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1. Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated “Big Bang” pathway to CRC in three of the four Lynch syndromes

Author

Møller, Pål, Haupt, Saskia, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., Sunde, Lone, Seppälä, Toni, Burn, John, Bernstein, Inge, Capella, Gabriel, Evans, D. Gareth, Lindblom, Annika, Winship, Ingrid, Macrae, Finlay, Katz, Lior, Laish, Ido, Vainer, Elez, Monahan, Kevin, Half, Elizabeth, Horisberger, Karoline, da Silva, Leandro Apolinário, Heuveline, Vincent, Therkildsen, Christina, Lautrup, Charlotte, Klarskov, Louise L, Cavestro, Giulia Martina, Möslein, Gabriela, Hovig, Eivind, and Dominguez-Valentin, Mev

Published
2024
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3. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

Author

Hakkaart, Christopher, Pearson, John F, Marquart, Louise, Dennis, Joe, Wiggins, George AR, Barnes, Daniel R, Robinson, Bridget A, Mace, Peter D, Aittomäki, Kristiina, Andrulis, Irene L, Arun, Banu K, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Belhadj, Sami, Berger, Lieke, Blok, Marinus J, Boonen, Susanne E, Borde, Julika, Bradbury, Angela R, Brunet, Joan, Buys, Saundra S, Caligo, Maria A, Campbell, Ian, Chung, Wendy K, Claes, Kathleen BM, Collonge-Rame, Marie-Agnès, Cook, Jackie, Cosgrove, Casey, Couch, Fergus J, Daly, Mary B, Dandiker, Sita, Davidson, Rosemarie, de la Hoya, Miguel, de Putter, Robin, Delnatte, Capucine, Dhawan, Mallika, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Easton, Douglas F, Ehrencrona, Hans, Engel, Christoph, Evans, D Gareth, Faust, Ulrike, Feliubadaló, Lidia, Fostira, Florentia, Friedman, Eitan, Frone, Megan, Frost, Debra, Garber, Judy, Gayther, Simon A, Gehrig, Andrea, Gesta, Paul, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Hahnen, Eric, Hake, Christopher R, Hamann, Ute, Hansen, Thomas VO, Hauke, Jan, Hentschel, Julia, Herold, Natalie, Honisch, Ellen, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul A, Janavicius, Ramunas, John, Esther M, Joseph, Vijai, Karlan, Beth Y, Kemp, Zoe, Kirk, Judy, Konstantopoulou, Irene, Koudijs, Marco, Kwong, Ava, Laitman, Yael, Lalloo, Fiona, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Legrand, Clémentine, Leslie, Goska, Lesueur, Fabienne, Mai, Phuong L, Manoukian, Siranoush, Mari, Véronique, Martens, John WM, McGuffog, Lesley, Mebirouk, Noura, Meindl, Alfons, Miller, Austin, and Montagna, Marco

Subjects
Human Genome, Prevention, Breast Cancer, Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Heterozygote, Humans, RNA, Messenger, GEMO Study Collaborators, EMBRACE Collaborators, SWE-BRCA Investigators, kConFab Investigators, HEBON Investigators
Abstract

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

Published
2022

6. Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated 'Big Bang' pathway to CRC in three of the four Lynch syndromes

Author

Maller, Pål, Haupt, Saskia, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., Sunde, Lone, Seppälä, Toni, Burn, John, Bernstein, Inge, Capella, Gabriel, Evans, D. Gareth, Lindblom, Annika, Winship, Ingrid, Macrae, Finlay, Katz, Lior, Laish, Ido, Vainer, Elez, Monahan, Kevin, Half, Elizabeth, Horisberger, Karoline, da Silva, Leandro Apolinário, Heuveline, Vincent, Therkildsen, Christina, Lautrup, Charlotte, Klarskov, Louise L, Cavestro, Giulia Martina, Möslein, Gabriela, Hovig, Eivind, and Dominguez-Valentin, Mev

Subjects
EPUB (Standard), Colonoscopy -- Analysis, Health
Abstract

Background Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. Materials and methods We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. Results Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. Conclusions Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports. Keywords: MSI, MLH1, MSH2, MSH6, PMS2, dMMR, Lynch syndromes, Colorectal, cancer, Adenoma, Colonoscopy, Sojourn time, Author(s): Pål Maller[sup.1], Saskia Haupt[sup.2,3], Aysel Ahadova[sup.4,5], Matthias Kloor[sup.4,5], Julian R. Sampson[sup.6], Lone Sunde[sup.7,8,9], Toni Seppälä[sup.10,11,12], John Burn[sup.13], Inge Bernstein[sup.14,15], Gabriel Capella[sup.16], D. Gareth Evans[sup.17], Annika Lindblom[sup.18,19], Ingrid Winship[sup.20,21], Finlay [...]

Published
2024
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7. National clinical Genetic Networks - GENets - Establishment of expert collaborations in Denmark

Author

Lildballe, Dorte L., Frederiksen, Anja Lisbeth, Schönewolf-Greulich, Bitten, Brasch-Andersen, Charlotte, Lautrup, Charlotte Kvist, Karstensen, Helena Gásdal, Pedersen, Inge Søkilde, Sunde, Lone, Risom, Lotte, Rasmussen, Maria, Bertelsen, Mette, Andersen, Mette Klarskov, Rendtorff, Nanna Dahl, Gregersen, Pernille Axél, Tørring, Pernille M., Hammer-Hansen, Sophia, Boonen, Susanne E., Lindquist, Suzanne Granhøj, Hammer, Trine Bjørg, and Diness, Birgitte R.

Published
2023
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10. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Møller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubiński, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Dębniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueñas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.

