TY  - JOUR
A1  - Davis, Lea K.
A1  - Yu, Dongmei
A1  - Keenan, Clare L.
A1  - Gamazon, Eric R.
A1  - Konkashbaev, Anuar I.
A1  - Derks, Eske M.
A1  - Neale, Benjamin M.
A1  - Yang, Jian
A1  - Lee, S. Hong
A1  - Evans, Patrick
A1  - Barr, Cathy L.
A1  - Bellodi, Laura
A1  - Benarroch, Fortu
A1  - Berrio, Gabriel Bedoya
A1  - Bienvenu, Oscar J.
A1  - Bloch, Michael H.
A1  - Blom, Rianne M.
A1  - Bruun, Ruth D.
A1  - Budman, Cathy L.
A1  - Camarena, Beatriz
A1  - Campbell, Desmond
A1  - Cappi, Carolina
A1  - Cardona Silgado, Julio C.
A1  - Cath, Danielle C.
A1  - Cavallini, Maria C.
A1  - Chavira, Denise A.
A1  - Chouinard, Sylvian
A1  - Conti, David V.
A1  - Cook, Edwin H.
A1  - Coric, Vladimir
A1  - Cullen, Bernadette A.
A1  - Deforce, Dieter
A1  - Delorme, Richard
A1  - Dion, Yves
A1  - Edlund, Christopher K.
A1  - Egberts, Karin
A1  - Falkai, Peter
A1  - Fernandez, Thomas V.
A1  - Gallagher, Patience J.
A1  - Garrido, Helena
A1  - Geller, Daniel
A1  - Girard, Simon L.
A1  - Grabe, Hans J.
A1  - Grados, Marco A.
A1  - Greenberg, Benjamin D.
A1  - Gross-Tsur, Varda
A1  - Haddad, Stephen
A1  - Heiman, Gary A.
A1  - Hemmings, Sian M. J.
A1  - Hounie, Ana G.
A1  - Illmann, Cornelia
A1  - Jankovic, Joseph
A1  - Jenike, Micheal A.
A1  - Kennedy, James L.
A1  - King, Robert A.
A1  - Kremeyer, Barbara
A1  - Kurlan, Roger
A1  - Lanzagorta, Nuria
A1  - Leboyer, Marion
A1  - Leckman, James F.
A1  - Lennertz, Leonhard
A1  - Liu, Chunyu
A1  - Lochner, Christine
A1  - Lowe, Thomas L.
A1  - Macciardi, Fabio
A1  - McCracken, James T.
A1  - McGrath, Lauren M.
A1  - Restrepo, Sandra C. Mesa
A1  - Moessner, Rainald
A1  - Morgan, Jubel
A1  - Muller, Heike
A1  - Murphy, Dennis L.
A1  - Naarden, Allan L.
A1  - Ochoa, William Cornejo
A1  - Ophoff, Roel A.
A1  - Osiecki, Lisa
A1  - Pakstis, Andrew J.
A1  - Pato, Michele T.
A1  - Pato, Carlos N.
A1  - Piacentini, John
A1  - Pittenger, Christopher
A1  - Pollak, Yehunda
A1  - Rauch, Scott L.
A1  - Renner, Tobias J.
A1  - Reus, Victor I.
A1  - Richter, Margaret A.
A1  - Riddle, Mark A.
A1  - Robertson, Mary M.
A1  - Romero, Roxana
A1  - Rosàrio, Maria C.
A1  - Rosenberg, David
A1  - Rouleau, Guy A.
A1  - Ruhrmann, Stephan
A1  - Ruiz-Linares, Andreas
A1  - Sampaio, Aline S.
A1  - Samuels, Jack
A1  - Sandor, Paul
A1  - Sheppard, Broke
A1  - Singer, Harvey S.
A1  - Smit, Jan H.
A1  - Stein, Dan J.
A1  - Strengman, E.
A1  - Tischfield, Jay A.
A1  - Valencia Duarte, Ana V.
A1  - Vallada, Homero
A1  - Van Nieuwerburgh, Flip
A1  - Veenstra-VanderWeele, Jeremy
A1  - Walitza, Susanne
A1  - Wang, Ying
A1  - Wendland, Jens R.
A1  - Westenberg, Herman G. M.
A1  - Shugart, Yin Yao
A1  - Miguel, Euripedes C.
A1  - McMahon, William
A1  - Wagner, Michael
A1  - Nicolini, Humberto
A1  - Posthuma, Danielle
A1  - Hanna, Gregory L.
A1  - Heutink, Peter
A1  - Denys, Damiaan
A1  - Arnold, Paul D.
A1  - Oostra, Ben A.
A1  - Nestadt, Gerald
A1  - Freimer, Nelson B.
A1  - Pauls, David L.
A1  - Wray, Naomi R.
A1  - Stewart, S. Evelyn
A1  - Mathews, Carol A.
A1  - Knowles, James A.
A1  - Cox, Nancy J.
A1  - Scharf, Jeremiah M.
