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1. 1701P Consensus molecular subtypes in late-stage colorectal cancer

Author: Bjerrum, A., primary, Stannius, T.O., additional, Belcaid, L., additional, Rohrberg, K.S., additional, Spanggaard, I., additional, Hoejgaard, M., additional, NIelsen, F.C., additional, Bagger, F.O., additional, and Qvortrup, C., additional
Published: 2022
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2. 55P Potential benefits of extensive genomic analysis in patients with KRAS mutated solid tumors: Concurrent alterations and potential targets

Author: Jacobsen, I.C., primary, Spanggaard, I., additional, Hoejgaard, M., additional, Belcaid, L., additional, Qvortrup, C., additional, Yde, C.W., additional, Schmidt, A.Y., additional, Nielsen, F.C., additional, Willemoe, G.L., additional, Dam, M.S., additional, Lassen, U., additional, and Rohrberg, K.S., additional
Published: 2022
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3. Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

Author: Qian, F., Wang, S.F., Mitchell, J., McGuffog, L., Barrowdale, D., Leslie, G., Oosterwijk, J.C., Chung, W.K., Evans, D.G., Engel, C., Kast, K., Aalfs, C.M., Adank, M.A., Adlard, J., Agnarsson, B.A., Aittomaki, K., Alducci, E., Andrulis, I.L., Arun, B.K., Ausems, M.G.E.M., Azzollini, J., Barouk-Simonet, E., Barwell, J., Belotti, M., Benitez, J., Berger, A., Borg, A., Bradbury, A.R., Brunet, J., Buys, S.S., Caldes, T., Caligo, M.A., Campbell, I., Caputo, S.M., Chiquette, J., Claes, K.B.M., Collee, J.M., Couch, F.J., Coupier, I., Daly, M.B., Davidson, R., Diez, O., Domchek, S.M., Donaldson, A., Dorfling, C.M., Eeles, R., Feliubadalo, L., Foretova, L., Fowler, J., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Garcia-Barberan, V., Glendon, G., Godwin, A.K., Garcia, E.B.G., Gronwald, J., Hahnen, E., Hamann, U., Henderson, A., Hendricks, C.B., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Izquierdo, A., Jakubowska, A., Kaczmarek, K., Kang, E., Karlan, B.Y., Kets, C.M., Kim, S.W., Kim, Z., Kwong, A., Laitman, Y., Lasset, C., Lee, M.H., Lee, J.W., Lee, J., Lester, J., Lesueur, F., Loud, J.T., Lubinski, J., Mebirouk, N., Meijers-Heijboer, H.E.J., Meindl, A., Miller, A., Montagna, M., Mooij, T.M., Morrison, P.J., Mouret-Fourme, E., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Niederacher, D., Nielsen, F.C., Nussbaum, R.L., Offit, K., Olah, E., Ong, K.R., Ottini, L., Park, S.K., Peterlongo, P., Pfeiler, G., Phelan, C.M., Poppe, B., Pradhan, N., Radice, P., Ramus, S.J., Rantala, J., Robson, M., Rodriguez, G.C., Schmutzler, R.K., Selkirk, C.G.H., Shah, P.D., Simard, J., Singer, C.F., Sokolowska, J., Stoppa-Lyonnet, D., Sutter, C., Tan, Y.Y., Teixeira, M.R., Teo, S.H., Terry, M.B., Thomassen, M., Tischkowitz, M., Toland, A.E., Tucker, K.M., Tung, N., Asperen, C.J. van, Engelen, K. van, Rensburg, E.J. van, Wang-Gohrke, S., Wappenschmidt, B., Weitzel, J.N., Yannoukakos, D., Greene, M.H., Rookus, M.A., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., Goldgar, D.E., Olopade, O.I., Rebbeck, T.R., Huo, D.Z., GEMO Study Collaborators, HEBON, EMBRACE, Clinical Genetics, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Leslie, Goska [0000-0001-5756-6222], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Human Genetics, ARD - Amsterdam Reproduction and Development, Epidemiology and Data Science, Human genetics, CCA - Cancer biology and immunology, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)
Subjects: Oncology, Cancer Research, LOCI, Disease, DISEASE, Body Mass Index, breast cancer risk, 0302 clinical medicine, Risk Factors, GENETIC-VARIANTS, EPIDEMIOLOGY, skin and connective tissue diseases, 2. Zero hunger, BRCA1 Protein, Articles, Prognosis, INSULIN, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], FAMILY, 030220 oncology & carcinogenesis, OBESITY, BIOLOGICAL PATHWAYS, Female, Risk assessment, Adult, medicine.medical_specialty, Breast Neoplasms, Polymorphism, Single Nucleotide, EMBRACE, GEMO Study Collaborators, BMI, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, BRCA1/2, Internal medicine, Mendelian randomization, medicine, Journal Article, Humans, Genetic Predisposition to Disease, HEBON, BRCA2 Protein, IDENTIFICATION, Proportional hazards model, business.industry, Mendelian Randomization Analysis, medicine.disease, Obesity, Confidence interval, Body Height, Mutation, WEIGHT, business, Body mass index
Abstract: Contains fulltext : 206539.pdf (Publisher’s version ) (Closed access) BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.
Published: 2019

4. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), Antoniou, A.C. (Antonis C.), Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), and Antoniou, A.C. (Antonis C.)
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
Published: 2021
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5. Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers (Nature Communications, (2021), 12, 1, (1078), 10.1038/s41467-020-20496-3).

Author: Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., and Antoniou A.C.
Abstract: The original version of this Article contained an error in the spelling of the author Heiko Becher, which was incorrectly given as Heko Becher. This has now been corrected in both the PDF and HTML versions of the Article.Copyright © 2021, The Author(s).
Published: 2021

6. Erratum: Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers (Nature communications (2021) 12 1 (1078)).

Author: Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Adank M.A., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Collee J.M., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., Dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Adank M.A., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Collee J.M., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., Dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Milne R.L., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Radice P., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., and Antoniou A.C.
Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.
Published: 2021

7. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.

Author: Gesta P., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Niederacher D., Nielsen F.C., Nikitina-Zake L., Nogues C., Olah E., Olopade O.I., Ong K.-R., O'Shaughnessy-Kirwan A., Osorio A., Ott C.-E., Papi L., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Peterlongo P., Pfeiler G., Phillips K.-A., Prajzendanc K., Pujana M.A., Radice P., Ramser J., Ramus S.J., Rantala J., Rennert G., Risch H.A., Robson M., Ronlund K., Salani R., Schuster H., Senter L., Shah P.D., Sharma P., Side L.E., Singer C.F., Slavin T.P., Soucy P., Southey M.C., Spurdle A.B., Steinemann D., Steinsnyder Z., Stoppa-Lyonnet D., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thull D.L., Tischkowitz M., Tognazzo S., Toland A.E., Trainer A.H., Tung N., van Engelen K., van Rensburg E.J., Vega A., Vierstraete J., Wagner G., Walker L., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Yadav S., Yang X., Yannoukakos D., Zimbalatti D., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Antoniou A.C., GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Barnes D.R., Rookus M.A., McGuffog L., Leslie G., Mooij T.M., Dennis J., Mavaddat N., Aittomaki K., Andrulis I.L., Arnold N., Arun B.K., Azzollini J., Balmana J., Barkardottir R.B., Benitez J., Bialkowska K., Blanco A.M., Blok M.J., Bonanni B., Boonen S.E., Borg A., Bozsik A., Bradbury A.R., Brunet J., Buys S.S., Caldes T., Caligo M.A., Campbell I., Christensen L.L., Chung W.K., Claes K.B.M., Berthet P., Colas C., Adlard J., Ahmed M., Antoniou A., Barrowdale D., Brennan P., Brewer C., Easton D., Evans D.G., Side L., Collonge-Rame M.-A., Cook J., Daly M.B., Davidson R., de la Hoya M., de Putter R., Delnatte C., Diez O., Ding Y.C., Domchek S.M., Dorfling C.M., Dumont M., Eeles R., Ejlertsen B., Engel C., Faivre L., Foretova L., Fostira F., Friedlander M., Friedman E., Frost D., Ganz P.A., Garber J., Gehrig A., Gerdes A.-M., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gschwantler-Kaulich D., Hahnen E., Hamann U., Hanson H., Hentschel J., Hogervorst F.B.L., Hooning M.J., Horvath J., Hu C., Hulick P.J., Imyanitov E.N., Chenevix-Trench G., Spurdle A., Blok M., Devilee P., Hogervorst F., Hooning M., Mensenkamp A., Meijers-Heijboer H., Rookus M., Engelen K., Andrieu N., Isaacs C., Izatt L., Izquierdo A., Jakubowska A., James P.A., Janavicius R., John E.M., Joseph V., Karlan B.Y., Kast K., Koudijs M., Kruse T.A., Kwong A., Laitman Y., Lasset C., Lazaro C., Lester J., Lesueur F., Liljegren A., Loud J.T., Lubinski J., Mai P.L., Manoukian S., Mari V., Mebirouk N., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller A., Montagna M., Mouret-Fourme E., Mukherjee S., Gesta P., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Niederacher D., Nielsen F.C., Nikitina-Zake L., Nogues C., Olah E., Olopade O.I., Ong K.-R., O'Shaughnessy-Kirwan A., Osorio A., Ott C.-E., Papi L., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Peterlongo P., Pfeiler G., Phillips K.-A., Prajzendanc K., Pujana M.A., Radice P., Ramser J., Ramus S.J., Rantala J., Rennert G., Risch H.A., Robson M., Ronlund K., Salani R., Schuster H., Senter L., Shah P.D., Sharma P., Side L.E., Singer C.F., Slavin T.P., Soucy P., Southey M.C., Spurdle A.B., Steinemann D., Steinsnyder Z., Stoppa-Lyonnet D., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thull D.L., Tischkowitz M., Tognazzo S., Toland A.E., Trainer A.H., Tung N., van Engelen K., van Rensburg E.J., Vega A., Vierstraete J., Wagner G., Walker L., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Yadav S., Yang X., Yannoukakos D., Zimbalatti D., Offit K., Thomassen M., Couch F.J., Schmutzler R.K., Simard J., Easton D.F., Antoniou A.C., GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators, HEBON Investigators, GENEPSO Investigators, Barnes D.R., Rookus M.A., McGuffog L., Leslie G., Mooij T.M., Dennis J., Mavaddat N., Aittomaki K., Andrulis I.L., Arnold N., Arun B.K., Azzollini J., Balmana J., Barkardottir R.B., Benitez J., Bialkowska K., Blanco A.M., Blok M.J., Bonanni B., Boonen S.E., Borg A., Bozsik A., Bradbury A.R., Brunet J., Buys S.S., Caldes T., Caligo M.A., Campbell I., Christensen L.L., Chung W.K., Claes K.B.M., Berthet P., Colas C., Adlard J., Ahmed M., Antoniou A., Barrowdale D., Brennan P., Brewer C., Easton D., Evans D.G., Side L., Collonge-Rame M.-A., Cook J., Daly M.B., Davidson R., de la Hoya M., de Putter R., Delnatte C., Diez O., Ding Y.C., Domchek S.M., Dorfling C.M., Dumont M., Eeles R., Ejlertsen B., Engel C., Faivre L., Foretova L., Fostira F., Friedlander M., Friedman E., Frost D., Ganz P.A., Garber J., Gehrig A., Gerdes A.-M., Giraud S., Glendon G., Godwin A.K., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gschwantler-Kaulich D., Hahnen E., Hamann U., Hanson H., Hentschel J., Hogervorst F.B.L., Hooning M.J., Horvath J., Hu C., Hulick P.J., Imyanitov E.N., Chenevix-Trench G., Spurdle A., Blok M., Devilee P., Hogervorst F., Hooning M., Mensenkamp A., Meijers-Heijboer H., Rookus M., Engelen K., Andrieu N., Isaacs C., Izatt L., Izquierdo A., Jakubowska A., James P.A., Janavicius R., John E.M., Joseph V., Karlan B.Y., Kast K., Koudijs M., Kruse T.A., Kwong A., Laitman Y., Lasset C., Lazaro C., Lester J., Lesueur F., Liljegren A., Loud J.T., Lubinski J., Mai P.L., Manoukian S., Mari V., Mebirouk N., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller A., Montagna M., Mouret-Fourme E., and Mukherjee S.
Abstract: Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Method(s): Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Result(s): The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3x10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7x10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3x10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4x10-12) carriers. The associations in the prospective cohort were similar. Conclusion(s): Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Copyright © 2020, The Author(s).
Published: 2021

8. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Author: Radice P., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R.L., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Robson M., Radice P., Romero A., Rossing M., Saloustros E., Sandler D.P., Santella R., Scheuner M.T., Schmidt M.K., Schmidt G., Scott C., Sharma P., Soucy P., Southey M.C., Spinelli J.J., Steinsnyder Z., Stone J., Stoppa-Lyonnet D., Swerdlow A., Tamimi R.M., Tapper W.J., Taylor J.A., Terry M.B., Teule A., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Trainer A.H., Truong T., Tung N., Vachon C.M., Vega A., Vijai J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wolk A., Yadav S., Yang X.R., Yannoukakos D., Zheng W., Ziogas A., Zorn K.K., Park S.K., Thomassen M., Offit K., Schmutzler R.K., Couch F.J., Simard J., Chenevix-Trench G., Easton D.F., Andrieu N., Antoniou A.C., Coignard J., Lush M., Beesley J., O'Mara T.A., Dennis J., Tyrer J.P., Barnes D.R., McGuffog L., Leslie G., Bolla M.K., Agata S., Ahearn T., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Arnold N., Aronson K.J., Arun B.K., Augustinsson A., Azzollini J., Barrowdale D., Baynes C., Becher H., Bermisheva M., Bernstein L., Bialkowska K., Blomqvist C., Bojesen S.E., Bonanni B., Borg A., Brauch H., Brenner H., Burwinkel B., Buys S.S., Caldes T., Caligo M.A., Campa D., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Chung W.K., Claes K.B.M., Clarke C.L., Bertrand O., Caputo S., Dupre A., Le Mentec M., Belotti M., Birot A.-M., Buecher B., Fourme E., Gauthier-Villars M., Golmard L., Houdayer C., Moncoutier V., de Pauw A., Saule C., Sinilnikova O., Mazoyer S., Damiola F., Barjhoux L., Verny-Pierre C., Leone M., Boutry-Kryza N., Calender A., Giraud S., Caron O., Guillaud-Bataille M., Bressac-de-Paillerets B., Bignon Y.-J., Uhrhammer N., Lasset C., Bonadona V., Berthet P., Vaur D., Castera L., Popovici C., Sobol H., Bourdon V., Noguchi T., Remenieras A., Nogues C., Coupier I., Pujol P., Dumont A., Revillion F., Adenis C., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Sevenet N., Longy M., Toulas C., Guimbaud R., Gladieff L., Feillel V., Leroux D., Dreyfus H., Rebischung C., Peysselon M., Coron F., Faivre L., Baurand A., Jacquot C., Bertolone G., Lizard S., Prieur F., Lebrun M., Kientz C., Ferrer S.F., Mari V., Venat-Bouvet L., Delnatte C., Bezieau S., Mortemousque I., Coulet F., Colas C., Soubrier F., Warcoin M., Sokolowska J., Bronner M., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Gregory H., Miedzybrodzka Z., Morrison P.J., Ong K.-R., Donaldson A., Rogers M.T., Kennedy M.J., Porteous M.E., Brewer C., Davidson R., Izatt L., Brady A., Barwell J., Adlard J., Foo C., Lalloo F., Side L.E., Eason J., Henderson A., Walker L., Eeles R.A., Cook J., Snape K., Eccles D., Murray A., McCann E., Conroy D.M., Czene K., Daly M.B., Devilee P., Diez O., Ding Y.C., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Eliassen A.H., Engel C., Eriksson M., Evans D.G., Fasching P.A., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Barberan V., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Gehrig A., Georgoulias V., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Guenel P., Haeberle L., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hart S.N., He W., Hogervorst F.B.L., Hollestelle A., Hopper J.L., Horcasitas D.J., Hulick P.J., Hunter D.J., Imyanitov E.N., Fox S., Campbell I., Spurdle A., Webb P., de Fazio A., Tassell M., Kirk J., Lindeman G., Price M., Southey M., Milne R.L., Deb S., Bowtell D., van der Hout A.H., van den Ouweland A.M.W., Mensenkamp A.R., van Deurzen C.H.M., Kets C.M., Seynaeve C., van Asperen C.J., Aalfs C.M., Gomez Garcia E.B., van Leeuwen F.E., de Bock G.H., Meijers-Heijboer H.E.J., Obdeijn I.M., Collee J.M., Gille J.J.P., Oosterwijk J.C., Wijnen J.T., van der Kolk L.E., Hooning M.J., Ausems M.G.E.M., Mourits M.J.E., Blok M.J., Rookus M.A., Adank M.A., van der Luijt R.B., van Cronenburg T.C.T.E.F., van der Pol C.C., Russell N.S., Siesling S., Overbeek L., Wijnands R., de Lange J.L., Clarke C., Graham D., Sachchithananthan M., Marsh D., Scott R., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Simpson P., Jager A., Jakubowska A., James P.A., Jensen U.B., John E.M., Jones M.E., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Kosma V.-M., Kraft P., Kurian A.W., Laitman Y., Lambrechts D., Le Marchand L., Lester J., Lesueur F., Lindstrom T., Lopez-Fernandez A., Loud J.T., Luccarini C., Mannermaa A., Manoukian S., Margolin S., Martens J.W.M., Mebirouk N., Meindl A., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nielsen F.C., O'Brien K.M., Olopade O.I., Olson J.E., Olsson H., Osorio A., Ottini L., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peshkin B., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Polley E.C., Poppe B., Presneau N., Pujana M.A., Punie K., Rantala J., Rashid M.U., Rennert G., Rennert H.S., and Robson M.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.Copyright © 2021, The Author(s).
Published: 2021

9. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author: Fachal, L., Aschard, H., Beesley, J., Barnes, D.R., Allen, J., Kar, S., Pooley, K.A., Dennis, J., Michailidou, K., Turman, C., Soucy, P., Lemaçon, A., Lush, M., Tyrer, J.P., Ghoussaini, M., Marjaneh, M.M., Jiang, X., Agata, S., Aittomäki, K., Alonso, M.R., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Aronson, K.J., Arun, B.K., Auber, B., Auer, P.L., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Białkowska, K., Blanco, A.M., Blomqvist, C., Blot, W., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bonanni, B., Borg, A., Bosse, K., Brauch, H., Brenner, H., Briceno, I., Brock, I.W., Brooks-Wilson, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldés, T., Caligo, M.A., Camp, N.J., Campbell, I., Canzian, F., Carroll, J.S., Carter, B.D., Castelao, J.E., Chiquette, J., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Mari, V., Berthet, P., Castera, L., Vaur, D., Lallaoui, H., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Lasset, C., Révillion, F., Vennin, P., Muller, D., Gomes, D.M., Ingster, O., Coupier, I., Pujol, P., Collonge-Rame, M.-A., Mortemousque, I., Bera, O., Rose, M., Baurand, A., Bertolone, G., Faivre, L., Dreyfus, H., Leroux, D., Venat-Bouvet, L., Bézieau, S., Delnatte, C., Chiesa, J., Gilbert-Dussardier, B., Gesta, P., Prieur, F.P., Bronner, M., Sokolowska, J., Coulet, F., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Fert-Ferrer, S., Stoppa-Lyonnet, D., Jiao, Y., Lesueur, F.L., Mebirouk, N., Barouk-Simonet, E., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Toulas, C., Reimineras, A., Sobol, H., Paillerets, B.B.-D., Cabaret, O., Caron, O., Guillaud-Bataille, M., Rouleau, E., Belotti, M., Buecher, B., Caputo, S., Colas, C., Pauw, A.D., Fourme, E., Gauthier-Villars, M., Golmard, L., Moncoutier, V., Saule, C., Donaldson, A., Murray, A., Brady, A., Brewer, C., Pottinger, C., Miller, C., Gallagher, D., Gregory, H., Cook, J., Eason, J., Adlard, J., Barwell, J., Ong, K.-R., Snape, K., Walker, L., Izatt, L., Side, L., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Ahmed, M., Morrison, P.J., Brennan, P., Eeles, R., Davidson, R., Collée, M., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Cybulski, C., Czene, K., Daly, M.B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y.C., Dite, G.S., Domchek, S.M., Dörk, T., dos-Santos-Silva, I., Droit, A., Dubois, S., Dumont, M., Duran, M., Durcan, L., Dwek, M., Eccles, D.M., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Fletcher, O., Floris, G., Flyger, H., Foretova, L., Foulkes, W.D., Friedman, E., Fritschi, L., Frost, D., Gabrielson, M., Gago-Dominguez, M., Gambino, G., Ganz, P.A., Gapstur, S.M., Garber, J., García-Sáenz, J.A., Gaudet, M.M., Georgoulias, V., Giles, G., Glendon, G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Tibiletti, M.G., Greene, M.H., Grip, M., Gronwald, J., Grundy, A., Guénel, P., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, P., Hamann, U., Harrington, P.A., Hartikainen, J.M., Hartman, M., He, W., Healey, C.S., Heemskerk-Gerritsen, B.A.M., Heyworth, J., Hillemanns, P., Hogervorst, F.B.L., Hollestelle, A., Hooning, M., Hopper, J., Howell, A., Huang, G., Hulick, P.J., Imyanitov, E.N., Sexton, A., Christian, A., Trainer, A., Spigelman, A., Fellows, A., Shelling, A., Fazio, A.D., Blackburn, A., Crook, A., Meiser, B., Patterson, B., Clarke, C., Saunders, C., Hunt, C., Scott, C., Amor, D., Marsh, D., Edkins, E., Salisbury, E., Haan, E., Neidermayr, E., Macrea, F., Farshid, G., Lindeman, G., Chenevix-Trench, G., Mann, G., Gill, G., Thorne, H., Hickie, I., Winship, I., Flanagan, J., Kollias, J., Visvader, J., Stone, J., Taylor, J., Burke, J., Saunus, J., Forbes, J., Kirk, J., French, J., Tucker, K., Wu, K., Phillips, K., Lipton, L., Andrews, L., Lobb, L., Kentwell, M., Spurdle, M., Cummings, M., Gleeson, M., Harris, M., Jenkins, M., Young, M.A., Delatycki, M., Wallis, M., Burgess, M., Price, M., Brown, M., Southey, M., Bogwitz, M., Field, M., Friedlander, M., Gattas, M., Saleh, M., Hayward, N., Pachter, N., Cohen, P., Duijf, P., James, P., Simpson, P., Fong, P., Butow, P., Williams, R., Kefford, R., Scott, R., Milne, R.L., Balleine, R., Dawson, S.–J., Lok, S., O’Connell, S., Greening, S., Nightingale, S., Edwards, S., Fox, S., McLachlan, S.-A., Lakhani, S., Antill, Y., Aalfs, C., Meijers-Heijboer, H., van Engelen, K., Gille, H., Boere, I., van Deurzen, C., Obdeijn, I.-M., van den Ouweland, A., Seynaeve, C., Siesling, S., Verloop, J., van Asperen, C.J., van Cronenburg, T., Blok, R., de Boer, M., Garcia, E.G., Adank, M., Hogervorst, F., Jenner, D., van Leeuwen, F., Rookus, M., Russell, N., Schmidt, M., van den Belt-Dusebout, S., Kets, C., Mensenkamp, A., de Bock, T., van der Hout, A., Mourits, M., Oosterwijk, J., Ausems, M., Koudijs, M., Baxter, R., Yip, D., Carpenter, J., Davis, A., Pathmanathan, N., Graham, D., Sachchithananthan, M., Isaacs, C., Iwasaki, M., Jager, A., Jakimovska, M., Jakubowska, A., James, P.A., Janavicius, R., Jankowitz, R.C., John, E.M., Johnson, N., Jones, M.E., Jukkola-Vuorinen, A., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Karlan, B.Y., Keeman, R., Kerin, M.J., Khusnutdinova, E., Kiiski, J.I., Kitahara, C.M., Ko, Y.-D., Konstantopoulou, I., Kosma, V.-M., Koutros, S., Kubelka-Sabit, K., Kwong, A., Kyriacou, K., Laitman, Y., Lambrechts, D., Lee, E., Leslie, G., Lester, J., Lesueur, F., Lindblom, A., Lo, W.-Y., Long, J., Lophatananon, A., Loud, J.T., Lubiński, J., MacInnis, R.J., Maishman, T., Makalic, E., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matsuo, K., Maurer, T., Mavroudis, D., Mayes, R., McGuffog, L., McLean, C., Meindl, A., Miller, A., Miller, N., Montagna, M., Moreno, F., Muir, K., Mulligan, A.M., Muñoz-Garzon, V.M., Muranen, T.A., Narod, S.A., Nassir, R., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Nielsen, F.C., Nikitina-Zake, L., Norman, A., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Osorio, A., Pankratz, V.S., Papp, J., Park, S.K., Park-Simon, T.-W., Parsons, M.T., Paul, J., Pedersen, I.S., Peissel, B., Peshkin, B., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Presneau, N., Prokofyeva, D., Pujana, M.A., Pylkäs, K., Radice, P., Ramus, S.J., Rantala, J., Rau-Murthy, R., Rennert, G., Risch, H.A., Robson, M., Romero, A., Rossing, M., Saloustros, E., Sánchez-Herrero, E., Sandler, D.P., Santamariña, M., Sawyer, E.J., Scheuner, M.T., Schmidt, D.F., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schöttker, B., Schürmann, P., Scott, R.J., Senter, L., Seynaeve, C.M., Shah, M., Sharma, P., Shen, C.-Y., Shu, X.-O., Singer, C.F., Slavin, T.P., Smichkoska, S., Southey, M.C., Spinelli, J.J., Spurdle, A.B., Sutter, C., Swerdlow, A.J., Tamimi, R.M., Tan, Y.Y., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Tengström, M., Teo, S.H., Terry, M.B., Teulé, A., Thomassen, M., Thull, D.L., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Torres-Mejía, G., Troester, M.A., Truong, T., Tung, N., Tzardi, M., Ulmer, H.-U., Vachon, C.M., van der Kolk, L.E., van Rensburg, E.J., Vega, A., Viel, A., Vijai, J., Vogel, M.J., Wang, Q., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wendt, C., Wildiers, H., Winqvist, R., Wolk, A., Wu, A.H., Yannoukakos, D., Zhang, Y., Zheng, W., Hunter, D., Pharoah, P.D.P., Chang-Claude, J., García-Closas, M., Schmidt, M.K., Kristensen, V.N., French, J.D., Edwards, S.L., Antoniou, A.C., Simard, J., Easton, D.F., Kraft, P., Dunning, A.M., Collaborators, GEMO Study, Collaborators, EMBRACE, Investigators, KConFab, Investigators, HEBON, Investigators, ABCTB, Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Duijf, Pascal, Dunning, Alison M, GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), European Commission, Government of Canada, Canadian Institutes of Health Research, National Institutes of Health (US), Cancer Research UK, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, University of Cambridge [UK] (CAM), NSCAD, University of Cyprus [Nicosia], Harvard T.H. Chan School of Public Health, This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation), the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492), and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note., We thank all of the individuals who took part in these studies, as well as all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out, European Project: 656144,H2020,H2020-MSCA-IF-2014,RADIOGENFF(2016), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), Clinical Genetics, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia] (UCY), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Targeted Gynaecologic Oncology (TARGON), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Aschard, Hugues [0000-0002-7554-6783], Barnes, Daniel R [0000-0002-3781-7570], Dennis, Joe [0000-0003-4591-1214], Michailidou, Kyriaki [0000-0001-7065-1237], Lemaçon, Audrey [0000-0002-1817-7029], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Campbell, Ian [0000-0002-7773-4155], Carroll, Jason S [0000-0003-3643-0080], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Fletcher, Olivia [0000-0001-9387-7116], Floris, Giuseppe [0000-0003-2391-5425], Foulkes, William D [0000-0001-7427-4651], García-Sáenz, José A [0000-0001-6880-0301], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Matsuo, Keitaro [0000-0003-1761-6314], McLean, Catriona [0000-0002-0302-5727], Miller, Austin [0000-0001-9739-8462], Muir, Kenneth [0000-0001-6429-988X], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Pankratz, V Shane [0000-0002-3742-040X], Parsons, Michael T [0000-0003-3242-8477], Paul, James [0000-0001-7367-5816], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Scott, Rodney J [0000-0001-7724-3404], Spurdle, Amanda B [0000-0003-1337-7897], Stone, Jennifer [0000-0001-5077-0124], Sutter, Christian [0000-0003-4051-5888], Tan, Yen Yen [0000-0003-1063-5352], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Pharoah, Paul DP [0000-0001-8494-732X], Schmidt, Marjanka K [0000-0002-2228-429X], Milne, Roger L [0000-0001-5764-7268], Edwards, Stacey L [0000-0001-7428-4139], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Kraft, Peter [0000-0002-4472-8103], Dunning, Alison M [0000-0001-6651-7166], Apollo - University of Cambridge Repository, Academic Medical Center, ARD - Amsterdam Reproduction and Development, Human genetics, CCA - Cancer biology and immunology, Molecular cell biology and Immunology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Doctoral Programme in Clinical Research, Staff Services, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, and Department of Obstetrics and Gynecology
Subjects: CHROMATIN, Linkage disequilibrium, Genome-wide association study, Regulatory Sequences, Nucleic Acid, Genome-wide association studies, Linkage Disequilibrium, Basic medicine, 0302 clinical medicine, Breast cancer, MESH: Risk Factors, Risk Factors, COMPREHENSIVE MOLECULAR PORTRAITS, 11 Medical and Health Sciences, HEBON Investigators, Genetics & Heredity, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], PROTEIN FUNCTION, Tumor, breast tumor, MESH: Polymorphism, Single Nucleotide, 1184 Genetics, developmental biology, physiology, MESH: Genetic Predisposition to Disease, apoptosis, Chromosome Mapping, Single Nucleotide, 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: Biomarkers, Tumor, Biomarkers, Tumor/genetics, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, SUSCEPTIBILITY LOCI, MESH: Bayes Theorem, Quantitative Trait Loci, ABCTB Investigators, INTEGRATIVE ANALYSIS, Breast Neoplasms, Computational biology, Biology, Quantitative trait locus, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, Article, ENHANCER, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, REVEALS, Genetics, Biomarkers, Tumor, MESH: Regulatory Sequences, Nucleic Acid, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, FUNCTIONAL VARIANTS, EMBRACE Collaborators, Gene, 030304 developmental biology, Genetic association, Bayes Theorem, Genome-Wide Association Study, MESH: Humans, Science & Technology, Nucleic Acid, gene mapping, 06 Biological Sciences, MESH: Quantitative Trait Loci, DNA binding site, ESTROGEN-RECEPTOR, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Clinical medicine, Expression quantitative trait loci, MESH: Genome-Wide Association Study, Human genome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, KConFab Investigators, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Chromosome Mapping, Chromosome Mapping/methods, Regulatory Sequences, MESH: Female, Biomarkers, 030217 neurology & neurosurgery, MESH: Breast Neoplasms, Developmental Biology
Abstract: Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes., This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation); the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE; part of the GAME-ON initiative).
Published: 2020

10. The spectrum of fancm protein truncating variants in European breast cancer cases.

Author: Torngren T., Teixeira M., Toss A., Urioste M., Vega A., Vlckova Z., Yannoukakos D., Zampiga V., Kleibl Z., Radice P., Nevanlinna H., Ehrencrona H., Janavicius R., Peterlongo P., Figlioli G., Kvist A., Tham E., Soukupova J., Kleiblova P., Muranen T.A., Andrieu N., Azzollini J., Balmana J., Barroso A., Benitez J., Bertelsen B., Blanco A., Bonanni B., Borg A., Brunet J., Calistri D., Calvello M., Chvojka S., Cortesi L., Darder E., Del Valle J., Diez O., Eon-Marchais S., Fostira F., Gensini F., Houdayer C., Janatova M., Kiiski J.I., Konstantopoulou I., Kubelka-Sabit K., Lazaro C., Lesueur F., Manoukian S., Marcinkute R., Mickys U., Moncoutier V., Myszka A., Nguyen-Dumont T., Nielsen F.C., Norvilas R., Olah E., Osorio A., Papi L., Peissel B., Peixoto A., Plaseska-Karanfilska D., Pocza T., Rossing M., Rudaitis V., Santamarina M., Santos C., Smichkoska S., Southey M.C., Stoppa-Lyonnet D., Torngren T., Teixeira M., Toss A., Urioste M., Vega A., Vlckova Z., Yannoukakos D., Zampiga V., Kleibl Z., Radice P., Nevanlinna H., Ehrencrona H., Janavicius R., Peterlongo P., Figlioli G., Kvist A., Tham E., Soukupova J., Kleiblova P., Muranen T.A., Andrieu N., Azzollini J., Balmana J., Barroso A., Benitez J., Bertelsen B., Blanco A., Bonanni B., Borg A., Brunet J., Calistri D., Calvello M., Chvojka S., Cortesi L., Darder E., Del Valle J., Diez O., Eon-Marchais S., Fostira F., Gensini F., Houdayer C., Janatova M., Kiiski J.I., Konstantopoulou I., Kubelka-Sabit K., Lazaro C., Lesueur F., Manoukian S., Marcinkute R., Mickys U., Moncoutier V., Myszka A., Nguyen-Dumont T., Nielsen F.C., Norvilas R., Olah E., Osorio A., Papi L., Peissel B., Peixoto A., Plaseska-Karanfilska D., Pocza T., Rossing M., Rudaitis V., Santamarina M., Santos C., Smichkoska S., Southey M.C., and Stoppa-Lyonnet D.
Abstract: Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Published: 2020

11. Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness.