Published
2022
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11. Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated “Big Bang” pathway to CRC in three of the four Lynch syndromes

Author

Møller, Pål, primary, Haupt, Saski, additional, Ahadova, Aysel, additional, Kloor, Matthias, additional, Sampson, Julian, additional, Sunde, Lone, additional, Seppälä, Toni Toni, additional, Burn, John, additional, Bernstein, Inge, additional, Capella, Gabriel, additional, Evans, D Gareth, additional, Lindblom, Annika, additional, Winship, Ingrid, additional, Macrae, Finlay, additional, Katz, Lior, additional, Laish, Ido, additional, Vainer, Elez, additional, Monahan, Kevin, additional, Half, Elizabeth, additional, Horisberger, Karoline, additional, Silva, Leandro Apolinário da, additional, Heuveline, Vincent, additional, Therkildsen, Christina, additional, Lautrup, Charlotte, additional, Klarskov, Louvise L, additional, Cavestro, Giulia Martina, additional, Möslein, Gabriela, additional, Hovig, Eivind, additional, and Dominguez-Valentin, Mev, additional

Published
2024
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13. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Author

Win, Aung Ko, Dowty, James G., Reece, Jeanette C., Lee, Grant, Templeton, Allyson S., Plazzer, John-Paul, Buchanan, Daniel D., Akagi, Kiwamu, Aksoy, Seçil, Alonso, Angel, Alvarez, Karin, Amor, David J., Ankathil, Ravindran, Aretz, Stefan, Arnold, Julie L., Aronson, Melyssa, Austin, Rachel, Backman, Ann-Sofie, Bajwa-ten Broeke, Sanne W., Barca-Tierno, Verónica, Barwell, Julian, Bernstein, Inge, Berthet, Pascaline, Betz, Beate, Bignon, Yves-Jean, Boisjoli, Talya, Bonadona, Valérie, Briollais, Laurent, Brunet, Joan, Bucksch, Karolin, Buecher, Bruno, Buettner, Reinhard, Burn, John, Caldés, Trinidad, Capella, Gabriel, Caron, Olivier, Casey, Graham, Chew, Min H., Choi, Yun-hee, Church, James, Clendenning, Mark, Colas, Chrystelle, Cops, Elisa J., Coupier, Isabelle, Cruz-Correa, Marcia, de la Chapelle, Albert, de Wind, Niels, Dębniak, Tadeusz, Della Valle, Adriana, Delnatte, Capuccine, Dhooge, Marion, Dominguez-Valentin, Mev, Drouet, Youenn, Duijkers, Floor A., Engel, Christoph, Esperon, Patricia, Evans, D. Gareth, Falcón de Vargas, Aída, Figueiredo, Jane C, Foulkes, William, Fourme, Emmanuelle, Frebourg, Thierry, Gallinger, Steven, Garre, Pilar, Genuardi, Maurizio, Gerdes, Anne-Marie, Gima, Lauren M., Giraud, Sophie, Goodwin, Annabel, Görgens, Heike, Green, Kate, Guillem, Jose, Guillén-Ponce, Carmen, Guimbaud, Roselyne, Guindalini, Rodrigo S.C., Half, Elizabeth E., Hall, Michael J, Hampel, Heather, Hansen, Thomas V.O., Heinimann, Karl, Hes, Frederik J., Hill, James, Ho, Judy W.C., Holinski-Feder, Elke, Hoogerbrugge, Nicoline, Hüneburg, Robert, Huntley, Vanessa, James, Paul A., Jensen, Uffe B, John, Thomas, Juhari, Wan K.W., Kalady, Matthew, Kastrinos, Fay, Kloor, Matthias, Kohonen-Corish, Maija RJ, Krogh, Lotte N., Kupfer, Sonia S., Ladabaum, Uri, Lagerstedt-Robinson, Kristina, Lalloo, Fiona, Lasset, Christine, Latchford, Andrew, Laurent-Puig, Pierre, Lautrup, Charlotte K., Leggett, Barbara A., Lejeune, Sophie, LeMarchand, Loic, Ligtenberg, Marjolijn, Lindor, Noralane, Loeffler, Markus, Longy, Michel, Lopez, Francisco, Lowery, Jan, Lubiński, Jan, Lucassen, Anneke M, Lynch, Patrick M., Malińska, Karolina, Matsubara, Nagahide, Mecklin, Jukka-Pekka, Møller, Pål, Monahan, Kevin, Morrison, Patrick J., Nattermann, Jacob, Navarro, Matilde, Neffa, Florencia, Neklason, Deborah, Newcomb, Polly A., Ngeow, Joanne, Nichols, Cassandra, Nielsen, Maartje, Nixon, Dawn M., Nogues, Catherine, Okkels, Henrik, Olschwang, Sylviane, Pachter, Nicholas, Pai, Rish K., Palmero, Edenir I., Pande, Mala, Parry, Susan, Patel, Swati G., Pearlman, Rachel, Perne, Claudia, Pineda, Marta, Poplawski, Nicola K, Pylvänäinen, Kirsi, Qiu, Jay, Rahner, Nils, Ramesar, Raj, Rasmussen, Lene J., Redler, Silke, Reis, Rui M., Ricciardiello, Luigi, Rogoża-Janiszewska, Emilia, Rosty, Christophe, Samadder, N. Jewel, Sampson, Julian R., Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Schuster, Helène, Scott, Rodney, Senter, Leigha, Seppälä, Toni T, Shtoyerman, Rakefet, Sijmons, Rolf H., Snyder, Carrie, Solomon, Ilana B., Soto, Jose Luis, Southey, Melissa C., Spigelman, Allan, Spirandelli, Florencia, Spurdle, Amanda B., Steinke-Lange, Verena, Stoffel, Elena M., Strassburg, Christian P., Sunde, Lone, Susman, Rachel, Syngal, Sapna, Tanakaya, Kohji, Tezcan, Gülçin, Therkildsen, Christina, Thibodeau, Steve, Tomita, Naohiro, Tucker, Katherine M., Tunca, Berrin, Turchetti, Daniela, Uhrhammer, Nancy, Utsunomiya, Joji, Vaccaro, Carlos, van Duijnhoven, Fränzel J.B., van Wanzeele, Meghan J., Vangala, Deepak B., Vasen, Hans F.A., von Knebel Doeberitz, Magnus, von Salomé, Jenny, Wadt, Karin A.W., Ward, Robyn L., Weitz, Jürgen, Weitzel, Jeffrey N., Williams, Heinric, Winship, Ingrid, Wise, Paul E., Wods, Julie, Woods, Michael O., Yamaguchi, Tatsuro, Zachariae, Silke, Zahary, Mohd N., Hopper, John L., Haile, Robert W., Macrae, Finlay A., Möslein, Gabriela, and Jenkins, Mark A.

Published
2021
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15. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Maller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, LubiÅski, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, DÄbniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueéas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.

Subjects
EPUB (Standard) -- Comparative analysis, Colonoscopy -- Comparative analysis, Colorectal cancer -- Comparative analysis, Health
Abstract

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so. Keywords: Lynch Syndrome, Epidemiology, Prevention, Penetrance, Colorectal cancer, Segregation analysis, Prospective, Incidence, Over-diagnosis, Colonoscopy, Author(s): Pål Maller[sup.1], Toni Seppälä[sup.2,3,4], James G. Dowty[sup.5], Saskia Haupt[sup.6,7], Mev Dominguez-Valentin[sup.1], Lone Sunde[sup.8,9], Inge Bernstein[sup.10,11], Christoph Engel[sup.12], Stefan Aretz[sup.13], Maartje Nielsen[sup.14], Gabriel Capella[sup.15], Dafydd Gareth Evans[sup.16], John Burn[sup.17], Elke [...]

Published
2022
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18. Survival, surveillance, and genetics in patients with Peutz–Jeghers syndrome: A nationwide study

Author

Jelsig, Anne Marie, primary, van Overeem Hansen, Thomas, additional, Gede, Lene Bjerring, additional, Qvist, Niels, additional, Christensen, Lise‐Lotte, additional, Lautrup, Charlotte Kvist, additional, Frederiksen, Jane Hübertz, additional, Sunde, Lone, additional, Ousager, Lilian Bomme, additional, Ljungmann, Ken, additional, Bertelsen, Birgitte, additional, and Karstensen, John Gásdal, additional

Published
2023
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19. Whole genome sequencing and disease pattern in patients with juvenile polyposis syndrome:a nationwide study

Author

Jelsig, Anne Marie, van Overeem Hansen, Thomas, Gede, Lene Bjerring, Qvist, Niels, Christensen, Lise Lotte, Lautrup, Charlotte Kvist, Ljungmann, Ken, Christensen, Louise Torp, Rønlund, Karina, Tørring, Pernille Mathiesen, Bertelsen, Birgitte, Sunde, Lone, Karstensen, John Gásdal, Jelsig, Anne Marie, van Overeem Hansen, Thomas, Gede, Lene Bjerring, Qvist, Niels, Christensen, Lise Lotte, Lautrup, Charlotte Kvist, Ljungmann, Ken, Christensen, Louise Torp, Rønlund, Karina, Tørring, Pernille Mathiesen, Bertelsen, Birgitte, Sunde, Lone, and Karstensen, John Gásdal

Abstract

Juvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected in SMAD4 or BMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant in BMPR1A or SMAD4. In patients where no variant had been detected, we performed genetic analysis, including whole genome sequencing. We collected clinical information on all patients to investigate the phenotypic spectrum. Sixty-six patients (mean age 40 years) were included of whom the pathogenic variant was unknown in seven patients. We detected a pathogenic variant in SMAD4 or PTEN in additional three patients and thus ≈ 95% of patients had a pathogenic germline variant. Endoscopic information was available in fifty-two patients (79%) and of these 31 (60%) fulfilled the clinical criteria of JPS. In 41 patients (79%), other types of polyps than juvenile had been removed. Our results suggest that almost all patients with a clinical diagnosis of JPS has a pathogenic variant in mainly BMPR1A, SMAD4, and more rarely PTEN. However, not all patients with a pathogenic variant fulfil the clinical criteria of JPS. We also demonstrated a wide clinical spectrum, and that the histopathology of removed polyps varied.

Published
2023

20. Survival, surveillance, and genetics in patients with Peutz–Jeghers syndrome:A nationwide study

Author

Jelsig, Anne Marie, van Overeem Hansen, Thomas, Gede, Lene Bjerring, Qvist, Niels, Christensen, Lise Lotte, Lautrup, Charlotte Kvist, Frederiksen, Jane Hübertz, Sunde, Lone, Ousager, Lilian Bomme, Ljungmann, Ken, Bertelsen, Birgitte, Karstensen, John Gásdal, Jelsig, Anne Marie, van Overeem Hansen, Thomas, Gede, Lene Bjerring, Qvist, Niels, Christensen, Lise Lotte, Lautrup, Charlotte Kvist, Frederiksen, Jane Hübertz, Sunde, Lone, Ousager, Lilian Bomme, Ljungmann, Ken, Bertelsen, Birgitte, and Karstensen, John Gásdal

Abstract

Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed., Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.

Published
2023

21. Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrome database report

Author

Seppälä, Toni T., Ahadova, Aysel, Dominguez-Valentin, Mev, Macrae, Finlay, Evans, D. Gareth, Therkildsen, Christina, Sampson, Julian, Scott, Rodney, Burn, John, Möslein, Gabriela, Bernstein, Inge, Holinski-Feder, Elke, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Lautrup, Charlotte Kvist, Lindblom, Annika, Plazzer, John-Paul, Winship, Ingrid, Tjandra, Douglas, Katz, Lior H., Aretz, Stefan, Hüneburg, Robert, Holzapfel, Stefanie, Heinimann, Karl, Valle, Adriana Della, Neffa, Florencia, Gluck, Nathan, de Vos tot Nederveen Cappel, Wouter H., Vasen, Hans, Morak, Monika, Steinke-Lange, Verena, Engel, Christoph, Rahner, Nils, Schmiegel, Wolff, Vangala, Deepak, Thomas, Huw, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Capella, Gabriel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, ten Broeke, Sanne, Nielsen, Maartje, Ljungmann, Ken, Nakken, Sigve, Lindor, Noralane, Frayling, Ian, Hovig, Eivind, Sunde, Lone, Kloor, Matthias, Mecklin, Jukka-Pekka, Kalager, Mette, and Møller, Pål

Published
2019
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23. Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Author