T1  - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
JF  - PLoS Genetics
N2  - The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
KW  - TIC disorders
KW  - missing heritability
KW  - complex diseases
KW  - neuropsychiatric disorders
KW  - common SNPS
KW  - gilles
KW  - family
KW  - brain
KW  - expression
KW  - autism
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127377
SN  - 1553-7390
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Couch, Fergus J.
A1  - Wang, Xianshu
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Olswold, Curtis
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Fredericksen, Zachary
A1  - Barrowdale, Daniel
A1  - Dennis, Joe
A1  - Gaudet, Mia M.
A1  - Dicks, Ed
A1  - Kosel, Matthew
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Lee, Adam
A1  - Bacot, Françios
A1  - Vincent, Daniel
A1  - Hogervorst, Frans B. L.
A1  - Peock, Susan
A1  - Stoppa-Lyonnet, Dominique
A1  - Jakubowska, Anna
A1  - Radice, Paolo
A1  - Schmutzler, Rita Katharina
A1  - Domchek, Susan M.
A1  - Piedmonte, Marion
A1  - Singer, Christian F.
A1  - Friedman, Eitan
A1  - Thomassen, Mads
A1  - Hansen, Thomas V. O.
A1  - Neuhausen, Susan L.
A1  - Szabo, Csilla I.
A1  - Blanco, Ingnacio
A1  - Greene, Mark H.
A1  - Karlan, Beth Y.
A1  - Garber, Judy
A1  - Phelan, Catherine M.
A1  - Weitzel, Jeffrey N.
A1  - Montagna, Marco
A1  - Olah, Edith
A1  - Andrulis, Irene L.
A1  - Godwin, Andrew K.
A1  - Yannoukakos, Drakoulis
A1  - Goldgar, David E.
A1  - Caldes, Trinidad
A1  - Nevanlinna, Heli
A1  - Osorio, Ana
A1  - Terry, Mary Beth
A1  - Daly, Mary B.
A1  - van Rensburg, Elisabeth J.
A1  - Hamann, Ute
A1  - Ramus, Susan J.
A1  - Toland, Amanda Ewart
A1  - Caligo, Maria A.
A1  - Olopade, Olufunmilayo I.
A1  - Tung, Nadine
A1  - Claes, Kathleen
A1  - Beattie, Mary S.
A1  - Southey, Melissa C.
A1  - Imyanitov, Evgeny N.
A1  - Tischkowitz, Marc
A1  - Janavicius, Ramunas
A1  - John, Esther M.
A1  - Kwong, Ava
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Balmaña, Judith
A1  - Barkardottir, Rosa B.
A1  - Arun, Banu K.
A1  - Rennert, Gad
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Campbell, Ian
A1  - van der Hout, Annemarie H.
A1  - van Deurzen, Carolien H. M.
A1  - Seynaeve, Caroline
A1  - Garcia, Encarna B. Gómez
A1  - van Leeuwen, Flora E.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Gille, Johannes J. P.
A1  - Ausems, Magreet G. E. M.
A1  - Blok, Marinus J.
A1  - Ligtenberg, Marjolinjin J. L.
A1  - Rookus, Matti A.
A1  - Devilee, Peter
A1  - Verhoef, Senno
A1  - van Os, Theo A. M.
A1  - Wijnen, Juul T.
A1  - Frost, Debra
A1  - Ellis, Steve
A1  - Fineberg, Elena
A1  - Platte, Radke
A1  - Evans, D. Gareth
A1  - Izatt, Luise
A1  - Eeles, Rosalind A.
A1  - Adlard, Julian
A1  - Eccles, Diana M.
A1  - Cook, Jackie
A1  - Brewer, Carole
A1  - Douglas, Fiona
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Side, Lucy E.
A1  - Donaldson, Alan
A1  - Houghton, Catherine
A1  - Rogers, Mark T.
A1  - Dorkins, Huw
A1  - Eason, Jacqueline
A1  - Gregory, Helen
A1  - McCann, Emma
A1  - Murray, Alex
A1  - Calender, Alain
A1  - Hardouin, Agnès
A1  - Berthet, Pascaline
A1  - Delnatte, Capucine
A1  - Nogues, Catherine
A1  - Lasset, Christine
A1  - Houdayer, Claude
A1  - Leroux,, Dominique
A1  - Rouleau, Etienne
A1  - Prieur, Fabienne
A1  - Damiola, Francesca
A1  - Sobol, Hagay
A1  - Coupier, Isabelle
A1  - Venat-Bouvet, Laurence
A1  - Castera, Laurent
A1  - Gauthier-Villars, Marion
A1  - Léoné, Mélanie
A1  - Pujol, Pascal
A1  - Mazoyer, Sylvie
A1  - Bignon, Yves-Jean
A1  - Zlowocka-Perlowska, Elzbieta
A1  - Gronwald, Jacek
A1  - Lubinski,, Jan
A1  - Durda, Katarzyna
A1  - Jaworska, Katarzyna
A1  - Huzarski, Tomasz
A1  - Spurdle, Amanda B.