Author: Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., Scarpitta R., Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., and Scarpitta 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 30 region of BRCA2 (c.7914) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR 1/4 1.78; 95% confidence interval (CI), 1.25-2.52; P 1/4 0.001], as well as elevated risk of Gleason 8 prostate cancer (HR 1/4 3.11; 95% CI, 1.63-5.95; P 1/4 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR 1/4 2.83; 95% CI, 1.71-4.68; P 1/4 0.00004) and elevated risk of Gleason 8 prostate cancer (HR 1/4 4.95; 95% CI, 2.12-11.54; P 1/4 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.Copyright © 2020 American Association for Cancer Research.
Published: 2020

12. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Author: Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., Schmutzler R.K., Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., and Schmutzler R.K.
Abstract: Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2020

13. Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Author: Eriksson M., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Plaseska-Karanfilska D., Poppe B., Pradhan N., Prajzendanc K., Presneau N., Punie K., Pylkas K., Radice P., Rantala J., Rashid M.U., Rennert G., Risch H.A., Robson M., Romero A., Saloustros E., Sandler D.P., Santos C., Sawyer E.J., Schmidt M.K., Schmidt D.F., Schmutzler R.K., Schoemaker M.J., Scott R.J., Sharma P., Shu X.-O., Simard J., Singer C.F., Skytte A.-B., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Vieiro-Balo P., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Milne R.L., Easton D.F., Chenevix-Trench G., Zheng W., Kraft P., Jiang X., Feng H., Gusev A., Pasaniuc B., Wu L., Long J., Abu-full Z., Aittomaki K., Andrulis I.L., Anton-Culver H., Antoniou A.C., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Bruning T., Burwinkel B., Cai Q., Caldes T., Caligo M.A., Campbell I., Canisius S., Campa D., Carter B.D., Carter J., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., De Leeneer K., Dennis J., Devilee P., Diez O., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Fasching P.A., Fletcher O., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gabrielson M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., Hake C., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Huang G., Hulick P.J., Humphreys K., Imyanitov E.N., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Jung A., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leroux D., Leslie G., Lester J., Lesueur F., Lindor N., Lindstrom S., Lo W.-Y., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Martinez M.E., Matricardi L., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Kapoor P.M., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peixoto A., Eriksson M., Peterlongo P., Peto J., Pharoah P.D.P., Phillips K.-A., Plaseska-Karanfilska D., Poppe B., Pradhan N., Prajzendanc K., Presneau N., Punie K., Pylkas K., Radice P., Rantala J., Rashid M.U., Rennert G., Risch H.A., Robson M., Romero A., Saloustros E., Sandler D.P., Santos C., Sawyer E.J., Schmidt M.K., Schmidt D.F., Schmutzler R.K., Schoemaker M.J., Scott R.J., Sharma P., Shu X.-O., Simard J., Singer C.F., Skytte A.-B., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Vieiro-Balo P., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Milne R.L., Easton D.F., Chenevix-Trench G., Zheng W., Kraft P., Jiang X., Feng H., Gusev A., Pasaniuc B., Wu L., Long J., Abu-full Z., Aittomaki K., Andrulis I.L., Anton-Culver H., Antoniou A.C., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Boeckx B., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Bruning T., Burwinkel B., Cai Q., Caldes T., Caligo M.A., Campbell I., Canisius S., Campa D., Carter B.D., Carter J., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., De Leeneer K., Dennis J., Devilee P., Diez O., Domchek S.M., Dork T., dos-Santos-Silva I., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Fasching P.A., Fletcher O., Flyger H., Fostira F., Friedman E., Fritschi L., Frost D., Gabrielson M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., Hake C., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Huang G., Hulick P.J., Humphreys K., Imyanitov E.N., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Jung A., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leroux D., Leslie G., Lester J., Lesueur F., Lindor N., Lindstrom S., Lo W.-Y., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Martinez M.E., Matricardi L., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Kapoor P.M., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., and Peixoto A.
Abstract: Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Copyright © 2020 The Authors. Genetic Epidemiology published by Wiley Periodicals, Inc.
Published: 2020

14. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Author: Goldgar D.E., Newman W.G., Nielsen F.C., Nikitina-Zake L., Nodora J., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Papi L., Papp J., Park-Simon T.-W., Parsons M.T., Peissel B., Peixoto A., Peshkin B., Peterlongo P., Peto J., Phillips K.-A., Piedmonte M., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Prokofyeva D., Rack B., Radice P., Ramus S.J., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Risch H.A., Romero A., Rookus M.A., Rubner M., Rudiger T., Saloustros E., Sampson S., Sandler D.P., Sawyer E.J., Scheuner M.T., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Senter L., Sharma P., Sherman M.E., Shu X.-O., Singer C.F., Smichkoska S., Soucy P., Southey M.C., Spinelli J.J., Stone J., Stoppa-Lyonnet D., Swerdlow A.J., Szabo C.I., Tamimi R.M., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Thomassen M., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., vanRensburg E.J., Vega A., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wildiers H., Winqvist R., Wolk A., Yang X.R., Yannoukakos D., Zheng W., Zorn K.K., Milne R.L., Kraft P., Simard J., Pharoah P.D.P., Michailidou K., Antoniou A.C., Schmidt M.K., Chenevix-Trench G., Easton D.F., Chatterjee N., Garcia-Closas M., Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O'Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Arun B.K., Auer P.L., Azzollini J., Barrowdale D., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bonanni B., Bondavalli D., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Brucker S.Y., Bruning T., Burwinkel B., Buys S.S., Byers H., Caldes T., Caligo M.A., Calvello M., Campa D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiaens M., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Cornelissen S., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Diez O., Domchek S.M., Dork T., Dwek M., Eccles D.M., Ekici A.B., Evans D.G., Fasching P.A., Figueroa J., Foretova L., Fostira F., Friedman E., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haberle L., Hahnen E., Haiman C.A., Hake C.R., Hall P., Hamann U., Harkness E.F., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Holleczek B., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Howell A., Huebner H., Hulick P.J., Imyanitov E.N., Isaacs C., Izatt L., Jager A., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khan S., Khusnutdinova E., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Koppert L.B., Koutros S., Kristensen V.N., Laenkholm A.-V., Lambrechts D., Larsson S.C., Laurent-Puig P., Lazaro C., Lazarova E., Lejbkowicz F., Leslie G., Lesueur F., Lindblom A., Lissowska J., Lo W.-Y., Loud J.T., Lubinski J., Lukomska A., MacInnis R.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matricardi L., McGuffog L., McLean C., Mebirouk N., Meindl A., Menon U., Miller A., Mingazheva E., Montagna M., Mulligan A.M., Mulot C., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Goldgar D.E., Newman W.G., Nielsen F.C., Nikitina-Zake L., Nodora J., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Papi L., Papp J., Park-Simon T.-W., Parsons M.T., Peissel B., Peixoto A., Peshkin B., Peterlongo P., Peto J., Phillips K.-A., Piedmonte M., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Prokofyeva D., Rack B., Radice P., Ramus S.J., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Risch H.A., Romero A., Rookus M.A., Rubner M., Rudiger T., Saloustros E., Sampson S., Sandler D.P., Sawyer E.J., Scheuner M.T., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Senter L., Sharma P., Sherman M.E., Shu X.-O., Singer C.F., Smichkoska S., Soucy P., Southey M.C., Spinelli J.J., Stone J., Stoppa-Lyonnet D., Swerdlow A.J., Szabo C.I., Tamimi R.M., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Thomassen M., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., vanRensburg E.J., Vega A., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wildiers H., Winqvist R., Wolk A., Yang X.R., Yannoukakos D., Zheng W., Zorn K.K., Milne R.L., Kraft P., Simard J., Pharoah P.D.P., Michailidou K., Antoniou A.C., Schmidt M.K., Chenevix-Trench G., Easton D.F., Chatterjee N., Garcia-Closas M., Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O'Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Arun B.K., Auer P.L., Azzollini J., Barrowdale D., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bonanni B., Bondavalli D., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Brucker S.Y., Bruning T., Burwinkel B., Buys S.S., Byers H., Caldes T., Caligo M.A., Calvello M., Campa D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiaens M., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Cornelissen S., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Diez O., Domchek S.M., Dork T., Dwek M., Eccles D.M., Ekici A.B., Evans D.G., Fasching P.A., Figueroa J., Foretova L., Fostira F., Friedman E., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haberle L., Hahnen E., Haiman C.A., Hake C.R., Hall P., Hamann U., Harkness E.F., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Holleczek B., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Howell A., Huebner H., Hulick P.J., Imyanitov E.N., Isaacs C., Izatt L., Jager A., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khan S., Khusnutdinova E., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Koppert L.B., Koutros S., Kristensen V.N., Laenkholm A.-V., Lambrechts D., Larsson S.C., Laurent-Puig P., Lazaro C., Lazarova E., Lejbkowicz F., Leslie G., Lesueur F., Lindblom A., Lissowska J., Lo W.-Y., Loud J.T., Lubinski J., Lukomska A., MacInnis R.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matricardi L., McGuffog L., McLean C., Mebirouk N., Meindl A., Menon U., Miller A., Mingazheva E., Montagna M., Mulligan A.M., Mulot C., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., and Neven P.
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2020

15. A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

Author: Kolte, A.M., Nielsen, H.S., Moltke, I., Degn, B., Pedersen, B., Sunde, L., Nielsen, F.C., and Christiansen, O.B.
Published: 2011
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16. Incidence and characteristics of HPV-associated oropharyngeal cancer: An 18-year Danish population-based study with 2,169 patients

Author: Zamani, M., primary, Grønhøj, C., additional, Hellelstrup, D., additional, Carlander, A., additional, Agander, T., additional, Kiss, K., additional, Olsen, C., additional, Baandrup, L., additional, Nielsen, F.C., additional, Andersen, E., additional, Friborg, J.T., additional, and Buchwald, C.V., additional
Published: 2020
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17. Survival and characteristics of 772 patients with oropharyngeal cancer and specific human papillomavirus genotypes: A Danish population-based study from 2011-2017

Author: Carlander, A., primary, Zamani, M., additional, Larsen, C.G., additional, Hellelstrup, D., additional, Agander, T., additional, Kiss, K., additional, Olsen, C., additional, Baandrup, L., additional, Nielsen, F.C., additional, Andersen, E., additional, Friborg, J.T., additional, and Buchwald, C.V., additional
Published: 2020
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18. Gene expression profiles of single human mature oocytes in relation to age

Author: Grøndahl, M.L., Yding Andersen, C., Bogstad, J., Nielsen, F.C., Meinertz, H., and Borup, R.
Published: 2010
Full Text: View/download PDF

19. Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Author: Jiang, X., Finucane, H.K., Schumacher, F.R., Schmit, S.L., Tyrer, J.P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K.B., Dennis, J., Conti, D.V., Casey, G., Gaudet, M.M., Huyghe, J.R., Albanes, D., Aldrich, M.C., Andrew, A.S., Andrulis, I.L., Anton-Culver, H., Antoniou, A.C., Antonenkova, N.N., Arnold, S.M., Aronson, K.J., Arun, B.K., Bandera, E.V., Barkardottir, R.B., Barnes, D.R., Batra, J., Beckmann, M.W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S.I., Bickeboller, H., Bien, S.A., Blomqvist, C., Boccia, S., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Brauch, H., Brenner, H., Brenton, J.D., Brook, M.N., Brunet, J., Brunnstrom, H., Buchanan, D.D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M.A., Campbell, I., Campbell, P.T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A.L., Chan, A.T., Chang-Claude, J., Chanock, S.J., Chen, C., Christiani, D.C., Claes, K.B.M., Claessens, F., Clements, J., Collee, J.M., Correa, M.C., Couch, F.J., Cox, A., Cunningham, J.M., Cybulski, C., Czene, K., Daly, M.B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J.L., Dork, T., Duell, E.J., Dunning, A.M., Dwek, M., Eccles, D.M., Edlund, C.K., Edwards, D.R.V., Ellberg, C., Evans, D.G., Fasching, P.A., Ferris, R.L., Liloglou, T., Figueiredo, J.C., Fletcher, O., Fortner, R.T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S.J., Ganz, P.A., Garber, J., Garcia-Saenz, J.A., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Goode, E.L., Goodman, M.T., Goodman, G., Grankvist, K., Greene, M.H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F.C., Hamilton, R.J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y.C., Hopper, J.L., Houlston, R., Hulick, P.J., Hunter, D.J., Huntsman, D.G., Idos, G., Imyanitov, E.N., Ingles, S.A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M.A., Johansson, M., John, E.M., Joshi, A.D., Kaneva, R., Karlan, B.Y., Kelemen, L.E., Kuhl, T., Khaw, K.T., Khusnutdinova, E., Kibel, A.S., Kiemeney, L.A., Kim, J., Kjaer, S.K., Knight, J.A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V.N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M.T., Lazarus, P., N.D. le, Lee, E., Lejbkowicz, F., Lenz, H.J., Leslie, G., Lessel, D., Lester, J., Levine, D.A., Li, L., Li, C.I., Lindblom, A., Lindor, N.M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R.L., MacInnis, R.J., Modugno, F., Montagna, M., Moreno, V., Moysich, K.B., Mucci, L., Muir, K., Mulligan, A.M., Nathanson, K.L., Neal, D.E., Ness, A.R., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Newcomb, L.F., Nielsen, F.C., Nikitina-Zake, L., Nordestgaard, B.G., Nussbaum, R.L., Offit, K., Olah, E., Olama, A.A. al, Olopade, O.I., Olshan, A.F., Olsson, H., Osorio, A., Pandha, H., Park, J.Y., Pashayan, N., Parsons, M.T., Pejovic, T., Penney, K.L., Peters, W.H.M., Phelan, C.M., Phipps, A.I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S.J., Raskin, L., Rennert, G., Rennert, H.S., Rensburg, E.J., Riggan, M.J., Risch, H.A., Risch, A., Roobol, M.J., Rosenstein, B.S., Rossing, M.A., Ruyck, K., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schabath, M.B., Schleutker, J., Schmidt, M.K., Setiawan, V.W., Shen, H.B., Siegel, E.M., Sieh, W., Singer, C.F., Slattery, M.L., Sorensen, K.D., Southey, M.C., Spurdle, A.B., Stanford, J.L., Stevens, V.L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A.J., Tajara, E.H., Tangen, C.M., Tardon, A., Taylor, J.A., Teare, M.D., Teixeira, M.R., Terry, M.B., Terry, K.L., Thibodeau, S.N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A.E., Torres, D., Townsend, P.A., Travis, R.C., Tung, N., and Tworoger
Published: 2019

20. Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Author: Qian, F., Rookus, Matti A., Leslie, G., Risch, H.A., Greene, M.H., Aalfs, C.M., Adank, M.A., Adlard, J., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Andrulis, I.L., Arnold, N., Arun, B.K., Ausems, M., Azzollini, J., Barrowdale, D., Barwell, J., Benitez, J., Bialkowska, K., Bonadona, V., Borde, J., Borg, A., Bradbury, A.R., Brunet, J., Buys, S.S., Caldes, T., Caligo, M.A., Campbell, I., Carter, J., Chiquette, J., Chung, W.K., Claes, K.B.M., Collee, J.M., Collonge-Rame, M.A., Couch, F.J., Daly, M.B., Delnatte, C., Diez, O., Domchek, S.M., Dorfling, C.M., Eason, J., Easton, D.F., Eeles, R., Engel, C., Evans, D.G., Faivre, L., Feliubadalo, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Garcia-Barberan, V., Gehrig, A., Glendon, G., Godwin, A.K., Garcia, E.B., Hamann, U., Hauke, J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., Janavicius, R., John, E.M., Karlan, B.Y., Kets, C.M., Laitman, Y., Lazaro, C., Leroux, D., Lester, J., Lesueur, F., Loud, J.T., Lubinski, J., Lukomska, A., McGuffog, L., Mebirouk, N., Meijers-Heijboer, H.E., Meindl, A., Miller, A., Montagna, M., Mooij, T.M., Mouret-Fourme, E., Nathanson, K.L., Nehoray, B., Neuhausen, S.L., Nevanlinna, H., Nielsen, F.C., Offit, K., Olah, E., Ong, K.R., Oosterwijk, J.C, Ottini, L., Parsons, M.T., Peterlongo, P., Pfeiler, G., Pradhan, N., et al., Qian, F., Rookus, Matti A., Leslie, G., Risch, H.A., Greene, M.H., Aalfs, C.M., Adank, M.A., Adlard, J., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Andrulis, I.L., Arnold, N., Arun, B.K., Ausems, M., Azzollini, J., Barrowdale, D., Barwell, J., Benitez, J., Bialkowska, K., Bonadona, V., Borde, J., Borg, A., Bradbury, A.R., Brunet, J., Buys, S.S., Caldes, T., Caligo, M.A., Campbell, I., Carter, J., Chiquette, J., Chung, W.K., Claes, K.B.M., Collee, J.M., Collonge-Rame, M.A., Couch, F.J., Daly, M.B., Delnatte, C., Diez, O., Domchek, S.M., Dorfling, C.M., Eason, J., Easton, D.F., Eeles, R., Engel, C., Evans, D.G., Faivre, L., Feliubadalo, L., Foretova, L., Friedman, E., Frost, D., Ganz, P.A., Garber, J., Garcia-Barberan, V., Gehrig, A., Glendon, G., Godwin, A.K., Garcia, E.B., Hamann, U., Hauke, J., Hopper, J.L., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., Janavicius, R., John, E.M., Karlan, B.Y., Kets, C.M., Laitman, Y., Lazaro, C., Leroux, D., Lester, J., Lesueur, F., Loud, J.T., Lubinski, J., Lukomska, A., McGuffog, L., Mebirouk, N., Meijers-Heijboer, H.E., Meindl, A., Miller, A., Montagna, M., Mooij, T.M., Mouret-Fourme, E., Nathanson, K.L., Nehoray, B., Neuhausen, S.L., Nevanlinna, H., Nielsen, F.C., Offit, K., Olah, E., Ong, K.R., Oosterwijk, J.C, Ottini, L., Parsons, M.T., Peterlongo, P., Pfeiler, G., and Pradhan, N., et al.
Abstract: Contains fulltext : 208524.pdf (publisher's version ) (Open Access), BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.
Published: 2019

21. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Author: Boutry-Kryza N., Rantala J., Rashid M.U., Rau-Murthy R., Rennert G., Lejbkowicz F., Rhenius V., Romero A., Rookus M.A., Ross E.A., Rossing M., Rudaitis V., Ruebner M., Saloustros E., Sanden K., Santamarina M., Scheuner M.T., Schmutzler R.K., Schneider M., Scott C., Senter L., Shah M., Sharma P., Shu X.-O., Simard J., Singer C.F., Sohn C., Soucy P., Southey M.C., Spinelli J.J., Steele L., Stoppa-Lyonnet D., Tapper W.J., Teixeira M.R., Terry M.B., Thomassen M., Thompson J., Thull D.L., Tischkowitz M., Tollenaar R.A.E.M., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van Rensburg E.J., van Veen E.M., Vega A., Viel A., Wappenschmidt B., Weitzel J.N., Wendt C., Wieme G., Wolk A., Yang X.R., Zheng W., Ziogas A., Zorn K.K., Dunning A.M., Lush M., Wang Q., McGuffog L., Parsons M.T., Pharoah P.D.P., Fostira F., Toland A.E., Andrulis I.L., Ramus S.J., Swerdlow A.J., Greene M.H., Chung W.K., Milne R.L., Chenevix-Trench G., Dork T., Schmidt M.K., Easton D.F., Radice P., Hahnen E., Antoniou A.C., Couch F.J., Nevanlinna H., Surralles J., Peterlongo P., Harris M., Figlioli G., Bogliolo M., Catucci I., Caleca L., Lasheras S.V., Pujol R., Kiiski J.I., Muranen T.A., Barnes D.R., Dennis J., Michailidou K., Bolla M.K., Leslie G., Aalfs C.M., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee C.S., Marsh D., Morey A., Pathmanathan N., Scott R., Simpson P., Spigelman A., Wilcken N., Yip D., Zeps N., Adank M.A., Adlard J., Agata S., Cadoo K., Agnarsson B.A., Ahearn T., Aittomaki K., Ambrosone C.B., Andrews L., Anton-Culver H., Antonenkova N.N., Arndt V., Arnold N., Aronson K.J., Arun B.K., Asseryanis E., Auber B., Auvinen P., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Beane Freeman L.E., Beauparlant C.J., Beckmann M.W., Behrens S., Benitez J., Berger R., Bermisheva M., Blanco A.M., Blomqvist C., Bogdanova N.V., Bojesen A., Bojesen S.E., Bonanni B., Borg A., Brady A.F., Brauch H., Brenner H., Bruning T., Burwinkel B., Buys S.S., Caldes T., Caliebe A., Caligo M.A., Campa D., Campbell I.G., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Claes K.B.M., Clarke C.L., Collavoli A., Conner T.A., Cox D.G., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Ditsch N., Domchek S.M., Dorfling C.M., dos-Santos-Silva I., Durda K., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Ellberg C., Eriksson M., Evans D.G., Fasching P.A., Figueroa J., Flyger H., Foulkes W.D., Friebel T.M., Friedman E., Gabrielson M., Gaddam P., Gago-Dominguez M., Gao C., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Belotti M., Bertrand O., Birot A.-M., Buecher B., Caputo S., Dupre A., Fourme E., Gauthier-Villars M., Golmard L., Le Mentec M., Moncoutier V., de Pauw A., Saule C., Calender A., Giraud S., Leone M., Bressac-de-Paillerets B., Caron O., Guillaud-Bataille M., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Berthet P., Castera L., Vaur D., Bourdon V., Nogues C., Noguchi T., Popovici C., Remenieras A., Sobol H., Coupier I., Pujol P., Adenis C., Dumont A., Revillion F., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Longy M., Sevenet N., Gladieff L., Guimbaud R., Feillel V., Toulas C., Dreyfus H., Leroux C.D., Peysselon M., Rebischung C., Legrand C., Baurand A., Bertolone G., Coron F., Faivre L., Jacquot C., Lizard S., Kientz C., Lebrun M., Prieur F., Fert-Ferrer S., Mari V., Venat-Bouvet L., Bezieau S., Delnatte C., Mortemousque I., Colas C., Coulet F., Soubrier F., Warcoin M., Bronner M., Sokolowska J., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Manouvrier-Hanu S., Lejeune S., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Guenel P., Gutierrez-Barrera A.M., Haeberle L., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hein A., Heyworth J., Hillemanns P., Hollestelle A., Hopper J.L., Hosgood H.D., Howell A., Hu C., Hulick P.J., Hunter D.J., Imyanitov E.N., Aghmesheh M., Greening S., Amor D., Gattas M., Botes L., Buckley M., Friedlander M., Koehler J., Meiser B., Saleh M., Salisbury E., Trainer A., Tucker K., Antill Y., Dobrovic A., Fellows A., Fox S., Nightingale S., Phillips K., Sambrook J., Thorne H., Armitage S., Arnold L., Kefford R., Kirk J., Rickard E., Bastick P., Beesley J., Hayward N., Spurdle A., Walker L., Beilby J., Saunders C., Bennett I., Blackburn A., Bogwitz M., Gaff C., Lindeman G., Pachter N., Sexton A., Visvader J., Taylor J., Winship I., Brennan M., Brown M., French J., Edwards S., Burgess M., Burke J., Patterson B., Butow P., Culling B., Caldon L., Callen D., Chauhan D., Eisenbruch M., Heiniger L., Chauhan M., Christian A., Dixon J., Kidd A., Cohen P., Colley A., Fenton G., Crook A., Dickson R., Field M., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dudding T., Edkins T., Farshid G., Flanagan J., Fong P., Forrest L., Gallego-Ortega D., George P., Gill G., Kollias J., Haan E., Hart S., Jenkins M., Hunt C., Lakhani S., Lipton L., Lobb L., Mann G., McLachlan S.A., O'Connell S., O'Sullivan S., Pieper E., Robinson B., Saunus J., Scott E., Shelling A., Williams R., Young M.A., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Karlan B.Y., Khusnutdinova E., Kitahara C.M., Konstantopoulou I., Koutros S., Kraft P., Lambrechts D., Lazaro C., Le Marchand L., Lester J., Lesueur F., Lilyquist J., Loud J.T., Lu K.H., Luben R.N., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Maurer T., Mavroudis D., Mebirouk N., Meindl A., Menon U., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Newman W.G., Nguyen-Dumont T., Nielsen F.C., Nielsen S., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olshan A.F., Olson J.E., Olsson H., Osorio A., Ottini L., Peissel B., Peixoto A., Peto J., Plaseska-Karanfilska D., Pocza T., Presneau N., Pujana M.A., Punie K., Rack B., Boutry-Kryza N., Rantala J., Rashid M.U., Rau-Murthy R., Rennert G., Lejbkowicz F., Rhenius V., Romero A., Rookus M.A., Ross E.A., Rossing M., Rudaitis V., Ruebner M., Saloustros E., Sanden K., Santamarina M., Scheuner M.T., Schmutzler R.K., Schneider M., Scott C., Senter L., Shah M., Sharma P., Shu X.-O., Simard J., Singer C.F., Sohn C., Soucy P., Southey M.C., Spinelli J.J., Steele L., Stoppa-Lyonnet D., Tapper W.J., Teixeira M.R., Terry M.B., Thomassen M., Thompson J., Thull D.L., Tischkowitz M., Tollenaar R.A.E.M., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van Rensburg E.J., van Veen E.M., Vega A., Viel A., Wappenschmidt B., Weitzel J.N., Wendt C., Wieme G., Wolk A., Yang X.R., Zheng W., Ziogas A., Zorn K.K., Dunning A.M., Lush M., Wang Q., McGuffog L., Parsons M.T., Pharoah P.D.P., Fostira F., Toland A.E., Andrulis I.L., Ramus S.J., Swerdlow A.J., Greene M.H., Chung W.K., Milne R.L., Chenevix-Trench G., Dork T., Schmidt M.K., Easton D.F., Radice P., Hahnen E., Antoniou A.C., Couch F.J., Nevanlinna H., Surralles J., Peterlongo P., Harris M., Figlioli G., Bogliolo M., Catucci I., Caleca L., Lasheras S.V., Pujol R., Kiiski J.I., Muranen T.A., Barnes D.R., Dennis J., Michailidou K., Bolla M.K., Leslie G., Aalfs C.M., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee C.S., Marsh D., Morey A., Pathmanathan N., Scott R., Simpson P., Spigelman A., Wilcken N., Yip D., Zeps N., Adank M.A., Adlard J., Agata S., Cadoo K., Agnarsson B.A., Ahearn T., Aittomaki K., Ambrosone C.B., Andrews L., Anton-Culver H., Antonenkova N.N., Arndt V., Arnold N., Aronson K.J., Arun B.K., Asseryanis E., Auber B., Auvinen P., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Barwell J., Beane Freeman L.E., Beauparlant C.J., Beckmann M.W., Behrens S., Benitez J., Berger R., Bermisheva M., Blanco A.M., Blomqvist C., Bogdanova N.V., Bojesen A., Bojesen S.E., Bonanni B., Borg A., Brady A.F., Brauch H., Brenner H., Bruning T., Burwinkel B., Buys S.S., Caldes T., Caliebe A., Caligo M.A., Campa D., Campbell I.G., Canzian F., Castelao J.E., Chang-Claude J., Chanock S.J., Claes K.B.M., Clarke C.L., Collavoli A., Conner T.A., Cox D.G., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Ditsch N., Domchek S.M., Dorfling C.M., dos-Santos-Silva I., Durda K., Dwek M., Eccles D.M., Ekici A.B., Eliassen A.H., Ellberg C., Eriksson M., Evans D.G., Fasching P.A., Figueroa J., Flyger H., Foulkes W.D., Friebel T.M., Friedman E., Gabrielson M., Gaddam P., Gago-Dominguez M., Gao C., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Belotti M., Bertrand O., Birot A.-M., Buecher B., Caputo S., Dupre A., Fourme E., Gauthier-Villars M., Golmard L., Le Mentec M., Moncoutier V., de Pauw A., Saule C., Calender A., Giraud S., Leone M., Bressac-de-Paillerets B., Caron O., Guillaud-Bataille M., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Berthet P., Castera L., Vaur D., Bourdon V., Nogues C., Noguchi T., Popovici C., Remenieras A., Sobol H., Coupier I., Pujol P., Adenis C., Dumont A., Revillion F., Muller D., Barouk-Simonet E., Bonnet F., Bubien V., Longy M., Sevenet N., Gladieff L., Guimbaud R., Feillel V., Toulas C., Dreyfus H., Leroux C.D., Peysselon M., Rebischung C., Legrand C., Baurand A., Bertolone G., Coron F., Faivre L., Jacquot C., Lizard S., Kientz C., Lebrun M., Prieur F., Fert-Ferrer S., Mari V., Venat-Bouvet L., Bezieau S., Delnatte C., Mortemousque I., Colas C., Coulet F., Soubrier F., Warcoin M., Bronner M., Sokolowska J., Collonge-Rame M.-A., Damette A., Gesta P., Lallaoui H., Chiesa J., Molina-Gomes D., Ingster O., Manouvrier-Hanu S., Lejeune S., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Guenel P., Gutierrez-Barrera A.M., Haeberle L., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hein A., Heyworth J., Hillemanns P., Hollestelle A., Hopper J.L., Hosgood H.D., Howell A., Hu C., Hulick P.J., Hunter D.J., Imyanitov E.N., Aghmesheh M., Greening S., Amor D., Gattas M., Botes L., Buckley M., Friedlander M., Koehler J., Meiser B., Saleh M., Salisbury E., Trainer A., Tucker K., Antill Y., Dobrovic A., Fellows A., Fox S., Nightingale S., Phillips K., Sambrook J., Thorne H., Armitage S., Arnold L., Kefford R., Kirk J., Rickard E., Bastick P., Beesley J., Hayward N., Spurdle A., Walker L., Beilby J., Saunders C., Bennett I., Blackburn A., Bogwitz M., Gaff C., Lindeman G., Pachter N., Sexton A., Visvader J., Taylor J., Winship I., Brennan M., Brown M., French J., Edwards S., Burgess M., Burke J., Patterson B., Butow P., Culling B., Caldon L., Callen D., Chauhan D., Eisenbruch M., Heiniger L., Chauhan M., Christian A., Dixon J., Kidd A., Cohen P., Colley A., Fenton G., Crook A., Dickson R., Field M., Cui J., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dudding T., Edkins T., Farshid G., Flanagan J., Fong P., Forrest L., Gallego-Ortega D., George P., Gill G., Kollias J., Haan E., Hart S., Jenkins M., Hunt C., Lakhani S., Lipton L., Lobb L., Mann G., McLachlan S.A., O'Connell S., O'Sullivan S., Pieper E., Robinson B., Saunus J., Scott E., Shelling A., Williams R., Young M.A., Isaacs C., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Karlan B.Y., Khusnutdinova E., Kitahara C.M., Konstantopoulou I., Koutros S., Kraft P., Lambrechts D., Lazaro C., Le Marchand L., Lester J., Lesueur F., Lilyquist J., Loud J.T., Lu K.H., Luben R.N., Lubinski J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martens J.W.M., Maurer T., Mavroudis D., Mebirouk N., Meindl A., Menon U., Miller A., Montagna M., Nathanson K.L., Neuhausen S.L., Newman W.G., Nguyen-Dumont T., Nielsen F.C., Nielsen S., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Olshan A.F., Olson J.E., Olsson H., Osorio A., Ottini L., Peissel B., Peixoto A., Peto J., Plaseska-Karanfilska D., Pocza T., Presneau N., Pujana M.A., Punie K., and Rack B.
Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM-/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.Copyright © 2019, The Author(s).
Published: 2019

22. Shared heritability and functional enrichment across six solid cancers.

Author: Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tangen C.M., Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., and Tangen C.M.
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 x 10-8), breast and ovarian cancer (rg = 0.24, p = 7 x 10-5), breast and lung cancer (rg = 0.18, p =1.5 x 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 x 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Copyright © 2019, The Author(s).
Published: 2019

23. Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4).

Author: Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., and Wu A.H.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.Copyright © 2019, The Author(s).
Published: 2019

24. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Author: Herold N., Rantala J., Rennert G., Risch H.A., Saloustros E., Sanden K., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Sharma P., Shu X.-O., Simard J., Singer C.F., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Wang Q., Wappenschmidt B., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Kraft P., Antoniou A.C., Zheng W., Easton D.F., Milne R.L., Beesley J., Chenevix-Trench G., Ferreira M.A., Gamazon E.R., Al-Ejeh F., Aittomaki K., Andrulis I.L., Anton-Culver H., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Azzollini J., Balmana J., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bolla M.K., Borg A., Brauch H., Brenner H., Broeks A., Burwinkel B., Caldes T., Caligo M.A., Campa D., Campbell I., Canzian F., Carter J., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Adlard J., Ahmed M., Barwell J., Brady A., Brewer C., Cook J., Davidson R., Donaldson A., Eason J., Eeles R., Evans D.G., Gregory H., Hanson H., Henderson A., Hodgson S., Izatt L., Kennedy M.J., Lalloo F., Miller C., Morrison P.J., Ong K.-R., Perkins J., Porteous M.E., Rogers M.T., Side L.E., Snape K., Walker L., Harrington P.A., Arnold N., Auber B., Bogdanova-Markov N., Borde J., Caliebe A., Ditsch N., Dworniczak B., Engert S., Faust U., Gehrig A., Hahnen E., Hauke J., Hentschel J., Honisch E., Just W., Kast K., Larsen M., Lemke J., Nguyen H.P., Niederacher D., Ott C.-E., Platzer K., Pohl-Rescigno E., Ramser J., Rhiem K., Steinemann D., Sutter C., Varon-Mateeva R., Wang-Gohrke S., Weber B.H.F., Prieur F., Pujol P., Sagne C., Sevenet N., Sobol H., Sokolowska J., Stoppa-Lyonnet D., Venat-Bouvet L., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., de la Hoya M., Dennis J., Devilee P., Diez O., Dork T., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Eriksson M., Fasching P.A., Fletcher O., Flyger H., Friedman E., Frost D., Gabrielson M., Gago-Dominguez M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hoover R.N., Hopper J.L., Hulick P.J., Humphreys K., Imyanitov E.N., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee S.C., Marsh D., Morey A., Pathmanathan N., Simpson P., Spigelman A., Wilcken N., Yip D., Heemskerk-Gerritsen B.A.M., Rookus M.A., Seynaeve C.M., van der Baan F.H., van der Hout A.H., van der Kolk L.E., van der Luijt R.B., van Deurzen C.H.M., van Doorn H.C., van Engelen K., van Hest L., van Os T.A.M., Verhoef S., Vogel M.J., Wijnen J.T., Miron A., Kapuscinski M., Bane A., Ross E., Buys S.S., Conner T.A., Isaacs C., Jakimovska M., Jakubowska A., James P.A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Jones M.E., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leslie G., Lester J., Lesueur F., Lindstrom S., Long J., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Margolin S., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Nussbaum R.L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peixoto A., Peterlongo P., Pharoah P.D.P., Plaseska-Karanfilska D., Poppe B., Presneau N., Radice P., Herold N., Rantala J., Rennert G., Risch H.A., Saloustros E., Sanden K., Sawyer E.J., Schmidt M.K., Schmutzler R.K., Sharma P., Shu X.-O., Simard J., Singer C.F., Soucy P., Southey M.C., Spinelli J.J., Spurdle A.B., Stone J., Swerdlow A.J., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Teule A., Thomassen M., Thone K., Thull D.L., Tischkowitz M., Toland A.E., Torres D., Truong T., Tung N., Vachon C.M., van Asperen C.J., van den Ouweland A.M.W., van Rensburg E.J., Vega A., Viel A., Wang Q., Wappenschmidt B., Weitzel J.N., Wendt C., Winqvist R., Yang X.R., Yannoukakos D., Ziogas A., Kraft P., Antoniou A.C., Zheng W., Easton D.F., Milne R.L., Beesley J., Chenevix-Trench G., Ferreira M.A., Gamazon E.R., Al-Ejeh F., Aittomaki K., Andrulis I.L., Anton-Culver H., Arason A., Arndt V., Aronson K.J., Arun B.K., Asseryanis E., Azzollini J., Balmana J., Barnes D.R., Barrowdale D., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bolla M.K., Borg A., Brauch H., Brenner H., Broeks A., Burwinkel B., Caldes T., Caligo M.A., Campa D., Campbell I., Canzian F., Carter J., Carter B.D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Adlard J., Ahmed M., Barwell J., Brady A., Brewer C., Cook J., Davidson R., Donaldson A., Eason J., Eeles R., Evans D.G., Gregory H., Hanson H., Henderson A., Hodgson S., Izatt L., Kennedy M.J., Lalloo F., Miller C., Morrison P.J., Ong K.-R., Perkins J., Porteous M.E., Rogers M.T., Side L.E., Snape K., Walker L., Harrington P.A., Arnold N., Auber B., Bogdanova-Markov N., Borde J., Caliebe A., Ditsch N., Dworniczak B., Engert S., Faust U., Gehrig A., Hahnen E., Hauke J., Hentschel J., Honisch E., Just W., Kast K., Larsen M., Lemke J., Nguyen H.P., Niederacher D., Ott C.-E., Platzer K., Pohl-Rescigno E., Ramser J., Rhiem K., Steinemann D., Sutter C., Varon-Mateeva R., Wang-Gohrke S., Weber B.H.F., Prieur F., Pujol P., Sagne C., Sevenet N., Sobol H., Sokolowska J., Stoppa-Lyonnet D., Venat-Bouvet L., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., de la Hoya M., Dennis J., Devilee P., Diez O., Dork T., Dunning A.M., Dwek M., Eccles D.M., Ejlertsen B., Ellberg C., Engel C., Eriksson M., Fasching P.A., Fletcher O., Flyger H., Friedman E., Frost D., Gabrielson M., Gago-Dominguez M., Ganz P.A., Gapstur S.M., Garber J., Garcia-Closas M., Garcia-Saenz J.A., Gaudet M.M., Giles G.G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haiman C.A., Hall P., Hamann U., He W., Heyworth J., Hogervorst F.B.L., Hollestelle A., Hoover R.N., Hopper J.L., Hulick P.J., Humphreys K., Imyanitov E.N., Balleine R., Baxter R., Braye S., Carpenter J., Dahlstrom J., Forbes J., Lee S.C., Marsh D., Morey A., Pathmanathan N., Simpson P., Spigelman A., Wilcken N., Yip D., Heemskerk-Gerritsen B.A.M., Rookus M.A., Seynaeve C.M., van der Baan F.H., van der Hout A.H., van der Kolk L.E., van der Luijt R.B., van Deurzen C.H.M., van Doorn H.C., van Engelen K., van Hest L., van Os T.A.M., Verhoef S., Vogel M.J., Wijnen J.T., Miron A., Kapuscinski M., Bane A., Ross E., Buys S.S., Conner T.A., Isaacs C., Jakimovska M., Jakubowska A., James P.A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Joseph V., Karlan B.Y., Khusnutdinova E., Kiiski J.I., Ko Y.-D., Jones M.E., Konstantopoulou I., Kristensen V.N., Laitman Y., Lambrechts D., Lazaro C., Leslie G., Lester J., Lesueur F., Lindstrom S., Long J., Loud J.T., Lubinski J., Makalic E., Mannermaa A., Manoochehri M., Margolin S., Maurer T., Mavroudis D., McGuffog L., Meindl A., Menon U., Michailidou K., Miller A., Montagna M., Moreno F., Moserle L., Mulligan A.M., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Nevelsteen I., Nielsen F.C., Nikitina-Zake L., Nussbaum R.L., Offit K., Olah E., Olopade O.I., Olsson H., Osorio A., Papp J., Park-Simon T.-W., Parsons M.T., Pedersen I.S., Peixoto A., Peterlongo P., Pharoah P.D.P., Plaseska-Karanfilska D., Poppe B., Presneau N., and Radice P.
Abstract: Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Copyright © 2019, The Author(s).
Published: 2019