Li, Hongyan, primary, Engel, Christoph, additional, Hoya, Miguel de la, additional, Peterlongo, Paolo, additional, Yannoukakos, Drakoulis, additional, Livraghi, Luca, additional, Radice, Paolo, additional, Thomassen, Mads, additional, Hansen, Thomas V.O., additional, Gerdes, Anne-Marie, additional, Nielsen, Henriette R., additional, Caputo, Sandrine M., additional, Zambelli, Alberto, additional, Borg, Ake, additional, Solano, Angela, additional, Thomas, Abigail, additional, Parsons, Michael T., additional, Antoniou, Antonis C., additional, Leslie, Goska, additional, Yang, Xin, additional, Chenevix-Trench, Georgia, additional, Caldes, Trinidad, additional, Kwong, Ava, additional, Pedersen, Inge Søkilde, additional, Lautrup, Charlotte K., additional, John, Esther M., additional, Terry, Mary Beth, additional, Hopper, John L., additional, Southey, Melissa C., additional, Andrulis, Irene L., additional, Tischkowitz, Marc, additional, Janavicius, Ramunas, additional, Boonen, Susanne E., additional, Kroeldrup, Lone, additional, Varesco, Liliana, additional, Hamann, Ute, additional, Vega, Ana, additional, Palmero, Edenir I., additional, Garber, Judy, additional, Montagna, Marco, additional, Van Asperen, Christi J., additional, Foretova, Lenka, additional, Greene, Mark H., additional, Selkirk, Tina, additional, Moller, Pal, additional, Toland, Amanda E., additional, Domchek, Susan M., additional, James, Paul A., additional, Thorne, Heather, additional, Eccles, Diana M., additional, Nielsen, Sarah M., additional, Manoukian, Siranoush, additional, Pasini, Barbara, additional, Caligo, Maria A., additional, Lazaro, Conxi, additional, Kirk, Judy, additional, Wappenschmidt, Barbara, additional, Spurdle, Amanda B., additional, Couch, Fergus J., additional, Schmutzler, Rita, additional, and Goldgar, David E., additional

Published
2022
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24. Telomere biology disorders

Author

Byrjalsen, Anna, Bygum, Anette, Lautrup, Charlotte Kvist, Frederiksen, Anja Lisbeth, Fialla, Annette Dam, Raaschou-Jensen, Klas, Bendstrup, Elisabeth, Madsen, Tania Nicole, Klarskov, Mette, and Jelsig, Anne Marie

Subjects
Adult, Vagus Nerve Stimulation, Epilepsy/therapy, Humans, Telomere, Child, Diet, Ketogenic, Biology
Abstract

This review finds that, in children and adults with epilepsy, there are several treatment options. Multiple antiseizure medications are available and in case of drug-resistant epilepsy, a non-pharmacological approach is recommended, including epilepsy surgery, vagus nerve stimulation, or ketogenic diet treatment. The aim of the treatment is to avoid further seizures, but also to avoid negative cognitive, psychological, and social consequences of epilepsy.

Published
2022

25. Telomersygdomme

Author

Byrjalsen, Anna, Bygum, Anette, Lautrup, Charlotte Kvist, Frederiksen, Anja Lisbeth, Fialla, Annette Dam, Raaschou-Jensen, Klas, Bendstrup, Elisabeth, Madsen, Tania Nicole, Klarskov, Mette, and Jelsig, Anne Marie

Abstract

This review finds that, in children and adults with epilepsy, there are several treatment options. Multiple antiseizure medications are available and in case of drug-resistant epilepsy, a non-pharmacological approach is recommended, including epilepsy surgery, vagus nerve stimulation, or ketogenic diet treatment. The aim of the treatment is to avoid further seizures, but also to avoid negative cognitive, psychological, and social consequences of epilepsy.

Published
2022

26. Distinct gastric phenotype in patients with pathogenic variants in SMAD4: A nationwide cross-sectional study

Author

Jelsig, Anne Marie, additional, Qvist, Niels, additional, Bertelsen, Birgitte, additional, Christensen, Lise-Lotte, additional, Grossjohan, Hanne, additional, Lautrup, Charlotte Kvist, additional, Sunde, Lone, additional, Tørring, Pernille Mathiesen, additional, Ljungman, Ken, additional, Christensen, Louise Torp, additional, and Karstensen, John Gásdal, additional

Published
2022
Full Text
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29. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Ottini, Laura, Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., and Ottini, Laura

Abstract

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

30. Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Author

Li, Hongyan, Engel, Christoph, de la Hoya, Miguel, Peterlongo, Paolo, Yannoukakos, Drakoulis, Livraghi, Luca, Radice, Paolo, Thomassen, Mads, Hansen, Thomas V. O., Gerdes, Anne-Marie, Nielsen, Henriette R., Caputo, Sandrine M., Zambelli, Alberto, Borg, Ake, Solano, Angela, Thomas, Abigail, Parsons, Michael T., Antoniou, Antonis C., Leslie, Goska, Yang, Xin, Chenevix-Trench, Georgia, Caldes, Trinidad, Kwong, Ava, Pedersen, Inge Sokilde, Lautrup, Charlotte K., John, Esther M., Terry, Mary Beth, Hopper, John L., Southey, Melissa C., Andrulis, Irene L., Tischkowitz, Marc, Janavicius, Ramunas, Boonen, Susanne E., Kroeldrup, Lone, Varesco, Liliana, Hamann, Ute, Vega, Ana, Palmero, Edenir, I, Garber, Judy, Montagna, Marco, Van Asperen, Christi J., Foretova, Lenka, Greene, Mark H., Selkirk, Tina, Moller, Pal, Toland, Amanda E., Domchek, Susan M., James, Paul A., Thorne, Heather, Eccles, Diana M., Nielsen, Sarah M., Manoukian, Siranoush, Pasini, Barbara, Caligo, Maria A., Lazaro, Conxi, Kirk, Judy, Wappenschmidt, Barbara, Spurdle, Amanda B., Couch, Fergus J., Schmutzler, Rita, Goldgar, David E., Li, Hongyan, Engel, Christoph, de la Hoya, Miguel, Peterlongo, Paolo, Yannoukakos, Drakoulis, Livraghi, Luca, Radice, Paolo, Thomassen, Mads, Hansen, Thomas V. O., Gerdes, Anne-Marie, Nielsen, Henriette R., Caputo, Sandrine M., Zambelli, Alberto, Borg, Ake, Solano, Angela, Thomas, Abigail, Parsons, Michael T., Antoniou, Antonis C., Leslie, Goska, Yang, Xin, Chenevix-Trench, Georgia, Caldes, Trinidad, Kwong, Ava, Pedersen, Inge Sokilde, Lautrup, Charlotte K., John, Esther M., Terry, Mary Beth, Hopper, John L., Southey, Melissa C., Andrulis, Irene L., Tischkowitz, Marc, Janavicius, Ramunas, Boonen, Susanne E., Kroeldrup, Lone, Varesco, Liliana, Hamann, Ute, Vega, Ana, Palmero, Edenir, I, Garber, Judy, Montagna, Marco, Van Asperen, Christi J., Foretova, Lenka, Greene, Mark H., Selkirk, Tina, Moller, Pal, Toland, Amanda E., Domchek, Susan M., James, Paul A., Thorne, Heather, Eccles, Diana M., Nielsen, Sarah M., Manoukian, Siranoush, Pasini, Barbara, Caligo, Maria A., Lazaro, Conxi, Kirk, Judy, Wappenschmidt, Barbara, Spurdle, Amanda B., Couch, Fergus J., Schmutzler, Rita, and Goldgar, David E.