A1  - Viel, Alessandra
A1  - Peissel, Bernhard
A1  - Bonanni, Bernardo
A1  - Melloni, Guilia
A1  - Ottini, Laura
A1  - Papi, Laura
A1  - Varesco, Liliana
A1  - Tibiletti, Maria Grazia
A1  - Peterlongo, Paolo
A1  - Volorio, Sara
A1  - Manoukian, Siranoush
A1  - Pensotti, Valeria
A1  - Arnold, Norbert
A1  - Engel, Christoph
A1  - Deissler, Helmut
A1  - Gadzicki, Dorothea
A1  - Gehrig, Andrea
A1  - Kast, Karin
A1  - Rhiem, Kerstin
A1  - Meindl, Alfons
A1  - Niederacher, Dieter
A1  - Ditsch, Nina
A1  - Plendl, Hansjoerg
A1  - Preisler-Adams, Sabine
A1  - Engert, Stefanie
A1  - Sutter, Christian
A1  - Varon-Mateeva, Raymenda
A1  - Wappenschmidt, Barbara
A1  - Weber, Bernhard H. F.
A1  - Arver, Brita
A1  - Stenmark-Askmalm, Marie
A1  - Loman, Niklas
A1  - Rosenquist, Richard
A1  - Einbeigi, Zakaria
A1  - Nathanson, Katherine L.
A1  - Rebbeck, Timothy R.
A1  - Blank, Stephanie V.
A1  - Cohn, David E.
A1  - Rodriguez, Gustavo C.
A1  - Small, Laurie
A1  - Friedlander, Michael
A1  - Bae-Jump, Victoria L.
A1  - Fink-Retter, Anneliese
A1  - Rappaport, Christine
A1  - Gschwantler-Kaulich, Daphne
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Lindor, Noralane M.
A1  - Kaufman, Bella
A1  - Paluch, Shani Shimon
A1  - Laitman, Yael
A1  - Skytte, Anne-Bine
A1  - Gerdes, Anne-Marie
A1  - Pedersen, Inge Sokilde
A1  - Moeller, Sanne Traasdahl
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Vijai, Joseph
A1  - Sarrel, Kara
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Ozcelik, Hilmi
A1  - Ejlertsen, Bent
A1  - Nielsen, Finn C.
A1  - Jønson, Lars
A1  - Andersen, Mette K.
A1  - Ding, Yuan Chun
A1  - Steele, Linda
A1  - Foretova, Lenka
A1  - Teulé, Alex
A1  - Lazaro, Conxi
A1  - Brunet, Joan
A1  - Pujana, Miquel Angel
A1  - Mai, Phuong L.
A1  - Loud, Jennifer T.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - Orsulic, Sandra
A1  - Narod, Steven A.
A1  - Herzog, Josef
A1  - Sand, Sharon R.
A1  - Tognazzo, Silvia
A1  - Agata, Simona
A1  - Vaszko, Tibor
A1  - Weaver, Joellen
A1  - Stravropoulou, Alexandra V.
A1  - Buys, Saundra S.
A1  - Romero, Atocha
A1  - de la Hoya, Miguel
A1  - Aittomäki, Kristiina
A1  - Muranen, Taru A.
A1  - Duran, Mercedes
A1  - Chung, Wendy K.
A1  - Lasa, Adriana
A1  - Dorfling, Cecilia M.
A1  - Miron, Alexander
A1  - Benitez, Javier
A1  - Senter, Leigha
A1  - Huo, Dezheng
A1  - Chan, Salina B.
A1  - Sokolenko, Anna P.
A1  - Chiquette, Jocelyne
A1  - Tihomirova, Laima
A1  - Friebel, Tara M.
A1  - Agnarsson, Bjarne A.
A1  - Lu, Karen H.
A1  - Lejbkowicz, Flavio
A1  - James, Paul A.
A1  - Hall, Per
A1  - Dunning, Alison M.
A1  - Tessier, Daniel
A1  - Cunningham, Julie
A1  - Slager, Susan L.
A1  - Chen, Wang
A1  - Hart, Steven
A1  - Stevens, Kristen
A1  - Simard, Jacques
A1  - Pastinen, Tomi
A1  - Pankratz, Vernon S.
A1  - Offit, Kenneth
A1  - Easton, Douglas F.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
T1  - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
JF  - PLOS Genetics
N2  - 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 x 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 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 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 association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-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.
KW  - common variants
KW  - susceptibility alleles
KW  - genetic variants
KW  - modifiers
KW  - ZNF365
KW  - investigators
KW  - population
KW  - consortium
KW  - selection
KW  - subtypes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947
SN  - 1553-7404
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Osorio, Ana
A1  - Milne, Roger L.
A1  - Kuchenbaecker, Karoline
A1  - Vaclová, Tereza
A1  - Pita, Guillermo
A1  - Alonso, Rosario
A1  - Peterlongo, Paolo
A1  - Blanco, Ignacio
A1  - de la Hoya, Miguel
A1  - Duran, Mercedes
A1  - Diez, Orland
A1  - Ramón y Cajal, Teresa
A1  - Konstantopoulou, Irene
A1  - Martínez-Bouzas, Christina
A1  - Conejero, Raquel Andrés
A1  - Soucy, Penny
A1  - McGuffog, Lesley
A1  - Barrowdale, