedro, Spurdle, Amanda B., Holland, Helene, Lee, Jong Won, Lee, Min Hyuk, Lee, Jihyoun, Kim, Sung-Won, Kang, Eunyoung, Kim, Zisun, Sharma, Priyanka, Rebbeck, Timothy R., Vijai, Joseph, Robson, Mark, Lincoln, Anne, Musinsky, Jacob, Gaddam, Pragna, Tan, Yen Y., Berger, Andreas, Singer, Christian F., Loud, Jennifer T., Greene, Mark H., Mulligan, Anna Marie, Glendon, Gord, Andrulis, Irene L., Toland, Amanda Ewart, Senter, Leigha, Bojesen, Anders, Nielsen, Henriette Roed, Skytte, Anne-Bine, Sunde, Lone, Jensen, Uffe Birk, Pedersen, Inge Sokilde, Krogh, Lotte, Kruse, Torben A., Caligo, Maria A., Yoon, Sook-Yee, Teo, Soo-Hwang, von Wachenfeldt, Anna, Huo, Dezheng, Nielsen, Sarah M., Olopade, Olufunmilayo I., Nathanson, Katherine L., Domchek, Susan M., Lorenchick, Christa, Jankowitz, Rachel C., Campbell, Ian, James, Paul, Mitchell, Gillian, Orr, Nick, Park, Sue Kyung, Thomassen, Mads, Offit, Kenneth, Couch, Fergus J., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Schmutzler, Rita K., Antoniou, Antonis C., and Ottini, Laura

Abstract

PurposeBRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigatedfor the first time to our knowledgeassociations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction.Materials and MethodsWe genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights.ResultsIn male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 x 10(-6)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 x 10(-9)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively.ConclusionPRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

Published
2017

49. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Author

Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji Yeob, Claes, Kathleen B M, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B L, Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, De La Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F A G, Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen Yang, Shu, Xiao Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu Chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, Van Den Ouweland, Ans M W, Van Doorn, Helena C., Van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook Yee, Yu, Jyh Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Gayther, Simon A., Bowtell, David, DeFazio, Anna, Webb, Penny, Collonge-Rame, Marie Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, De Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-De-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Rookus, M. A., Van Leeuwen, F. E., Van Der Kolk, L. E., Schmidt, M. K., Russell, N. S., De Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., Van Deurzen, C. H M, Obdeijn, I. M., Van Asperen, C. J., Tollenaar, R. A E M, Van Cronenburg, T. C T E F, Kets, C. M., Ausems, M. G E M, Van Der Pol, C. C., Van Os, T. A M, Waisfisz, Q., Meijers-Heijboer, H. E J, Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., De Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I H, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Breast Cancer Research Trust, Instituto de Salud Carlos III, Lon V. Smith Foundation, Federal Ministry of Education & Research (Alemania), Finlands Akademi (Finlandia), United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Canadian Institutes of Health Research, Ministère de Économie, Innovation et Exportation (Canadá), Ministry of Higher Education (Malasia), National Medical Research Council (Singapur), University of Oulu (Finlandia), Yorkshire Cancer Research, Hellenic Cooperative Oncology Group, California Cancer Research Program, Danish Cancer Society, Ministry of Science and Higher Education (Polonia), Asociación Española Contra el Cáncer, University of Kansas. Cancer Center (Estados Unidos), Hungarian Research Grants, Norwegian EEA Financial Mechanism, Canadian Breast Cancer Network, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Congressionally Directed Medical Research Programs (Estados Unidos), NRG Oncology National (Estados Unidos), Unión Europea. 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Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. 134 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. 135 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, 70210 Kuopio, Finland. 136 Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland. 137 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland. 138 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, 1478 Oslo, Norway. 139 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. 140 Department of Surgery, The University of Hong Kong, Hong Kong, China. 141Vesalius Research Center, VIB, 3000 Leuven, Belgium. 142 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, 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Houston, Texas 77030, USA. 162 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA. 163 Department of Medicine and Genetics, University of California, San Francisco, California 94143, USA. 164 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 165 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 166 Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary. 167 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA. 168 The Ohio State University and the James Cancer Center, Columbus, Ohio 43210, USA. 169 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York 10017, USA. 170 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28019 Madrid, Spain. 171 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain. 172 Department of Surgery, Seoul National University College of Medicine, Seoul, 03080 Korea. 173 Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. 174 Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. 175 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, 16 20139 Milan, Italy. 176 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. 177 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida 33606, USA. 178 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 179 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 180 Laboratory of Cancer Genetics and Tumour Biology, Northern Finland 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Norway. 24 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland. 25 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. 26 International Epidemiology Institute, Rockville, Maryland 20850, USA. 27 Gynaecology Research Unit, Hannover Medical School, Hannover D-30625, Germany. 28 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark. 29 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. 30 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 31 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 32 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo N-0310, Norway. 33 K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0310, Norway. 34 Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart D-70376, Germany. 35 University of Tu¨bingen, Tu¨bingen 72074, Germany. 36 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 37 International Agency for Research on Cancer, Lyon 69008, France. 38 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 39 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. 40 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d’Investigacio´ Biome`dica de Girona), Catalan Institute of Oncology, Girona 08908, Spain. 41 Department of Surgery, National University Health System, Singapore 119077, Singapore. 42 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 43 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany. 44 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029 HUS, Finland. 45 Department of Pathology, Helsinki University Central Hospital, Helsinki 00029, Finland. 46 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. 47 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacio´n Sanitaria del Hospital Clı ´nico San Carlos), Madrid 28040, Spain. 48 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 49 Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo 14263, New York, USA. 50 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 51 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany. 52 Unite´ de recherche en sante´ des populations, Centre des maladies du sein Descheˆnes-Fabia, Centre de recherche FRSQ du Centre hospitalier affilie´ universitaire de Que´bec, Que´bec City, Que´bec Canada, G1J 1Z4. 53 Cancer Research Institute, Seoul National University, Seoul 08826, Korea. 54 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 55 Center for Medical Genetics, Ghent University, Ghent 9000, Belgium. 56 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. 57 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield S10 2TN, UK. 58 Harvard HT Chan School of Public Health, Boston, Massachusetts 02115, USA. 59 Obstetrics and Gynecology Epidemiology Center, Brigham andWomen’s Hospital and Harvard Medical 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Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. 233Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. 234 Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. 235 Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. 236 Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. 237 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia. 238 Department of Gynaecological Oncology, Westmead Institute for Cancer Research, Westmead Hospital Westmead, New South Wales 2145, Australia., Tyrer, Jonathan [0000-0003-3724-4757], Dennis, Joe [0000-0003-4591-1214], Rhenius, Valerie [0000-0003-4215-3235], Song, Honglin [0000-0001-5076-7371], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Quality of care, Anesthesiology, Human genetics, CCA - Cancer biology, and VU University medical center

Subjects
endocrine system diseases, Messenger, IDENTIFIES 3, MODIFIERS, Brjóstakrabbamein, BRCA2 MUTATION CARRIERS, Medicine and Health Sciences, GWAS, INVESTIGATORS, African Continental Ancestry Group, Asian Continental Ancestry Group, Breast Neoplasms, Chromosomes, Human, Pair 19, Female, Genome-Wide Association Study, Genotype, Humans, Ovarian Neoplasms, RNA, Messenger, Alleles, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, skin and connective tissue diseases, COMMON VARIANTS, EPITHELIAL-CELLS, Single Nucleotide, female genital diseases and pregnancy complications, NAF12, Medical Genetics, Human, endocrine system, Science, Chromosomes, Human, Pair 19/genetics, Black People, Breast Neoplasms/genetics, Chromosomes, Article, Ovarian Neoplasms/genetics, SDG 3 - Good Health and Well-being, Asian People, REVEALS, Polymorphism, GENOME-WIDE ASSOCIATION, Krabbamein, Medicinsk genetik, Cancer och onkologi, Pair 19, Arfgengi, GENE, Eggjastokkar, Cancer and Oncology, RNA, BRCA1 Protein/genetics
Abstract

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P, A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Published
2016

50. Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia

Author

Wen, Wei Xiong, primary, Allen, Jamie, additional, Lai, Kah Nyin, additional, Mariapun, Shivaani, additional, Hasan, Siti Norhidayu, additional, Ng, Pei Sze, additional, Lee, Daphne Shin-Chi, additional, Lee, Sheau Yee, additional, Yoon, Sook-Yee, additional, Lim, Joanna, additional, Lau, Shao Yan, additional, Decker, Brennan, additional, Pooley, Karen, additional, Dorling, Leila, additional, Luccarini, Craig, additional, Baynes, Caroline, additional, Conroy, Don M, additional, Harrington, Patricia, additional, Simard, Jacques, additional, Yip, Cheng Har, additional, Mohd Taib, Nur Aishah, additional, Ho, Weang Kee, additional, Antoniou, Antonis C, additional, Dunning, Alison M, additional, Easton, Douglas F, additional, and Teo, Soo Hwang, additional

Published
2017
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