Abstract

Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants. Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2. We analyzed 324 pedigrees with PTC variants in BRCA1 and 214 pedigrees with PTC variants in BRCA2. Cancer risks were estimated using modified segregation analysis. Results: Estimated breast cancer risks were markedly lower for women aged >50 years carrying BRCA1 missense PVs than for the women carrying BRCA1 PTC variants (hazard ratio [HR] = 3.9 [2.4-6.2] for PVs vs 12.8 [5.7-28.7] for PTC variants; P =.01), particularly for missense PVs in the BRCA1 C-terminal domain (HR = 2.8 [1.4-5.6]; P =.005). In case of BRCA2, for women aged >50 years, the HR was 3.9 (2.0-7.2) for those heterozygous for missense PVs compared with 7.0 (3.3-14.7) for those harboring PTC variants. BRCA1 p.[Cys64Arg] and BRCA2 p.[Trp2626Cys] were associated with particularly low risks of breast cancer compared with other PVs. Conclusion: These results have important implications for the counseling of at-risk women who harbor missense PVs in the BRCA1/2 genes. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Published
2022

32. Distinct gastric phenotype in patients with pathogenic variants in SMAD4:A nationwide cross-sectional study

Author

Jelsig, Anne Marie, Qvist, Niels, Bertelsen, Birgitte, Christensen, Lise-Lotte, Grossjohann, Hanne, Lautrup, Charlotte, Sunde, Lone, Toerring, Pernille Mathiesen, Ljungman, Ken, Christensen, Louise Torp, Karstensen, John Gásdal, Jelsig, Anne Marie, Qvist, Niels, Bertelsen, Birgitte, Christensen, Lise-Lotte, Grossjohann, Hanne, Lautrup, Charlotte, Sunde, Lone, Toerring, Pernille Mathiesen, Ljungman, Ken, Christensen, Louise Torp, and Karstensen, John Gásdal

Abstract

Background and study aims In most patients with juvenile polyposis Syndrome, it is possible to detect a pathogenic germline variant in SMAD4 or BMPR1A. It is well known that patients with a pathogenic variant in SMAD4 have a higher risk of gastric polyposis and gastric cancer compared to BMPR1A carriers, but the natural history of gastric involvement is poorly described. We aimed to systematically review endoscopic and histopathological gastric findings in Danish patients with pathogenic variants in SMAD4. Patients and methods This was a retrospective, cross-sectional study including endoscopic and histological gastric findings in all known Danish patients with pathogenic variants in SMAD4. The patients were identified by data from various registries as well as from clinical genetic departments and laboratories. Results We identified 41 patients (2–72 years) with a pathogenic SMAD4 variant. In 31 patients, we were able to retrieve information on upper gastrointestinal endoscopy. Eighty-seven percent had at least one gastric abnormality including erythema (72 %) and edema (72 %). Half of the patients also had vulnerability of the mucosa and 68 % had gastric polyposis. An increasing frequency of abnormalities were observed with increasing age. Gastric cancer was diagnosed in 5 % of the cases and 22 % had a gastrectomy mainly because of massive polyposis. Conclusions This study showed that most patients with pathogenic SMAD4 variants have a distinct phenotype of the gastric mucosa, and with an increasing severity in the elderly patients. These findings provide new insights into the natural history of gastric manifestations in patients with pathogenic SMAD4 variants.