25. Copenhagen prospective personalized oncology (CoPPO): Genomic profiling to select patients for phase 1 trials

Author: Tuxen, I.V., primary, Yde, C.W., additional, Mau-Sørensen, M., additional, Santoni-Rugiu, E., additional, Lassen, U., additional, and Nielsen, F.C., additional
Published: 2016
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26. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

Author: Blein, S., Bardel, C., Danjean, V., McGuffog, L., Healey, S., Barrowdale, D., Lee, A., Dennis, J., Kuchenbaecker, K.B., Soucy, P., Terry, M.B., Chung, W.K., Goldgar, D.E., Buys, S.S., Janavicius, R., Tihomirova, L., Tung, N., Dorfling, C.M., Rensburg, E.J. van, Neuhausen, S.L., Ding, Y.C., Gerdes, A.M., Ejlertsen, B., Nielsen, F.C., Hansen, T.V., Osorio, A., Benitez, J., Conejero, R.A., Segota, E., Weitzel, J.N., Thelander, M., Peterlongo, P., Radice, P., Pensotti, V., Dolcetti, R., Bonanni, B., Peissel, B., Zaffaroni, D., Scuvera, G., Manoukian, S., Varesco, L., Capone, G.L., Papi, L., Ottini, L., Yannoukakos, D., Konstantopoulou, I., Garber, J., Hamann, U., Donaldson, A., Brady, A., Brewer, C., Foo, C., Evans, D.G., Frost, D., Eccles, D., Douglas, F., Cook, J., Adlard, J., Barwell, J., Walker, L., Izatt, L., Side, L.E., Kennedy, M.J., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Morrison, P.J., Platte, R., Eeles, R., Davidson, R., Hodgson, S., Cole, T., Godwin, A.K., Isaacs, C., Claes, K., Leeneer, K. De, Meindl, A., Gehrig, A., Wappenschmidt, B., Sutter, C., Engel, C., Niederacher, D., Steinemann, D., Plendl, H., Kast, K., Rhiem, K., Ditsch, N., Arnold, N., Varon-Mateeva, R., Schmutzler, R.K., Preisler-Adams, S., Markov, N.B., Wang-Gohrke, S., Pauw, A. de, Lefol, C., Lasset, C., Leroux, D., Rouleau, E., Damiola, F., Dreyfus, H., Barjhoux, L., Golmard, L., Uhrhammer, N., Bonadona, V., Sornin, V., Bignon, Y.J., Carter, J., Le, L, Piedmonte, M., DiSilvestro, P.A., Hoya, M. de la, Caldes, T., Nevanlinna, H., Aittomaki, K., Jager, A., Ouweland, A.M. van den, Kets, C.M., Aalfs, C.M., Leeuwen, F.E. van, Hogervorst, F.B., Meijers-Heijboer, H.E., Oosterwijk, J.C., Roozendaal, K.E. van, Rookus, M.A., Devilee, P., Luijt, R.B. van der, Olah, E., Diez, O., Teule, A., Lazaro, C., Blanco, I., Valle, J., Jakubowska, A., Sukiennicki, G., Gronwald, J., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Agnarsson, B.A., Maugard, C., Amadori, A., Montagna, M., Teixeira, M.R., Spurdle, A.B., Foulkes, W., Olswold, C., Lindor, N.M., Pankratz, V.S., Szabo, C.I., Lincoln, A., Jacobs, L., Corines, M., Robson, M., Vijai, J., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Kaulich, D.G., Pfeiler, G., Tea, M.K., Greene, M.H., Mai, P.L., Rennert, G., Imyanitov, E.N., Mulligan, A.M., Glendon, G., Andrulis, I.L., Tchatchou, S., Toland, A.E., Pedersen, I.S., Thomassen, M., Kruse, T.A., Jensen, U.B., Caligo, M.A., Friedman, E., Zidan, J., Laitman, Y., Lindblom, A., Melin, B., Arver, B., Loman, N., Rosenquist, R., Olopade, O.I., Nussbaum, R.L., Ramus, S.J., Nathanson, K.L., Domchek, S.M., Rebbeck, T.R., Arun, B.K., Mitchell, G., Karlan, B.Y., Lester, J., Orsulic, S., Stoppa-Lyonnet, D., Thomas, G, Simard, J., Couch, F.J., Offit, K., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., Mazoyer, S., Phelan, C.M., Sinilnikova, O.M., Cox, D.G., Blein, S., Bardel, C., Danjean, V., McGuffog, L., Healey, S., Barrowdale, D., Lee, A., Dennis, J., Kuchenbaecker, K.B., Soucy, P., Terry, M.B., Chung, W.K., Goldgar, D.E., Buys, S.S., Janavicius, R., Tihomirova, L., Tung, N., Dorfling, C.M., Rensburg, E.J. van, Neuhausen, S.L., Ding, Y.C., Gerdes, A.M., Ejlertsen, B., Nielsen, F.C., Hansen, T.V., Osorio, A., Benitez, J., Conejero, R.A., Segota, E., Weitzel, J.N., Thelander, M., Peterlongo, P., Radice, P., Pensotti, V., Dolcetti, R., Bonanni, B., Peissel, B., Zaffaroni, D., Scuvera, G., Manoukian, S., Varesco, L., Capone, G.L., Papi, L., Ottini, L., Yannoukakos, D., Konstantopoulou, I., Garber, J., Hamann, U., Donaldson, A., Brady, A., Brewer, C., Foo, C., Evans, D.G., Frost, D., Eccles, D., Douglas, F., Cook, J., Adlard, J., Barwell, J., Walker, L., Izatt, L., Side, L.E., Kennedy, M.J., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Morrison, P.J., Platte, R., Eeles, R., Davidson, R., Hodgson, S., Cole, T., Godwin, A.K., Isaacs, C., Claes, K., Leeneer, K. De, Meindl, A., Gehrig, A., Wappenschmidt, B., Sutter, C., Engel, C., Niederacher, D., Steinemann, D., Plendl, H., Kast, K., Rhiem, K., Ditsch, N., Arnold, N., Varon-Mateeva, R., Schmutzler, R.K., Preisler-Adams, S., Markov, N.B., Wang-Gohrke, S., Pauw, A. de, Lefol, C., Lasset, C., Leroux, D., Rouleau, E., Damiola, F., Dreyfus, H., Barjhoux, L., Golmard, L., Uhrhammer, N., Bonadona, V., Sornin, V., Bignon, Y.J., Carter, J., Le, L, Piedmonte, M., DiSilvestro, P.A., Hoya, M. de la, Caldes, T., Nevanlinna, H., Aittomaki, K., Jager, A., Ouweland, A.M. van den, Kets, C.M., Aalfs, C.M., Leeuwen, F.E. van, Hogervorst, F.B., Meijers-Heijboer, H.E., Oosterwijk, J.C., Roozendaal, K.E. van, Rookus, M.A., Devilee, P., Luijt, R.B. van der, Olah, E., Diez, O., Teule, A., Lazaro, C., Blanco, I., Valle, J., Jakubowska, A., Sukiennicki, G., Gronwald, J., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Agnarsson, B.A., Maugard, C., Amadori, A., Montagna, M., Teixeira, M.R., Spurdle, A.B., Foulkes, W., Olswold, C., Lindor, N.M., Pankratz, V.S., Szabo, C.I., Lincoln, A., Jacobs, L., Corines, M., Robson, M., Vijai, J., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Kaulich, D.G., Pfeiler, G., Tea, M.K., Greene, M.H., Mai, P.L., Rennert, G., Imyanitov, E.N., Mulligan, A.M., Glendon, G., Andrulis, I.L., Tchatchou, S., Toland, A.E., Pedersen, I.S., Thomassen, M., Kruse, T.A., Jensen, U.B., Caligo, M.A., Friedman, E., Zidan, J., Laitman, Y., Lindblom, A., Melin, B., Arver, B., Loman, N., Rosenquist, R., Olopade, O.I., Nussbaum, R.L., Ramus, S.J., Nathanson, K.L., Domchek, S.M., Rebbeck, T.R., Arun, B.K., Mitchell, G., Karlan, B.Y., Lester, J., Orsulic, S., Stoppa-Lyonnet, D., Thomas, G, Simard, J., Couch, F.J., Offit, K., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., Mazoyer, S., Phelan, C.M., Sinilnikova, O.M., and Cox, D.G.
Abstract: Contains fulltext : 156875.pdf (publisher's version ) (Open Access), INTRODUCTION: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. METHODS: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. RESULTS: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. CONCLUSIONS: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effe
Published: 2015

27. Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Author: Mavaddat, N., Barrowdale, D., Andrulis, I.L., Domchek, S.M., Eccles, D., Nevanlinna, H., Ramus, S.J., Spurdle, A., Robson, M., Sherman, M., Mulligan, A.M., Couch, F.J., Engel, C., McGuffog, L., Healey, S., Sinilnikova, O.M., Southey, M.C., Terry, M.B., Goldgar, D., O'Malley, F., John, E.M., Janavicius, R., Tihomirova, L., Hansen, T.V.O., Nielsen, F.C., Osorio, A., Stavropoulou, A., Benitez, J., Manoukian, S., Peissel, B., Barile, M., Volorio, S., Pasini, B., Dolcetti, R., Putignano, A.L., Ottini, L., Radice, P., Hamann, U., Rashid, M.U., Hogervorst, F.B., Kriege, M., Luijt, R.B. van der, Peock, S., Frost, D., Evans, D.G., Brewer, C., Walker, L., Rogers, M.T., Side, L.E., Houghton, C., Weaver, J., Godwin, A.K., Schmutzler, R.K., Wappenschmidt, B., Meindl, A., Kast, K., Arnold, N., Niederacher, D., Sutter, C., Deissler, H., Gadzicki, D., Preisler-Adams, S., Varon-Mateeva, R., Schonbuchner, I., Gevensleben, H., Stoppa-Lyonnet, D., Belotti, M., Barjhoux, L., Isaacs, C., Peshkin, B.N., Caldes, T., Hoya, M. de la, Canadas, C., Heikkinen, T., Heikkila, P., Aittomaki, K., Blanco, I., Lazaro, C., Brunet, J., Agnarsson, B.A., Arason, A., Barkardottir, R.B., Dumont, M., Simard, J., Montagna, M., Agata, S., D'Andrea, E., Yan, M., Fox, S., Rebbeck, T.R., Rubinstein, W., Tung, N., Garber, J.E., Wang, X.S., Fredericksen, Z., Pankratz, V.S., Lindor, N.M., Szabo, C., Offit, K., Sakr, R., Gaudet, M.M., Singer, C.F., Tea, M.K., Rappaport, C., Mai, P.L., Greene, M.H., Sokolenko, A., Imyanitov, E., Toland, A.E., Senter, L., Sweet, K., Thomassen, M., Gerdes, A.M., Kruse, T., Caligo, M., Aretini, P., Rantala, J., Wachenfeld, A. von, Henriksson, K., Steele, L., Neuhausen, S.L., Nussbaum, R., Beattie, M., Odunsi, K., Sucheston, L., Gayther, S.A., Nathanson, K., Gross, J., Walsh, C., Karlan, B., Chenevix-Trench, G., Easton, D.F., Antoniou, A.C., HEBON, EMBRACE, GEMO Study Collaborators, kConFab Investigators, SWE-BRCA Collaborators, Consortium Investigators Modifiers, Medical Oncology, Clinical Genetics, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, and RS: GROW - School for Oncology and Reproduction
Subjects: Oncology, Pathology, endocrine system diseases, Epidemiology, Genes, BRCA2, Genes, BRCA1, Estrogen receptor, Gene mutation, 0302 clinical medicine, Cancer screening, Medicine, skin and connective tissue diseases, Estrogen Receptor Status, Ovarian Neoplasms, 0303 health sciences, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, triple-negative tumors, 030220 oncology & carcinogenesis, Female, estrogen receptor, Adult, medicine.medical_specialty, BRCA1, BRCA2, breast cancer, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Breast Neoplasms, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], Internal medicine, Humans, Genetic Predisposition to Disease, Genetics and epigenetic pathways of disease Translational research [NCMLS 6], Germ-Line Mutation, Aged, 030304 developmental biology, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Cancer, medicine.disease, Neoplasm Grading, business, Ovarian cancer
Abstract: Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. Results: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10−5), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10−6). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10−13 for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0–12.6 and PR-positive OR = 1.7, 95% CI: 1.3–2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4–4.4; P = 4.4 × 10−14), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18–0.35; P = 2.3 × 10−15). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 21(1); 134–47. ©2011 AACR.
Published: 2012

28. Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Couch, F.J., Gaudet, M.M., Antoniou, A.C., Ramus, S.J., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X.Q., Wang, X.S., Kirchhoff, T., McGuffog, L., Barrowdale, D., Lee, A., Healey, S., Sinilnikova, O.M., Andrulis, I.L., Ozcelik, H., Mulligan, A.M., Thomassen, M., Gerdes, A.M., Jensen, U.B., Skytte, A.B., Kruse, T.A., Caligo, M.A., Wachenfeldt, A. von, Barbany-Bustinza, G., Loman, N., Soller, M., Ehrencrona, H., Karlsson, P., Nathanson, K.L., Rebbeck, T.R., Domchek, S.M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Huzarski, T., Byrski, T., Gronwald, J., Cybulski, C., Gorski, B., Osorio, A., Duran, M., Tejada, M.I., Benitez, J., Hamann, U., Hogervorst, F.B.L., Os, T.A. van, Leeuwen, F.E. van, Meijers-Heijboer, H.E.J., Wijnen, J., Blok, M.J., Kets, M., Hooning, M.J., Oldenburg, R.A., Ausems, M.G.E.M., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Jacobs, C., Eeles, R.A., Adlard, J., Davidson, R., Eccles, D.M., Cole, T., Cook, J., Paterson, J., Brewer, C., Douglas, F., Hodgson, S.V., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Side, L.E., Bove, B., Godwin, A.K., Stoppa-Lyonnet, D., Fassy-Colcombet, M., Castera, L., Cornelis, F., Mazoyer, S., Leone, M., Boutry-Kryza, N., Bressac-de Paillerets, B., Caron, O., Pujol, P., Coupier, I., Delnatte, C., Akloul, L., Lynch, H.T., Snyder, C.L., Buys, S.S., Daly, M.B., Terry, M., Chung, W.K., John, E.M., Miron, A., Southey, M.C., Hopper, J.L., Goldgar, D.E., Singer, C.F., Rappaport, C., Tea, M.K.M., Fink-Retter, A., Hansen, T.V.O., Nielsen, F.C., Arason, A., Vijai, J., Shah, S., Sarrel, K., Robson, M.E., Piedmonte, M., Phillips, K., Basil, J., Rubinstein, W.S., Boggess, J., Wakeley, K., Ewart-Toland, A., Montagna, M., Agata, S., Imyanitov, E.N., Isaacs, C., Janavicius, R., Lazaro, C., Blanco, I., Feliubadalo, L., Brunet, J., Gayther, S.A., Pharoah, P.P.D., Odunsi, K.O., Karlan, B.Y., Walsh, C.S., Olah, E., Teo, S.H., Ganz, P.A., Beattie, M.S., Rensburg, E.J. van, Dorfling, C.M., Diez, O., Kwong, A., Schmutzler, R.K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Heidemann, S., Niederacher, D., Preisler-Adams, S., Gadzicki, D., Varon-Mateeva, R., Deissler, H., Gehrig, A., Sutter, C., Kast, K., Fiebig, B., Heinritz, W., Caldes, T., Hoya, M. de la, Muranen, T.A., Nevanlinna, H., Tischkowitz, M., Spurdle, A.B., Neuhausen, S.L., Ding, Y.C., Lindor, N.M., Fredericksen, Z., Pankratz, V.S., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Barile, M., Bernard, L., Viel, A., Giannini, G., Varesco, L., Radice, P., Greene, M.H., Mai, P.L., Easton, D.F., Chenevix-Trench, G., Offit, K., Simard, J., OCGN, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, kConFab Investigators, Consortium Investigators Modifiers, European Commission, National Institutes of Health (US), Breast Cancer Research Foundation, Cancer Research UK, Columbia University, Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Ministerio de Ciencia e Innovación (España), National Institute for Health Research (UK), University of Helsinki, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministero dell'Istruzione, dell'Università e della Ricerca, Ministero della Salute, National Health and Medical Research Council (Australia), Instituto Nacional del Cáncer (España), National Cancer Institute (US), Avon Foundation for Women, VU University medical center, Human genetics, CCA - Oncogenesis, Clinical Genetics, Pediatric Surgery, Neurology, Medical Oncology, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human Genetics, CCA -Cancer Center Amsterdam, and ARD - Amsterdam Reproduction and Development
Subjects: Oncology, endocrine system diseases, Epidemiology, Estrogen receptor, Breast Neoplasms - epidemiology - genetics - metabolism, DCN PAC - Perception action and control, Immunoenzyme Techniques, 0302 clinical medicine, Risk Factors, Genotype, skin and connective tissue diseases, Ovarian Neoplasms, 0303 health sciences, Ovarian Neoplasms - epidemiology - genetics - metabolism, BRCA1 Protein, Middle Aged, BRCA2 Protein, Prognosis, 3. Good health, DNA-Binding Proteins, Receptors, Estrogen, Risk factors for breast cancer, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Female, Adult, medicine.medical_specialty, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Breast Neoplasms, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Genetics and epigenetic pathways of disease Translational research [NCMLS 6], 030304 developmental biology, Aged, Chromosomes, Human, Pair 19 - genetics, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Cancer, BRCA1 Protein - genetics, medicine.disease, United States, BRCA2 Protein - genetics, Immunology, Mutation, Ovarian cancer, business, Chromosomes, Human, Pair 19, Genome-Wide Association Study, Transcription Factors
Abstract: PMCID: PMC3319317.-- et al., [Background]: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). [Methods]: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. [Results]: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10(-3)). [Conclusions]: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. [Impact]: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers., This research was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This work was also supported by Cancer Research UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). Support was also provided by the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program and by the Canadian Breast Cancer Research Alliance-grant #019511., A.C. Antoniou is a CR-UK Senior Cancer Research Fellow. D.F. Easton is CR-UK Principal Research Fellow. G. Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was partially supported by Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, the Spanish Ministry of Science and Innovation (FIS PI08 1120), and the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 “Alleanza contro il Cancro” to L. Varesco and P. Radice, and “Progetto Tumori Femminili” to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul Cancro (Special Project “Hereditary tumors” to P. Radice), Associazione Italiana per la Ricerca sul Cancro (4017 to P. Pujol), and by funds from Italian citizens who allocated the 5 × 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”)., The DKFZ study was supported by funds from the DKFZ. EMBRACE was supported by CR-UK Grants C1287/A10118 and C1287/A11990. D.G. Evans and Fiona Lalloo were supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R.A. Eeles, Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC). The GEMO study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association “Le cancer du sein, parlons-en!” Award. The Georgetown study was supported by the Familial Cancer Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program—COPTRG) NCI programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical Research Fellow. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the Hungarian Research Grant KTIA-OTKA CK-80745. ICO was supported by Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was supported by a Polish Foundation of Science award to K. Jaworska, a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. ILUH was supported by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund., INHERIT was supported with J. Simard, Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR), and “Ministero della Salute” (“Progetto Tumori Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9”). kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC [145684, 288704, 454508]. A.-B. Skytte is supported by a NHMRC Senior Research Fellowship. A.K. Godwin was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. The McGill study was supported by the Jewish General Hospital Weekend to End Breast Cancer. M. Thomassen holds a Fonds de la Recherche en Santé du Québec clinician-scientist award. The MSKCC study was supported by the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative. The NCI study was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. NNPIO was supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency for Science and Innovations (contract 16.512.11.2237)., OCGN was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. OSU-CCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano Tumori grant to M.A. Caligo. SEABASS was supported by CARIF and University Malaya. The UCSF study was supported by the Helen Diller Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a project grant from CRUK to P.P.D. Pharoah. The UPENN study was supported Komen Foundation for the Cure to S.M. Domchek, the Breast Cancer Research Foundation to K.L. Nathanson, and NIH grants R01-CA083855 and R01-CA102776 to T.R. Rebbeck. WCRI was supported by the American Cancer Society Clinical Research Professorship #SIOP-06-258-06-COUN.
Published: 2012

29. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Author: Antoniou, A.C., Wang, X.S., Fredericksen, Z.S., McGuffog, L., Tarrell, R., Sinilnikova, O.M., Healey, S., Morrison, J., Kartsonaki, C., Lesnick, T., Ghoussaini, M., Barrowdale, D., Peock, S., Cook, M., Oliver, C., Frost, D., Eccles, D., Evans, D.G., Eeles, R., Izatt, L., Chu, C., Douglas, F., Paterson, J., Stoppa-Lyonnet, D., Houdayer, C., Mazoyer, S., Giraud, S., Lasset, C., Remenieras, A., Caron, O., Hardouin, A., Berthet, P., Hogervorst, F.B.L., Rookus, M.A., Jager, A., Ouweland, A. van den, Hoogerbrugge, N., Luijt, R.B. van der, Meijers-Heijboer, H., Garcia, E.B.G., Devilee, P., Vreeswijk, M.P.G., Lubinski, J., Jakubowska, A., Gronwald, J., Huzarski, T., Byrski, T., Gorski, B., Cybulski, C., Spurdle, A.B., Holland, H., Goldgar, D.E., John, E.M., Hopper, J.L., Southey, M., Buys, S.S., Daly, M.B., Terry, M.B., Schmutzler, R.K., Wappenschmidt, B., Engel, C., Meindl, A., Preisler-Adams, S., Arnold, N., Niederacher, D., Sutter, C., Domchek, S.M., Nathanson, K.L., Rebbeck, T., Blum, J.L., Piedmonte, M., Rodriguez, G.C., Wakeley, K., Boggess, J.F., Basil, J., Blank, S.V., Friedman, E., Kaufman, B., Laitman, Y., Milgrom, R., Andrulis, I.L., Glendon, G., Ozcelik, H., Kirchhoff, T., Vijai, J., Gaudet, M.M., Altshuler, D., Guiducci, C., Loman, N., Harbst, K., Rantala, J., Ehrencrona, H., Gerdes, A.M., Thomassen, M., Sunde, L., Peterlongo, P., Manoukian, S., Bonanni, B., Viel, A., Radice, P., Caldes, T., Hoya, M. de la, Singer, C.F., Fink-Retter, A., Greene, M.H., Mai, P.L., Loud, J.T., Guidugli, L., Lindor, N.M., Hansen, T.V.O., Nielsen, F.C., Blanco, I., Lazaro, C., Garber, J., Ramus, S.J., Gayther, S.A., Phelan, C., Narod, S., Szabo, C.I., Benitez, J., Osorio, A., Nevanlinna, H., Heikkinen, T., Caligo, M.A., Beattie, M.S., Hamann, U., Godwin, A.K., Montagna, M., Casella, C., Neuhausen, S.L., Karlan, B.Y., Tung, N., Toland, A.E., Weitzel, J., Olopade, O., Simard, J., Soucy, P., Rubinstein, W.S., Arason, A., Rennert, G., Martin, N.G., Montgomery, G.W., Chang-Claude, J., Flesch-Janys, D., Brauch, H., Severi, G., Baglietto, L., Cox, A., Cross, S.S., Miron, P., Gerty, S.M., Tapper, W., Yannoukakos, D., Fountzilas, G., Fasching, P.A., Beckmann, M.W., Silva, I.D.S., Peto, J., Lambrechts, D., Paridaens, R., Rudiger, T., Forsti, A., Winqvist, R., Pylkaas, K., Diasio, R.B., Lee, A.M., Eckel-Passow, J., Vachon, C., Blows, F., Driver, K., Dunning, A., Pharoah, P.P.D., Offit, K., Pankratz, V.S., Hakonarson, H., Chenevix-Trench, G., Easton, D.F., Couch, F.J., EMBRACE, GEMO Study Collaborators, HEBON, KConFab, SWE-BRCA, MOD SQUAD, GENICA, Human genetics, CCA - Oncogenesis, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Human Genetics, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Medical Oncology, Clinical Genetics, and Internal Medicine
Subjects: Oncology, Genetics and epigenetic pathways of disease [NCMLS 6], Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Estrogen receptor, Gene mutation, 0302 clinical medicine, ErbB-2, Adult, BRCA1 Protein, Breast Neoplasms, Case-Control Studies, Chromosomes, Human, Pair 19, Female, Genotype, Humans, Mutation, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, Genetic Predisposition to Disease, Genetics, Receptors, Progesterone, 0303 health sciences, education.field_of_study, Single Nucleotide, 3. Good health, 030220 oncology & carcinogenesis, Breast disease, Human, Receptor, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Receptor, erbB-2, Population, Biology, Article, Chromosomes, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, genome-wide association estrogen-receptor common variants confer susceptibility ovarian-cancer nonsense alleles complex 2q35, Polymorphism, education, 030304 developmental biology, Hereditary cancer and cancer-related syndromes [ONCOL 1], Pair 19, Case-control study, Cancer, Odds ratio, medicine.disease, Estrogen, Endocrinology
Abstract: International audience; Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
Published: 2010

30. Expression of oncofetal RNA-binding protein CRD-BP/IMP1 predicts clinical outcome in colon cancer

Author: Dimitriadis, E. Trangas, T. Milatos, S. Foukas, P.G. Gioulbasanis, I. Courtis, N. Nielsen, F.C. Pandis, N. Dafni, U. Bardi, G. Ioannidis, P.
Subjects: eye diseases
Abstract: The oncofetal CRD-BP/IMP1 RNA binding protein regulates post-transcriptionally a handful of RNA transcripts, implicated in cell adhesion and invadopodia formation and was recently identified as a target of the β-catenin/Tcf transcription factor that is constitutively activated in colorectal carcinomas (CRCs). The expression of CRD-BP/IMP1 was studied in normal adult intestines and CRCs. In normal mucosa, CRD-BP/IMP1 immunoreactivity was observed in few scattered cells located predominantly at or near the bottom of the crypts, whereas in CRCs the protein was detectable in tumor cells of 50% of the specimens analyzed. CRD-BP/ IMP1 mRNA expression was measured by qRT-PCR in 78 CRCs. Thirty-two (41%) of the specimens were negative or had negligible expression, whereas the remaining forty-six (59%) expressed a wide range of CRD-BP/IMP1 mRNA levels. CRD-BP/IMP1 mRNA expression correlated with that of the putative stem/progenitor cell marker Musashi-1 mRNA (p = 0. 035). CRD-BP/IMP1 positive tumors metastasized and/or recurred more frequently (p = 0.001) and its expression defined a group of patients with shorter survival (p = 0.014). Furthermore, in a multivariate analysis CRD-BP/IMP1 expression was found to be an independent predictor of survival (p = 0.015). For stage I & II patients, the differences in metastasis/recurrence and survival rates remained significant (p = 0.001 and 0.033, respectively). These findings indicate that CRD-BP/IMP1 positive tumors exhibit early disease dissemination and unfavorable prognosis. © 2007 Wiley-Liss, Inc.
Published: 2007

31. Cushing's disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1

Author: Rix, M., Hertel, N.T., Nielsen, F.C., Jacobsen, B.B., Højberg, A.S., Brixen, K., Hangaard, J., and Kroustrup, J.P.
Published: 2004

32. Cushing's disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1 (MEN1)

Author: Rix, M., Hertel, N.T., Nielsen, F.C., Jacobsen, B.B., Hoejberg, A.S., and Brixen, Kim
Published: 2004

33. Unexpectedly high, but still asymatomatic iron overload in a patient with pyruvate kinase deficiency

Author: Andersen, F.D, d'Amore, Francesco Annibale, Nielsen, F.C, van Solinge, W, Jensen, F, and Jensen, Peter-Diedrich
Published: 2004

34. SY2-1: Insulin-like growth factor 2 mRNA binding proteins (IMP/IGF2BP) as mRNA safe houses in cancer and development

Author: Christiansen, J., primary, Jønson, L., additional, Vikesaa, J., additional, Hansen, T.v.O., additional, and Nielsen, F.C., additional
Published: 2014
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35. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk.

Author: Couch, F.J., Wang, X., McGuffog, L., Lee, A., Olswold, C., Kuchenbaecker, K.B., Soucy, P., Fredericksen, Z., Barrowdale, D., Dennis, J., Gaudet, M.M., Dicks, E., Kosel, M., Healey, S., Sinilnikova, O.M., Bacot, F., Vincent, D., Hogervorst, F.B., Peock, S., Stoppa-Lyonnet, D., Jakubowska, A., Radice, P., Schmutzler, R.K., Domchek, S.M., Piedmonte, M., Singer, C.F., Friedman, E., Thomassen, M., Hansen, T.V., Neuhausen, S.L., Szabo, C.I., Blanco, I., Greene, M.H., Karlan, B.Y., Garber, J., Phelan, C.M., Weitzel, J.N., Montagna, M., Olah, E., Andrulis, I.L., Godwin, A.K., Yannoukakos, D., Goldgar, D.E., Caldes, T., Nevanlinna, H., Osorio, A., Terry, M.B., Daly, M.B., Rensburg, E.J. van, Hamann, U., Ramus, S.J., Ewart Toland, A., Caligo, M.A., Olopade, O.I., Tung, N., Claes, K., Beattie, M.S., Southey, M.C., Imyanitov, E.N., Tischkowitz, M., Janavicius, R., John, E.M., Kwong, A., Diez, O., Balmana, J., Barkardottir, R.B., Arun, B.K., Rennert, G., Teo, S.H., Ganz, P.A., Campbell, I., Hout, A.H. van der, Deurzen, C.H. van, Seynaeve, C., Gomez Garcia, E.B., Leeuwen, F.E. van, Meijers-Heijboer, H.E., Gille, J.J.P., Ausems, M.G., Blok, M.J., Ligtenberg, M.J.L., Rookus, M.A., Devilee, P., Verhoef, S., Os, T.A. van, Wijnen, J.T., Frost, D., Ellis, S., Fineberg, E., Platte, R., Evans, D.G., Izatt, L., Eeles, R.A., Adlard, J., Eccles, D.M., Cook, J., Brewer, C., Douglas, F., Hodgson, S., Morrison, P.J., Side, L.E., Donaldson, A., Houghton, C., Rogers, M.T., Dorkins, H., Eason, J., Gregory, H., McCann, E., Murray, A., Calender, A., Hardouin, A., Berthet, P., Delnatte, C., Nogues, C., Lasset, C., Houdayer, C., Leroux, D., Rouleau, E., Prieur, F., Damiola, F., Sobol, H., Coupier, I., Venat-Bouvet, L., Castera, L., Gauthier-Villars, M., Leone, M., Pujol, P., Mazoyer, S., Bignon, Y.J., Zlowocka-Perlowska, E., Gronwald, J., Lubinski, J., Durda, K., Jaworska, K., Huzarski, T., Spurdle, A.B., Viel, A., Peissel, B., Bonanni, B., Melloni, G., Ottini, L., Papi, L., Varesco, L., Tibiletti, M.G., Peterlongo, P., Volorio, S., Manoukian, S., Pensotti, V., Arnold, N., Engel, C., Deissler, H., Gadzicki, D., Gehrig, A., Kast, K., Rhiem, K., Meindl, A., Niederacher, D., Ditsch, N., Plendl, H., Preisler-Adams, S., Engert, S., Sutter, C., Varon-Mateeva, R., Wappenschmidt, B., Weber, B.H., Arver, B., Stenmark-Askmalm, M., Loman, N., Rosenquist, R., Einbeigi, Z., Nathanson, K.L., Rebbeck, T.R., Blank, S.V., Cohn, D.E., Rodriguez, G.C., Small, L., Friedlander, M., Bae-Jump, V.L., Fink-Retter, A., Rappaport, C., Gschwantler-Kaulich, D., Pfeiler, G., Tea, M.K., Lindor, N.M., Kaufman, B., Shimon Paluch, S., Laitman, Y., Skytte, A.B., Gerdes, A.M., Pedersen, I.S., Moeller, S.T., Kruse, T.A., Jensen, U.B., Vijai, J., Sarrel, K., Robson, M., Kauff, N., Mulligan, A.M., Glendon, G., Ozcelik, H., Ejlertsen, B., Nielsen, F.C., Jonson, L., Andersen, M.K., Ding, Y.C., Steele, L., Foretova, L., Teule, A., Lazaro, C., Brunet, J., Pujana, M.A., Mai, P.L., Loud, J.T., Walsh, C., Lester, J., Orsulic, S., Narod, S.A., Herzog, J., Sand, S.R., Tognazzo, S., Agata, S., Vaszko, T., Weaver, J., Stavropoulou, A.V., Buys, S.S., Romero, A., Hoya, M. de la, Aittomaki, K., Muranen, T.A., Duran, M., Chung, W.K., Lasa, A., Dorfling, C.M., Miron, A., Benitez, J., Senter, L., Huo, D., Chan, S.B., Sokolenko, A.P., Chiquette, J., Tihomirova, L., Friebel, T.M., Agnarsson, B.A., Lu, K.H., Lejbkowicz, F., James, P.A., Hall, P., Dunning, A.M., Tessier, D., Cunningham, J., Slager, S.L., Wang, C., Hart, S., Stevens, K., Simard, J., Pastinen, T., Pankratz, V.S., Offit, K., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., et al., Couch, F.J., Wang, X., McGuffog, L., Lee, A., Olswold, C., Kuchenbaecker, K.B., Soucy, P., Fredericksen, Z., Barrowdale, D., Dennis, J., Gaudet, M.M., Dicks, E., Kosel, M., Healey, S., Sinilnikova, O.M., Bacot, F., Vincent, D., Hogervorst, F.B., Peock, S., Stoppa-Lyonnet, D., Jakubowska, A., Radice, P., Schmutzler, R.K., Domchek, S.M., Piedmonte, M., Singer, C.F., Friedman, E., Thomassen, M., Hansen, T.V., Neuhausen, S.L., Szabo, C.I., Blanco, I., Greene, M.H., Karlan, B.Y., Garber, J., Phelan, C.M., Weitzel, J.N., Montagna, M., Olah, E., Andrulis, I.L., Godwin, A.K., Yannoukakos, D., Goldgar, D.E., Caldes, T., Nevanlinna, H., Osorio, A., Terry, M.B., Daly, M.B., Rensburg, E.J. van, Hamann, U., Ramus, S.J., Ewart Toland, A., Caligo, M.A., Olopade, O.I., Tung, N., Claes, K., Beattie, M.S., Southey, M.C., Imyanitov, E.N., Tischkowitz, M., Janavicius, R., John, E.M., Kwong, A., Diez, O., Balmana, J., Barkardottir, R.B., Arun, B.K., Rennert, G., Teo, S.H., Ganz, P.A., Campbell, I., Hout, A.H. van der, Deurzen, C.H. van, Seynaeve, C., Gomez Garcia, E.B., Leeuwen, F.E. van, Meijers-Heijboer, H.E., Gille, J.J.P., Ausems, M.G., Blok, M.J., Ligtenberg, M.J.L., Rookus, M.A., Devilee, P., Verhoef, S., Os, T.A. van, Wijnen, J.T., Frost, D., Ellis, S., Fineberg, E., Platte, R., Evans, D.G., Izatt, L., Eeles, R.A., Adlard, J., Eccles, D.M., Cook, J., Brewer, C., Douglas, F., Hodgson, S., Morrison, P.J., Side, L.E., Donaldson, A., Houghton, C., Rogers, M.T., Dorkins, H., Eason, J., Gregory, H., McCann, E., Murray, A., Calender, A., Hardouin, A., Berthet, P., Delnatte, C., Nogues, C., Lasset, C., Houdayer, C., Leroux, D., Rouleau, E., Prieur, F., Damiola, F., Sobol, H., Coupier, I., Venat-Bouvet, L., Castera, L., Gauthier-Villars, M., Leone, M., Pujol, P., Mazoyer, S., Bignon, Y.J., Zlowocka-Perlowska, E., Gronwald, J., Lubinski, J., Durda, K., Jaworska, K., Huzarski, T., Spurdle, A.B., Viel, A., Peissel, B., Bonanni, B., Melloni, G., Ottini, L., Papi, L., Varesco, L., Tibiletti, M.G., Peterlongo, P., Volorio, S., Manoukian, S., Pensotti, V., Arnold, N., Engel, C., Deissler, H., Gadzicki, D., Gehrig, A., Kast, K., Rhiem, K., Meindl, A., Niederacher, D., Ditsch, N., Plendl, H., Preisler-Adams, S., Engert, S., Sutter, C., Varon-Mateeva, R., Wappenschmidt, B., Weber, B.H., Arver, B., Stenmark-Askmalm, M., Loman, N., Rosenquist, R., Einbeigi, Z., Nathanson, K.L., Rebbeck, T.R., Blank, S.V., Cohn, D.E., Rodriguez, G.C., Small, L., Friedlander, M., Bae-Jump, V.L., Fink-Retter, A., Rappaport, C., Gschwantler-Kaulich, D., Pfeiler, G., Tea, M.K., Lindor, N.M., Kaufman, B., Shimon Paluch, S., Laitman, Y., Skytte, A.B., Gerdes, A.M., Pedersen, I.S., Moeller, S.T., Kruse, T.A., Jensen, U.B., Vijai, J., Sarrel, K., Robson, M., Kauff, N., Mulligan, A.M., Glendon, G., Ozcelik, H., Ejlertsen, B., Nielsen, F.C., Jonson, L., Andersen, M.K., Ding, Y.C., Steele, L., Foretova, L., Teule, A., Lazaro, C., Brunet, J., Pujana, M.A., Mai, P.L., Loud, J.T., Walsh, C., Lester, J., Orsulic, S., Narod, S.A., Herzog, J., Sand, S.R., Tognazzo, S., Agata, S., Vaszko, T., Weaver, J., Stavropoulou, A.V., Buys, S.S., Romero, A., Hoya, M. de la, Aittomaki, K., Muranen, T.A., Duran, M., Chung, W.K., Lasa, A., Dorfling, C.M., Miron, A., Benitez, J., Senter, L., Huo, D., Chan, S.B., Sokolenko, A.P., Chiquette, J., Tihomirova, L., Friebel, T.M., Agnarsson, B.A., Lu, K.H., Lejbkowicz, F., James, P.A., Hall, P., Dunning, A.M., Tessier, D., Cunningham, J., Slager, S.L., Wang, C., Hart, S., Stevens, K., Simard, J., Pastinen, T., Pankratz, V.S., Offit, K., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., and et al.
Abstract: 01 maart 2013, Contains fulltext : 115394.pdf (publisher's version ) (Open Access), BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7x10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4x10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4x10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2x10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
Published: 2013

36. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), Dite, G.S. (Gillian), Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), and Dite, G.S. (Gillian)
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associati
Published: 2013
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37. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Author: Antoniou, A.C., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Lee, A., Barrowdale, D., Healey, S., Sinilnikova, O.M., Caligo, M.A., Loman, N., Harbst, K., Lindblom, A., Arver, B., Rosenquist, R., Karlsson, P., Nathanson, K., Domchek, S., Rebbeck, T., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowowcka-Perlowska, E., Osorio, A., Duran, M., Andres, R., Benitez, J., Hamann, U., Hogervorst, F.B., van Os, T.A., Verhoef, S., Meijers-Heijboer, H.E., Wijnen, J., Gomez Garcia, E.B., Ligtenberg, M.J.L., Kriege, M., Collee, J.M., Ausems, M.G., Oosterwijk, J.C., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Jacobs, C, Eeles, R., Adlard, J., Davidson, R., Cole, T., Cook, J.L., Paterson, J., Douglas, F., Brewer, C., Hodgson, S., Morrison, P.J., Walker, L., Rogers, M.T., Donaldson, A., Dorkins, H., Godwin, A.K., Bove, B., Stoppa-Lyonnet, D., Houdayer, C., Buecher, B., de Pauw, A., Mazoyer, S., Calender, A., Leone, M., Bressac-de Paillerets, B., Caron, O., Sobol, H., Frenay, M., Prieur, F., Ferrer, S.U., Mortemousque, I., Buys, S., Daly, M., Miron, A., Terry, M.U., Hopper, J.L., John, E.M., Southey, M., Goldgar, D., Singer, C.F., Fink-Retter, A., Tea, M.K., Kaulich, D.U., Hansen, T.V., Nielsen, F.C., Barkardottir, R.B., Gaudet, M., Kirchhoff, T., Joseph, V., Dutra-Clarke, A., Offit, K., Piedmonte, M., et al., Antoniou, A.C., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Lee, A., Barrowdale, D., Healey, S., Sinilnikova, O.M., Caligo, M.A., Loman, N., Harbst, K., Lindblom, A., Arver, B., Rosenquist, R., Karlsson, P., Nathanson, K., Domchek, S., Rebbeck, T., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowowcka-Perlowska, E., Osorio, A., Duran, M., Andres, R., Benitez, J., Hamann, U., Hogervorst, F.B., van Os, T.A., Verhoef, S., Meijers-Heijboer, H.E., Wijnen, J., Gomez Garcia, E.B., Ligtenberg, M.J.L., Kriege, M., Collee, J.M., Ausems, M.G., Oosterwijk, J.C., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Jacobs, C, Eeles, R., Adlard, J., Davidson, R., Cole, T., Cook, J.L., Paterson, J., Douglas, F., Brewer, C., Hodgson, S., Morrison, P.J., Walker, L., Rogers, M.T., Donaldson, A., Dorkins, H., Godwin, A.K., Bove, B., Stoppa-Lyonnet, D., Houdayer, C., Buecher, B., de Pauw, A., Mazoyer, S., Calender, A., Leone, M., Bressac-de Paillerets, B., Caron, O., Sobol, H., Frenay, M., Prieur, F., Ferrer, S.U., Mortemousque, I., Buys, S., Daly, M., Miron, A., Terry, M.U., Hopper, J.L., John, E.M., Southey, M., Goldgar, D., Singer, C.F., Fink-Retter, A., Tea, M.K., Kaulich, D.U., Hansen, T.V., Nielsen, F.C., Barkardottir, R.B., Gaudet, M., Kirchhoff, T., Joseph, V., Dutra-Clarke, A., Offit, K., and Piedmonte, M., et al.
Abstract: Contains fulltext : 110606.pdf (publisher's version ) (Open Access), INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). METHODS: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. RESULTS: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). CONCLUSIONS: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
Published: 2012

38. Characterization of MYG1 gene and protein: Subcellular distribution and function

Author: Philips, M-A, Vikeså, J., Luuk, H., Jønson, L., Lilleväli, K., Rehfeld, J.F., Vasar, E., Kõks, S., Nielsen, F.C., Philips, M-A, Vikeså, J., Luuk, H., Jønson, L., Lilleväli, K., Rehfeld, J.F., Vasar, E., Kõks, S., and Nielsen, F.C.
Abstract: Background information. MYG1 [Melanocyte proliferating gene 1, also known as Gamm1 (NM_021640)] is a recently described gene of unknown function. MYG1 orthologues are found in simple as well as complex eukaryotes. According to sequence homology, MYG1 is considered to have a metal‐dependent protein hydrolase (UPF0160) domain. The purpose of the present study was to determine the expression and subcellular localization of MYG1 protein and to identify physiological processes connected to MYG1 function. Results. Human and mouse MYG1 is ubiquitously expressed, with the highest level in the testis. Analysis of mouse embryos moreover revealed a uniform Myg1 expression at E (embryonic day) 8.5, but at E11.75 expression becomes restricted predominantly to the developing brain and eye, limb buds and tail region. MYG1 exhibits a mitochondrial targeting signal in the N‐terminal region and a Pat7‐type nuclear localization signal in the region between amino acids 33–39 and localizes to these compartments. No active shuttling of MYG1 between the nucleus and the mitochondria was detected and the distribution of MYG1 was not dependent on the phase of the cell cycle. Immunoprecipitation of C‐terminally FLAG‐tagged MYG1 from HeLa cells did not identify any co‐precipitated proteins. siRNA (short interfering RNA)‐mediated knockdown of MYG1 mRNA was mainly followed by changes in the level of transcripts encoding factors involved in developmental tissue patterning and growth as well as immune‐related processes. Conclusions. Taken together, we infer that MYG1 is a ubiquitous nucleo‐mitochondrial protein, with differential pattern and level of expression during embryonic development. MYG1 expression in normal adult tissues is stable and our data suggest MYG1 involvement in early developmental processes and also in adult stress/illness conditions.
Published: 2012

39. Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

Author: Couch, F.J. (Fergus), Gaudet, M.M. (Mia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Wang, X. (Xing), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Healey, S. (Sue), Sinilnikova, O. (Olga), Andrulis, I.L. (Irene), Ozcelik, H. (Hilmi), Mulligan, A.M. (Anna Marie), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Kruse, T.A. (Torben), Caligo, M.A. (Maria), Wachenfeldt, A. (Anna) von, Barbany-Bustinza, G. (Gisela), Loman, N. (Niklas), Soller, M. (Maria), Ehrencrona, H. (Hans), Karlsson, P. (Per), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Zołwocka, E. (Elzbieta), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.I., Benítez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Os, T.A.M. (Theo) van, Leeuwen, F. (Fred) van, Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Blok, M.J. (Marinus), Kets, C.M. (Marleen), Hooning, M.J. (Maartje), Oldenburg, R.A. (Rogier), Ausems, M.G.E.M. (Margreet), Peock, S. (Susan), Frost, D. (Debra), Ellis, S.D. (Steve), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Jacobs, C. (Chris), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T.J. (Trevor), Cook, J. (Jackie), Paterson, J. (Joan), Brewer, C. (Carole), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Side, L. (Lucy), Bove, B. (B.), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Fassy-Colcombet, M. (Marion), Castera, L. (Laurent), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Pujol, P. (Pascal), Coupier, I. (Isabelle), Delnatte, C.D. (Capucine), Akloul, L. (Linda), Lynch, H. (Henry), Snyder, C.L. (Carrie), Buys, S.S. (Saundra), Daly, M.B. (Mary), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Hopper, J.L. (John), Goldgar, D. (David), Singer, C.F. (Christian), Rappaport, C. (Christine), Tea, M.-K., Fink-Retter, A. (Anneliese), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Arason, A. (Adalgeir), Vijai, J. (Joseph), Shah, S. (Sonia), Sarrel, K. (Kara), Robson, M. (Mark), Piedmonte, M. (Marion), Phillips, K. (Kelly), Basil, J. (Jack), Rubinstein, W.S. (Wendy), Boggess, J.F. (John), Wakeley, K. (Katie), Ewart-Toland, A. (Amanda), Montagna, M. (Marco), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Feliubadaló, L. (L.), Brunet, J. (Joan), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Odunsi, K. (Kunle), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E., Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Dorfling, C.M. (Cecelia), Diez, O. (Orland), Kwong, A. (Ava), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Heidemann, S. (Simone), Niederacher, D. (Dieter), Preisler-Adams, S. (Sabine), Gadzicki, D. (Dorothea), Varon-Mateeva, R. (Raymonda), Deissler, H. (Helmut), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Kast, K. (Karin), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Muranen, T.A. (Taru), Nevanlinna, H. (Heli), Tischkowitz, M. (Marc), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Lindor, N.M. (Noralane), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Bernard, L. (Loris), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Varesco, L. (Liliana), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Simard, J. (Jacques), Couch, F.J. (Fergus), Gaudet, M.M. (Mia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Wang, X. (Xing), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Healey, S. (Sue), Sinilnikova, O. (Olga), Andrulis, I.L. (Irene), Ozcelik, H. (Hilmi), Mulligan, A.M. (Anna Marie), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Kruse, T.A. (Torben), Caligo, M.A. (Maria), Wachenfeldt, A. (Anna) von, Barbany-Bustinza, G. (Gisela), Loman, N. (Niklas), Soller, M. (Maria), Ehrencrona, H. (Hans), Karlsson, P. (Per), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Zołwocka, E. (Elzbieta), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.I., Benítez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Os, T.A.M. (Theo) van, Leeuwen, F. (Fred) van, Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Blok, M.J. (Marinus), Kets, C.M. (Marleen), Hooning, M.J. (Maartje), Oldenburg, R.A. (Rogier), Ausems, M.G.E.M. (Margreet), Peock, S. (Susan), Frost, D. (Debra), Ellis, S.D. (Steve), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Jacobs, C. (Chris), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T.J. (Trevor), Cook, J. (Jackie), Paterson, J. (Joan), Brewer, C. (Carole), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Side, L. (Lucy), Bove, B. (B.), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Fassy-Colcombet, M. (Marion), Castera, L. (Laurent), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Pujol, P. (Pascal), Coupier, I. (Isabelle), Delnatte, C.D. (Capucine), Akloul, L. (Linda), Lynch, H. (Henry), Snyder, C.L. (Carrie), Buys, S.S. (Saundra), Daly, M.B. (Mary), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Hopper, J.L. (John), Goldgar, D. (David), Singer, C.F. (Christian), Rappaport, C. (Christine), Tea, M.-K., Fink-Retter, A. (Anneliese), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Arason, A. (Adalgeir), Vijai, J. (Joseph), Shah, S. (Sonia), Sarrel, K. (Kara), Robson, M. (Mark), Piedmonte, M. (Marion), Phillips, K. (Kelly), Basil, J. (Jack), Rubinstein, W.S. (Wendy), Boggess, J.F. (John), Wakeley, K. (Katie), Ewart-Toland, A. (Amanda), Montagna, M. (Marco), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Feliubadaló, L. (L.), Brunet, J. (Joan), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Odunsi, K. (Kunle), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E., Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Dorfling, C.M. (Cecelia), Diez, O. (Orland), Kwong, A. (Ava), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Heidemann, S. (Simone), Niederacher, D. (Dieter), Preisler-Adams, S. (Sabine), Gadzicki, D. (Dorothea), Varon-Mateeva, R. (Raymonda), Deissler, H. (Helmut), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Kast, K. (Karin), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Muranen, T.A. (Taru), Nevanlinna, H. (Heli), Tischkowitz, M. (Marc), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Lindor, N.M. (Noralane), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Bernard, L. (Loris), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Varesco, L. (Liliana), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), and Simard, J. (Jacques)
Abstract: Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10 -4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers.Wealso found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10 -4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10-3). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers.
Published: 2012
Full Text: View/download PDF

40. Is thyreoidectomy necessary in RET mutations carries of the familial medullary thyroid carcinoma syndrome?

Author: Hansen, Hanne Sand, Torring, H., C., Godballe, Jager, A.C., and Nielsen, F.C.
Published: 2000

41. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Author: Mulligan, A.M., Couch, F.J., Barrowdale, D., Domchek, S.M., Eccles, D., Nevanlinna, H., Ramus, S.J., Robson, M., Sherman, M., Spurdle, A.B., Wappenschmidt, B., Lee, A., McGuffog, L., Healey, S., Sinilnikova, O.M., Janavicius, R., Hansen, T.V., Nielsen, F.C., Ejlertsen, B., Osorio, A., Munoz-Repeto, I., Duran, M., Godino, J., Pertesi, M., Benitez, J., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Bonanni, B., Viel, A., Pasini, B., Papi, L., Ottini, L., Savarese, A., Bernard, L., Radice, P., Hamann, U., Verheus, M., Meijers-Heijboer, H.E., Wijnen, J., Gomez Garcia, E.B., Nelen, M.R., Kets, C.M., Seynaeve, C., Tilanus-Linthorst, M.M., Luijt, R.B. van der, Os, T.V., Rookus, M., Frost, D., Jones, J.L., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Cook, J., Donaldson, A., Dorkins, H., Gregory, H., Eason, J., Houghton, C., Barwell, J., Side, L.E., McCann, E., Murray, A., Peock, S., Godwin, A.K., Schmutzler, R.K., Rhiem, K., Engel, C., Meindl, A., Ruehl, I., Arnold, N., Niederacher, D., Sutter, C., Deissler, H., Gadzicki, D., Kast, K., Preisler-Adams, S., Varon-Mateeva, R., Schoenbuchner, I., Fiebig, B., Heinritz, W., Schafer, D., Gevensleben, H., Caux-Moncoutier, V., Fassy-Colcombet, M., Cornelis, F., Mazoyer, S., Leone, M., Boutry-Kryza, N., Hardouin, A., Berthet, P., Muller, D., Fricker, J.P., Mortemousque, I., Pujol, P., et al., Mulligan, A.M., Couch, F.J., Barrowdale, D., Domchek, S.M., Eccles, D., Nevanlinna, H., Ramus, S.J., Robson, M., Sherman, M., Spurdle, A.B., Wappenschmidt, B., Lee, A., McGuffog, L., Healey, S., Sinilnikova, O.M., Janavicius, R., Hansen, T.V., Nielsen, F.C., Ejlertsen, B., Osorio, A., Munoz-Repeto, I., Duran, M., Godino, J., Pertesi, M., Benitez, J., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Bonanni, B., Viel, A., Pasini, B., Papi, L., Ottini, L., Savarese, A., Bernard, L., Radice, P., Hamann, U., Verheus, M., Meijers-Heijboer, H.E., Wijnen, J., Gomez Garcia, E.B., Nelen, M.R., Kets, C.M., Seynaeve, C., Tilanus-Linthorst, M.M., Luijt, R.B. van der, Os, T.V., Rookus, M., Frost, D., Jones, J.L., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Cook, J., Donaldson, A., Dorkins, H., Gregory, H., Eason, J., Houghton, C., Barwell, J., Side, L.E., McCann, E., Murray, A., Peock, S., Godwin, A.K., Schmutzler, R.K., Rhiem, K., Engel, C., Meindl, A., Ruehl, I., Arnold, N., Niederacher, D., Sutter, C., Deissler, H., Gadzicki, D., Kast, K., Preisler-Adams, S., Varon-Mateeva, R., Schoenbuchner, I., Fiebig, B., Heinritz, W., Schafer, D., Gevensleben, H., Caux-Moncoutier, V., Fassy-Colcombet, M., Cornelis, F., Mazoyer, S., Leone, M., Boutry-Kryza, N., Hardouin, A., Berthet, P., Muller, D., Fricker, J.P., Mortemousque, I., Pujol, P., and et al.
Abstract: Contains fulltext : 97737.pdf (publisher's version ) (Open Access), INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 x 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. CONCLUSIONS: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific
Published: 2011

42. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Author: Mulligan, A.M. (Anna Marie), Couch, F.J. (Fergus), Barrowdale, D. (Daniel), Domchek, S.M. (Susan), Eccles, D. (Diana), Nevanlinna, H. (Heli), Ramus, S.J. (Susan), Robson, M. (Mark), Sherman, M.E. (Mark), Spurdle, A.B. (Amanda), Wapenschmidt, B. (Barbara), Lee, A. (Andrew), McGuffog, L. (Lesley), Healey, S. (Sue), Sinilnikova, O. (Olga), Janavicius, R. (Ramunas), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Ejlertsen, B. (Bent), Osorio, A. (Ana), Muñoz-Repeto, I. (Iván), Durán, M. (Mercedes), Godino, J. (Javier), Pertesi, M. (Maroulio), Benítez, J. (Javier), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Cattaneo, E. (Elisa), Bonnani, B. (Bernardo), Viel, A. (Alessandra), Pasini, B. (Barbara), Papi, L. (Laura), Ottini, L. (Laura), Savarese, A. (Antonella), Bernard, L. (Loris), Radice, P. (Paolo), Hamann, U. (Ute), Verheus, M. (Martijn), Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Nelen, M.R. (Marcel), Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), Tilanus-Linthorst, M.M.A. (Madeleine), Luijt, R.B. (Rob) van der, Os, T.V. (Theo), Rookus, M.A. (Matti), Frost, D. (Debra), Jones, J.L. (J Louise), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Cook, J. (Jackie), Donaldson, A. (Alan), Dorkins, H. (Huw), Gregory, H. (Helen), Eason, J. (Jacqueline), Houghton, C. (Catherine), Barwell, J. (Julian), Side, L. (Lucy), McCann, E. (Emma), Murray, A. (Alexandra), Peock, S. (Susan), Godwin, A.K. (Andrew), Schmutzler, R.K. (Rita), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ruehl, I. (Ina), Arnold, N. (Norbert), Niederacher, D. (Dieter), Sutter, C. (Christian), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Kast, K. (Karin), Preisler-Adams, S. (Sabine), Varon-Mateeva, R. (Raymonda), Schoenbuchner, I. (Ines), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Schäfer, D. (Dieter), Gevensleben, H. (Heidrun), Caux-Moncoutier, V. (Virginie), Fassy-Colcombet, M. (Marion), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Mortemousque, I. (Isabelle), Pujol, P. (Pascal), Coupier, I. (Isabelle), Lebrun, M. (Marine), Kientz, C. (Caroline), Longy, M. (Michel), Sevenet, N. (Nicolas), Stoppa-Lyonnet, D. (Dominique), Isaacs, C. (Claudine), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Heikinen, T. (Tuomas), Aittomäki, K. (Kristiina), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Barkardottir, R.B. (Rosa), Soucy, P. (Penny), Dumont, M. (Martine), Simard, J. (Jacques), Montagna, M. (Marco), Tognazzo, S. (Silvia), D'Andrea, E. (Emma), Fox, S.B. (Stephen), Yan, M. (Max), Rebbeck, R. (Timothy), Olopade, O.I. (Olofunmilayo), Weitzel, J.N. (Jeffrey), Lynch, H. (Henry), Ganz, P.A. (Patricia), Tomlinson, G. (Gail), Wang, X. (Xing), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Lindor, N.M. (Noralane), Szabo, C. (Csilla), Offit, K. (Kenneth), Sakr, R. (Rita), Gaudet, M.M. (Mia), Bhatia, K.P. (Kailash), Kauff, N. (Noah), Singer, C.F. (Christian), Tea, M.-K., Gschwantler-Kaulich, D. (Daphne), Fink-Retter, A. (Anneliese), Mai, P.L. (Phuong), Greene, M.H. (Mark), Imyanitov, E.N. (Evgeny), O'Malley, F.P. (Frances), Ozcelik, H. (Hilmi), Glendon, G. (Gord), Toland, A.E. (Amanda), Gerdes, A-M. (Anne-Marie), Thomassen, M. (Mads), Kruse, T.A. (Torben), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Caligo, M.A. (Maria), Soller, M. (Maria), Henriksson, K. (Karin), Wachenfeldt, A. (Anna) von, Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Karlsson, P. (Per), Ding, Y.C. (Yuan), Neuhausen, S.L. (Susan), Beattie, M.S. (Mary), Pharoah, P.D.P. (Paul), Moysich, K.B. (Kirsten), Nathanson, K.L. (Katherine), Karlan, B.Y. (Beth), Gross, J. (Jenny), John, E.M. (Esther), Daly, M.B. (Mary), Buys, S.S. (Saundra), Southey, M.C. (Melissa), Hopper, J.L. (John), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), Miron, A. (Alexander), Goldgar, D. (David), Chenevix-Trench, G. (Georgia), Easton, D.F. (Douglas), Andrulis, I.L. (Irene), Antoniou, A.C. (Antonis), Mulligan, A.M. (Anna Marie), Couch, F.J. (Fergus), Barrowdale, D. (Daniel), Domchek, S.M. (Susan), Eccles, D. (Diana), Nevanlinna, H. (Heli), Ramus, S.J. (Susan), Robson, M. (Mark), Sherman, M.E. (Mark), Spurdle, A.B. (Amanda), Wapenschmidt, B. (Barbara), Lee, A. (Andrew), McGuffog, L. (Lesley), Healey, S. (Sue), Sinilnikova, O. (Olga), Janavicius, R. (Ramunas), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Ejlertsen, B. (Bent), Osorio, A. (Ana), Muñoz-Repeto, I. (Iván), Durán, M. (Mercedes), Godino, J. (Javier), Pertesi, M. (Maroulio), Benítez, J. (Javier), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Cattaneo, E. (Elisa), Bonnani, B. (Bernardo), Viel, A. (Alessandra), Pasini, B. (Barbara), Papi, L. (Laura), Ottini, L. (Laura), Savarese, A. (Antonella), Bernard, L. (Loris), Radice, P. (Paolo), Hamann, U. (Ute), Verheus, M. (Martijn), Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Nelen, M.R. (Marcel), Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), Tilanus-Linthorst, M.M.A. (Madeleine), Luijt, R.B. (Rob) van der, Os, T.V. (Theo), Rookus, M.A. (Matti), Frost, D. (Debra), Jones, J.L. (J Louise), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Cook, J. (Jackie), Donaldson, A. (Alan), Dorkins, H. (Huw), Gregory, H. (Helen), Eason, J. (Jacqueline), Houghton, C. (Catherine), Barwell, J. (Julian), Side, L. (Lucy), McCann, E. (Emma), Murray, A. (Alexandra), Peock, S. (Susan), Godwin, A.K. (Andrew), Schmutzler, R.K. (Rita), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ruehl, I. (Ina), Arnold, N. (Norbert), Niederacher, D. (Dieter), Sutter, C. (Christian), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Kast, K. (Karin), Preisler-Adams, S. (Sabine), Varon-Mateeva, R. (Raymonda), Schoenbuchner, I. (Ines), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Schäfer, D. (Dieter), Gevensleben, H. (Heidrun), Caux-Moncoutier, V. (Virginie), Fassy-Colcombet, M. (Marion), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Mortemousque, I. (Isabelle), Pujol, P. (Pascal), Coupier, I. (Isabelle), Lebrun, M. (Marine), Kientz, C. (Caroline), Longy, M. (Michel), Sevenet, N. (Nicolas), Stoppa-Lyonnet, D. (Dominique), Isaacs, C. (Claudine), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Heikinen, T. (Tuomas), Aittomäki, K. (Kristiina), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Barkardottir, R.B. (Rosa), Soucy, P. (Penny), Dumont, M. (Martine), Simard, J. (Jacques), Montagna, M. (Marco), Tognazzo, S. (Silvia), D'Andrea, E. (Emma), Fox, S.B. (Stephen), Yan, M. (Max), Rebbeck, R. (Timothy), Olopade, O.I. (Olofunmilayo), Weitzel, J.N. (Jeffrey), Lynch, H. (Henry), Ganz, P.A. (Patricia), Tomlinson, G. (Gail), Wang, X. (Xing), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Lindor, N.M. (Noralane), Szabo, C. (Csilla), Offit, K. (Kenneth), Sakr, R. (Rita), Gaudet, M.M. (Mia), Bhatia, K.P. (Kailash), Kauff, N. (Noah), Singer, C.F. (Christian), Tea, M.-K., Gschwantler-Kaulich, D. (Daphne), Fink-Retter, A. (Anneliese), Mai, P.L. (Phuong), Greene, M.H. (Mark), Imyanitov, E.N. (Evgeny), O'Malley, F.P. (Frances), Ozcelik, H. (Hilmi), Glendon, G. (Gord), Toland, A.E. (Amanda), Gerdes, A-M. (Anne-Marie), Thomassen, M. (Mads), Kruse, T.A. (Torben), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Caligo, M.A. (Maria), Soller, M. (Maria), Henriksson, K. (Karin), Wachenfeldt, A. (Anna) von, Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Karlsson, P. (Per), Ding, Y.C. (Yuan), Neuhausen, S.L. (Susan), Beattie, M.S. (Mary), Pharoah, P.D.P. (Paul), Moysich, K.B. (Kirsten), Nathanson, K.L. (Katherine), Karlan, B.Y. (Beth), Gross, J. (Jenny), John, E.M. (Esther), Daly, M.B. (Mary), Buys, S.S. (Saundra), Southey, M.C. (Melissa), Hopper, J.L. (John), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), Miron, A. (Alexander), Goldgar, D. (David), Chenevix-Trench, G. (Georgia), Easton, D.F. (Douglas), Andrulis, I.L. (Irene), and Antoniou, A.C. (Antonis)
Abstract: Introduction: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.Methods: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.Results: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.Conclusions: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models
Published: 2011
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43. 1581PD - Copenhagen prospective personalized oncology (CoPPO): Genomic profiling to select patients for phase 1 trials

Author: Tuxen, I.V., Yde, C.W., Mau-Sørensen, M., Santoni-Rugiu, E., Lassen, U., and Nielsen, F.C.
Published: 2016
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44. Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

Author: Philips, M-A, Kingo, K., Karelson, M., Rätsep, R., Aunin, E., Reimann, E., Reemann, P., Porosaar, O., Vikeså, J., Nielsen, F.C., Vasar, E., Silm, H., Kõks, S., Philips, M-A, Kingo, K., Karelson, M., Rätsep, R., Aunin, E., Reimann, E., Reemann, P., Porosaar, O., Vikeså, J., Nielsen, F.C., Vasar, E., Silm, H., and Kõks, S.
Abstract: Background MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the MYG1 gene, to investigate their functionality, and to study their association with vitiligo susceptibility. Methods Nine single nucleotide polymorphisms (SNPs) in the MYG1 locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). MYG1 expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture. Results Control subjects with -119G promoter allele (rs1465073) exhibited significantly higher MYG1 mRNA levels than controls with -119C allele (P = 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, P < 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% versus 39.3%, P < 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database. Conclusions Our study demonstrated that both MYG1 promoter polymorphism -119C/G and Arg4Gln polymorphism in the mito
Published: 2010

45. Ancient human genome sequence of an extinct Palaeo-Eskimo

Author: Rasmussen, M., Li, Y., Lindgreen, S., Pedersen, J.S., Albrechtsen, A., Moltke, I., Metspalu, M., Metspalu, E., Kivisild, T., Gupta, R., Bertalan, M., Nielsen, K., Gilbert, M.T.P., Wang, Y., Raghavan, M., Campos, P.F., Kamp, H.M., Wilson, A.S., Gledhill, A., Tridico, S., Bunce, M., Lorenzen, E.D., Binladen, J., Guo, X., Zhao, J., Zhang, X., Zhang, H., Li, Z., Chen, M., Orlando, L., Kristiansen, K., Bak, M., Tommerup, N., Bendixen, C., Pierre, T.L., Grønnow, B., Meldgaard, M., Andreasen, C., Fedorova, S.A., Osipova, L.P., Higham, T.F.G., Ramsey, C.B., Hansen, T.O., Nielsen, F.C., Crawford, M.H., Brunak, S., Sicheritz-Pontén, T., Villems, R., Nielsen, R., Krogh, A., Wang, J., Willerslev, E., Rasmussen, M., Li, Y., Lindgreen, S., Pedersen, J.S., Albrechtsen, A., Moltke, I., Metspalu, M., Metspalu, E., Kivisild, T., Gupta, R., Bertalan, M., Nielsen, K., Gilbert, M.T.P., Wang, Y., Raghavan, M., Campos, P.F., Kamp, H.M., Wilson, A.S., Gledhill, A., Tridico, S., Bunce, M., Lorenzen, E.D., Binladen, J., Guo, X., Zhao, J., Zhang, X., Zhang, H., Li, Z., Chen, M., Orlando, L., Kristiansen, K., Bak, M., Tommerup, N., Bendixen, C., Pierre, T.L., Grønnow, B., Meldgaard, M., Andreasen, C., Fedorova, S.A., Osipova, L.P., Higham, T.F.G., Ramsey, C.B., Hansen, T.O., Nielsen, F.C., Crawford, M.H., Brunak, S., Sicheritz-Pontén, T., Villems, R., Nielsen, R., Krogh, A., Wang, J., and Willerslev, E.
Abstract: We report here the genome sequence of an ancient human. Obtained from 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20Ã-, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
Published: 2010

46. MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling

Author: Glud, M., Klausen, M., Gniadecki, R., Rossing, M., Hastrup, N., Nielsen, F.C., Drzewiecki, K.T., Glud, Martin, Klausen, Mikkel, Gniadecki, Robert, Rossing, Maria, Hastrup, Nina, Nielsen, Finn C, Drzewiecki, Krzysztof T, Glud, M., Klausen, M., Gniadecki, R., Rossing, M., Hastrup, N., Nielsen, F.C., Drzewiecki, K.T., Glud, Martin, Klausen, Mikkel, Gniadecki, Robert, Rossing, Maria, Hastrup, Nina, Nielsen, Finn C, and Drzewiecki, Krzysztof T
Abstract: MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate cellular differentiation, proliferation, and apoptosis. MiRNAs are expressed in a developmentally regulated and tissue-specific manner. Aberrant expression may contribute to pathological processes such as cancer, and miRNA may therefore serve as biomarkers that may be useful in a clinical environment for diagnosis of various diseases. Most miRNA profiling studies have used fresh tissue samples. However, in some types of cancer, including malignant melanoma, fresh material is difficult to obtain from primary tumors, and most surgical specimens are formalin fixed and paraffin embedded (FFPE). To explore whether FFPE material would be suitable for miRNA profiling in melanocytic lesions, we compared miRNA expression patterns in FFPE versus fresh frozen samples, obtained from 15 human melanocytic nevi. Out of microarray data, we identified 84 miRNAs that were expressed in both types of samples and represented an miRNA profile of melanocytic nevi. Our results showed a high correlation in miRNA expression (Spearman r-value of 0.80) between paired FFPE and fresh frozen material. The data were further validated by quantitative RT-PCR. In conclusion, FFPE specimens of melanocytic lesions are suitable as a source for miRNA microarray profiling.
Published: 2009

47. [Pharmacogenetics and tailored drug therapy]

Author: Nielsen, F.C., Borregaard, N., Nielsen, F.C., and Borregaard, N.
Abstract: Pharmacogenetics traditionally designates the study of genetically determined variation in metabolism of drugs and toxins from the environment. The concept of phamacogenetics has been widened to encompass how essential genetic alterations central to the development of diseases may by used to target medical treatment in a patient-tailored way. This paper highlights some of the novel developments in relation to oncology and haematology Udgivelsesdato: 2009/3/2
Published: 2009

48. A common Greenlandic Inuit BRCA1 RING domain founder mutation

Author: Hansen, T.v.O., Ejlertsen, B., Albrechtsen, Anders, Bergsten, E., Bjerregaard, P., Hansen, T., Myrhoj, T., Nielsen, P.B., Timmermans-Wielenga, V., Andersen, M.K., Jonson, L., Nielsen, F.C., Hansen, T.v.O., Ejlertsen, B., Albrechtsen, Anders, Bergsten, E., Bjerregaard, P., Hansen, T., Myrhoj, T., Nielsen, P.B., Timmermans-Wielenga, V., Andersen, M.K., Jonson, L., and Nielsen, F.C.
Abstract: Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1 exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented Udgivelsesdato: 2009/5
Published: 2009

49. IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes

Author: Christiansen, J., Kolte, A.M., Hansen, T.O., Nielsen, F.C., Christiansen, J., Kolte, A.M., Hansen, T.O., and Nielsen, F.C.
Abstract: Recent genome-wide association (GWA) studies of type 2 diabetes (T2D) have implicated IGF2 mRNA-binding protein 2 (IMP2/IGF2BP2) as one of the several factors in the etiology of late onset diabetes. IMP2 belongs to a family of oncofetal mRNA-binding proteins implicated in RNA localization, stability, and translation that are essential for normal embryonic growth and development. This review provides a background to the IMP protein family with an emphasis on human IMP2, followed by a closer look at the GWA studies to evaluate the significance, if any, of the proposed correlation between IMP2 and T2D Udgivelsesdato: 2009/11
Published: 2009

50. Gene expression profiling of liver and skeletal muscle in newborn mice exposed to an in utero low protein diet with or without taurine

Author: Olsen, H.L., Mortensen, Ole Hartvig, Nielsen, Peter E., Nielsen, F.C., Grunnet, N., Quistorff, B., Olsen, H.L., Mortensen, Ole Hartvig, Nielsen, Peter E., Nielsen, F.C., Grunnet, N., and Quistorff, B.
Abstract: Udgivelsesdato: 2008/7/19
Published: 2008

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