Published
2022

34. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R, Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E, Borg, Åke, Bozsik, Aniko, Brady, Angela F, Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen BM, GEMO Study Collaborators, EMBRACE Collaborators, Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesús, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas VO, Hanson, Helen, Hentschel, Julia, Horvath, Judit, KConFab Investigators, HEBON Investigators, Izatt, Louise, Izquierdo, Angel, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M, Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A, Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernández, Adria, Mai, Phuong L, Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N, Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N, Morrison, Patrick J, Muranen, Taru A, Murray, Alex, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nguyen-Dumont, Tu, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I, Palli, Domenico, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H, Pinto, Pedro, Porteous, Mary E, Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T, Rønlund, Karina, Rump, Andreas, Sánchez de Abajo, Ana María, Shah, Payal D, Sharif, Saba, Side, Lucy E, Singer, Christian F, Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teulé, Alex, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tommasi, Stefania, Toss, Angela, Trainer, Alison H, Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J, Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J, Schmutzler, Rita K, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Antoniou, Antonis C, Ottini, Laura, Consortium of Investigators of Modifiers of BRCA1 and BRCA2, Barnes, Daniel R [0000-0002-3781-7570], Silvestri, Valentina [0000-0003-0712-9379], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Yang, Xin [0000-0003-0037-3790], Adlard, Julian [0000-0002-1693-0435], Agnarsson, Bjarni A [0000-0001-7721-9965], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arnold, Norbert [0000-0003-4523-8808], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Barkardottir, Rosa B [0000-0003-0629-2772], Barrowdale, Daniel [0000-0003-1661-3939], Benitez, Javier [0000-0002-0923-7202], Boonen, Susanne E [0000-0002-7824-2080], Bozsik, Aniko [0000-0001-5410-9173], Brennan, Paul [0000-0003-1128-6254], Brunet, Joan [0000-0003-1945-3512], Bucalo, Agostino [0000-0003-3475-1067], Caligo, Maria A [0000-0003-0589-1829], Campbell, Ian [0000-0002-7773-4155], Cassingham, Hayley [0000-0001-9922-2321], Cini, Giulia [0000-0002-8696-8922], Claes, Kathleen BM [0000-0003-0841-7372], Coppa, Anna [0000-0001-9758-5444], Cortesi, Laura [0000-0001-8950-8561], Darder, Esther [0000-0002-7764-1397], de la Hoya, Miguel [0000-0002-8113-1410], de Putter, Robin [0000-0001-9410-8941], Del Valle, Jesús [0000-0003-3607-7045], Domchek, Susan M [0000-0002-5914-7272], Donaldson, Alan [0000-0001-9193-4172], Eason, Jacqueline [0000-0002-8711-8671], Engel, Christoph [0000-0002-7247-282X], Fostira, Florentia [0000-0003-2751-2332], Frone, Megan [0000-0001-8273-8866], Glendon, Gord [0000-0001-8630-6673], Godwin, Andrew K [0000-0002-3987-9580], Greene, Mark H [0000-0003-1852-9239], Hahnen, Eric [0000-0003-2448-7872], Hanson, Helen [0000-0002-3303-8713], Izatt, Louise [0000-0003-1258-4843], Izquierdo, Angel [0000-0003-2004-3246], James, Paul A [0000-0002-4361-4657], John, Esther M [0000-0003-3259-8003], Kroeldrup, Lone [0000-0003-3623-6536], Kruse, Torben A [0000-0002-2460-6483], Lazaro, Conxi [0000-0002-7198-5906], Lesueur, Fabienne [0000-0001-7404-4549], Matrai, Zoltan [0000-0001-8160-7100], Montagna, Marco [0000-0002-4929-2150], Monteiro, Alvaro N [0000-0002-8448-4801], Morrison, Patrick J [0000-0002-2823-1762], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Neuhausen, Susan L [0000-0001-5053-0390], Nevanlinna, Heli [0000-0002-0916-2976], Nguyen-Dumont, Tu [0000-0002-6217-0182], Niederacher, Dieter [0000-0001-6231-9226], Palli, Domenico [0000-0002-5558-2437], Parsons, Michael T [0000-0003-3242-8477], Perez-Segura, Pedro [0000-0001-5049-7199], Peterlongo, Paolo [0000-0001-6951-6855], Pinto, Pedro [0000-0001-6289-5792], Pottinger, Caroline [0000-0003-4233-882X], Radice, Paolo [0000-0001-6298-4111], Robson, Mark [0000-0002-3109-1692], Rump, Andreas [0000-0001-7116-6364], Sharif, Saba [0000-0002-9564-4890], Steele, Linda [0000-0003-3628-2022], Stoppa-Lyonnet, Dominique [0000-0002-5438-8309], Teixeira, Manuel R [0000-0002-4896-5982], Thull, Darcy L [0000-0001-7999-2804], Tischkowitz, Marc [0000-0002-7880-0628], Toland, Amanda E [0000-0002-0271-1792], Tommasi, Stefania [0000-0002-2157-2978], Toss, Angela [0000-0002-1854-6701], Tripathi, Vishakha [0000-0001-8118-8364], Valentini, Virginia [0000-0003-3393-7185], van Asperen, Christi J [0000-0002-1436-7650], Venturelli, Marta [0000-0003-0658-8004], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Whaite, Anna [0000-0003-4485-0341], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Chenevix-Trench, Georgia [0000-0002-1878-2587], Ottini, Laura [0000-0001-8030-0449], and Apollo - University of Cambridge Repository

Subjects
Aged, 80 and over, BRCA2 Protein, Male, Heterozygote, BRCA1 Protein, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Mutation, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases
Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

35. Additional file 1 of Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Møller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubiński, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Dębniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueñas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.

Abstract

Additional file 1.

Published
2022
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38. Variation in the Risk of Colorectal Cancer for Lynch Syndrome: A retrospective family cohort study

Author

Win, Aung Ko, Dowty, James G., Reece, Jeanette C., Lee, Grant, Templeton, Allyson S., Plazzer, John-Paul, Buchanan, Daniel D., Akagi, Kiwamu, Aksoy, Seçil, Alonso, Angel, Alvarez, Karin, Amor, David J., Ankathil, Ravindran, Aretz, Stefan, Arnold, Julie L., Aronson, Melyssa, Austin, Rachel, Backman, Ann-Sofie, Bajwa–ten Broeke, Sanne W., Barca-Tierno, Verónica, Barwell, Julian, Bernstein, Inge, Berthet, Pascaline, Betz, Beate, Bignon, Yves-Jean, Boisjoli, Talya, Bonadona, Valérie, Briollais, Laurent, Brunet, Joan, Bucksch, Karolin, Buecher, Bruno, Buettner, Reinhard, Burn, John, Caldés, Trinidad, Capella, Gabriel, Caron, Olivier, Casey, Graham, Chew, Min H., Choi, Yun-hee, Church, James, Clendenning, Mark, Colas, Chrystelle, Cops, Elisa J., Coupier, Isabelle, Cruz-Correa, Marcia, de la Chapelle, Albert, de Wind, Niels, Dębniak, Tadeusz, Della Valle, Adriana, Delnatte, Capuccine, Dhooge, Marion, Dominguez-Valentin, Mev, Drouet, Youenn, Duijkers, Floor A., Engel, Christoph, Esperon, Patricia, Evans, D. Gareth, de Vargas, Aída Falcón, Figueiredo, Jane C, Foulkes, William, Fourme, Emmanuelle, Frebourg, Thierry, Gallinger, Steven, Garre, Pilar, Genuardi, Maurizio, Gerdes, Anne-Marie, Gima, Lauren M., Giraud, Sophie, Goodwin, Annabel, Görgens, Heike, Green, Kate, Guillem, Jose, Guillén-Ponce, Carmen, Guimbaud, Roselyne, Guindalini, Rodrigo S. C., Half, Elizabeth E., Hall, Michael J, Hampel, Heather, Hansen, Thomas V. O., Heinimann, Karl, Hes, Frederik J., Hill, James, Ho, Judy W.C., Holinski-Feder, Elke, Hoogerbrugge, Nicoline, Hüneburg, Robert, Huntley, Vanessa, James, Paul A., Jensen, Uffe B, John, Thomas, Juhari, Wan K.W., Kalady, Matthew, Kastrinos, Fay, Kloor, Matthias, Kohonen-Corish, Maija RJ, Krogh, Lotte N., Kupfer, Sonia S., Ladabaum, Uri, Lagerstedt-Robinson, Kristina, Lalloo, Fiona, Lasset, Christine, Latchford, Andrew, Laurent-Puig, Pierre, Lautrup, Charlotte K., Leggett, Barbara A., Lejeune, Sophie, LeMarchand, Loic, Ligtenberg, Marjolijn, Lindor, Noralane, Loeffler, Markus, Longy, Michel, Lopez, Francisco, Lowery, Jan, Lubiński, Jan, Lucassen, Anneke M, Lynch, Patrick M., Malińska, Karolina, Matsubara, Nagahide, Mecklin, Jukka-Pekka, Møller, Pål, Monahan, Kevin, Morrison, Patrick J., Nattermann, Jacob, Navarro, Matilde, Neffa, Florencia, Neklason, Deborah, Newcomb, Polly A., Ngeow, Joanne, Nichols, Cassandra, Nielsen, Maartje, Nixon, Dawn M., Nogues, Catherine, Okkels, Henrik, Olschwang, Sylviane, Pachter, Nicholas, Pai, Rish K., Palmero, Edenir I., Pande, Mala, Parry, Susan, Patel, Swati G., Pearlman, Rachel, Perne, Claudia, Pineda, Marta, Poplawski, Nicola K, Pylvänäinen, Kirsi, Qiu, Jay, Rahner, Nils, Ramesar, Raj, Rasmussen, Lene J., Redler, Silke, Reis, Rui M., Ricciardiello, Luigi, Rogoża-Janiszewska, Emilia, Rosty, Christophe, Samadder, N. Jewel, Sampson, Julian R., Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Schuster, Helène, Scott, Rodney, Senter, Leigha, Seppälä, Toni T, Shtoyerman, Rakefet, Sijmons, Rolf H., Snyder, Carrie, Solomon, Ilana B., Soto, Jose Luis, Southey, Melissa C., Spigelman, Allan, Spirandelli, Florencia, Spurdle, Amanda B., Steinke-Lange, Verena, Stoffel, Elena M., Strassburg, Christian P., Sunde, Lone, Susman, Rachel, Syngal, Sapna, Tanakaya, Kohji, Tezcan, Gülçin, Therkildsen, Christina, Thibodeau, Steve, Tomita, Naohiro, Tucker, Katherine M., Tunca, Berrin, Turchetti, Daniela, Uhrhammer, Nancy, Utsunomiya, Joji, Vaccaro, Carlos, van Duijnhoven, Fränzel J.B., van Wanzeele, Meghan J., Vangala, Deepak B., Vasen, Hans F.A., von Knebel Doeberitz, Magnus, von Salomé, Jenny, Wadt, Karin A. W., Ward, Robyn L., Weitz, Jürgen, Weitzel, Jeffrey N., Williams, Heinric, Winship, Ingrid, Wise, Paul E., Wods, Julie, Woods, Michael O., Yamaguchi, Tatsuro, Zachariae, Silke, Zahary, Mohd N., Hopper, John L., Haile, Robert W., Macrae, Finlay A., Möslein, Gabriela, and Jenkins, Mark A.

Subjects
Article
Abstract

BACKGROUND: Current clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the average age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate how much penetrance varies between carriers of pathogenic variants in the same gene by sex and continent of residence of the carrier. METHODS: We studied 79,809 relatives from 5,255 families, of at least three relatives, in which at least one was a confirmed carrier of a pathogenic or likely pathogenic variant in a mismatch repair gene (1,829 MLH1, 2,179 MSH2, 798 MSH6, 449 PMS2), recruited in 15 countries from North America, Europe and Australasia by the collaborative centres of the International Mismatch Repair Consortium. We used modified segregation analysis conditioned on ascertainment to estimate the average penetrance and modelled unmeasured polygenic factors to estimate the variation in penetrance of colorectal cancer. The existence of familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested using a Wald p-value for the null hypothesis that the polygenic standard deviation is zero. FINDINGS: There was strong evidence of the existence of familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was more prominent for MLH1 and MSH2 variant carriers; depending on gene, sex, and continent, with 7–56% of carriers having a risk of colorectal cancer to age 80 of less than 20%, and 9–44% having a risk of more than 80%, while only 10–19% had a risk of 40–60%. INTERPRETATION: Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessment for precision prevention and early detection of colorectal cancer for Lynch syndrome.

Published
2021

40. Nye arvelige polyposesyndromer som differentialdiagnose hos patienten med tarmpolypper

Author

Jelsig, Anne Marie, Jespersen, Niels, Karstensen, John Gásdal, Ketabi, Zohreh, Rønlund, Karina, Sunde, Lone, Thorlacius-Ussing, Ole, Wadt, Karin, Qvist, Niels, Lautrup, Charlotte Kvist, Jelsig, Anne Marie, Jespersen, Niels, Karstensen, John Gásdal, Ketabi, Zohreh, Rønlund, Karina, Sunde, Lone, Thorlacius-Ussing, Ole, Wadt, Karin, Qvist, Niels, and Lautrup, Charlotte Kvist

Abstract

Hereditary polyposis syndromes (HPS) are a group of rare, inherited syndromes characterised by the presence of histopathological specific or numerous intestinal polyps and a high risk of intestinal and extraintestinal cancer. During the last decade, several new HPS have been discovered, as it is possible to detect pathogenic germline variants in genes not previously known to be associated with polyposis. This review summarises the current knowledge on the syndromes and discusses genetic testing as part of the diagnostic pipeline when suspecting a polyposis syndrome.

Published
2021

42. 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

43. Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high frequency of cancer prone syndromes

Author

Byrjalsen, Anna, Hansen, Thomas V.O., Stoltze, Ulrik K., Mehrjouy, Mana M., Barnkob, Nanna Moeller, Hjalgrim, Lisa L., Mathiasen, René, Lautrup, Charlotte K., Gregersen, Pernille A., Hasle, Henrik, Wehner, Peder S., Tuckuviene, Ruta, Sackett, Peter Wad, Laspiur, Adrian O., Rossing, Maria, Marvig, Rasmus L., Tommerup, Niels, Olsen, Tina Elisabeth, Scheie, David, Gupta, Ramneek, Gerdes, Anne-Marie, Schmiegelow, Kjeld, Wadt, Karin, Byrjalsen, Anna, Hansen, Thomas V.O., Stoltze, Ulrik K., Mehrjouy, Mana M., Barnkob, Nanna Moeller, Hjalgrim, Lisa L., Mathiasen, René, Lautrup, Charlotte K., Gregersen, Pernille A., Hasle, Henrik, Wehner, Peder S., Tuckuviene, Ruta, Sackett, Peter Wad, Laspiur, Adrian O., Rossing, Maria, Marvig, Rasmus L., Tommerup, Niels, Olsen, Tina Elisabeth, Scheie, David, Gupta, Ramneek, Gerdes, Anne-Marie, Schmiegelow, Kjeld, and Wadt, Karin

Abstract

Historically, cancer predisposition syndromes (CPSs) were rarely established for children with cancer. This nationwide, population-based study investigated how frequently children with cancer had or were likely to have a CPS. Children (0-17 years) in Denmark with newly diagnosed cancer were invited to participate in whole-genome sequencing of germline DNA. Suspicion of CPS was assessed according to Jongmans'/McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) criteria and familial cancer diagnoses were verified using population-based registries. 198 of 235 (84.3%) eligible patients participated, of whom 94/198 (47.5%) carried pathogenic variants (PVs) in a CPS gene or had clinical features indicating CPS. Twenty-nine of 198 (14.6%) patients harbored a CPS, of whom 21/198 (10.6%) harbored a childhood-onset and 9/198 (4.5%) an adult-onset CPS. In addition, 23/198 (11.6%) patients carried a PV associated with biallelic CPS. Seven of the 54 (12.9%) patients carried two or more variants in different CPS genes. Seventy of 198 (35.4%) patients fulfilled the Jongmans' and/or MIPOGG criteria indicating an underlying CPS, including two of the 9 (22.2%) patients with an adult-onset CPS versus 18 of the 21 (85.7%) patients with a childhood-onset CPS (p = 0.0022), eight of the additional 23 (34.8%) patients with a heterozygous PV associated with biallelic CPS, and 42 patients without PVs. Children with a central nervous system (CNS) tumor had family members with CNS tumors more frequently than patients with other cancers (11/44, p = 0.04), but 42 of 44 (95.5%) cases did not have a PV in a CPS gene. These results demonstrate the value of systematically screening pediatric cancer patients for CPSs and indicate that a higher proportion of childhood cancers may be linked to predisposing germline variants than previously supposed.

Published
2020

44. 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

45. Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high incidence of cancer prone syndromes

Author

Byrjalsen, Anna, primary, Hansen, Thomas V. O., additional, Stoltze, Ulrik K., additional, Mehrjouy, Mana M., additional, Barnkob, Nanna Moeller, additional, Hjalgrim, Lisa L., additional, Mathiasen, René, additional, Lautrup, Charlotte K., additional, Gregersen, Pernille A., additional, Hasle, Henrik, additional, Wehner, Peder S., additional, Tuckuviene, Ruta, additional, Sackett, Peter Wad, additional, Laspiur, Adrian O., additional, Rossing, Maria, additional, Marvig, Rasmus L., additional, Tommerup, Niels, additional, Olsen, Tina Elisabeth, additional, Scheie, David, additional, Gupta, Ramneek, additional, Gerdes, Anne–Marie, additional, Schmiegelow, Kjeld, additional, and Wadt, Karin, additional

Published
2020
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46. Delineation of musculocontractural Ehlers–Danlos Syndrome caused by dermatan sulfate epimerase deficiency

Author

Lautrup, Charlotte K., primary, Teik, Keng W., additional, Unzaki, Ai, additional, Mizumoto, Shuji, additional, Syx, Delfien, additional, Sin, Heng H., additional, Nielsen, Irene K., additional, Markholt, Sara, additional, Yamada, Shuhei, additional, Malfait, Fransiska, additional, Matsumoto, Naomichi, additional, Miyake, Noriko, additional, and Kosho, Tomoki, additional

Published
2020
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47. 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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50. Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up

Author

Baliakas, Panagiotis, Tesi, Bianca, Wartiovaara-Kautto, Ulla, Stray-Pedersen, Asbjørg, Friis, Lone Smidstrup, Dybedal, Ingunn, Hovland, Randi, Jahnukainen, Kirsi, Raaschou-Jensen, Klas, Ljungman, Per, Rustad, Cecilie F., Lautrup, Charlotte K., Kilpivaara, Outi, Kittang, Astrid Olsnes, Grønbæk, Kirsten, Cammenga, Jörg, Hellström-Lindberg, Eva, Andersen, Mette K., Baliakas, Panagiotis, Tesi, Bianca, Wartiovaara-Kautto, Ulla, Stray-Pedersen, Asbjørg, Friis, Lone Smidstrup, Dybedal, Ingunn, Hovland, Randi, Jahnukainen, Kirsi, Raaschou-Jensen, Klas, Ljungman, Per, Rustad, Cecilie F., Lautrup, Charlotte K., Kilpivaara, Outi, Kittang, Astrid Olsnes, Grønbæk, Kirsten, Cammenga, Jörg, Hellström-Lindberg, Eva, and Andersen, Mette K.

Published
2019
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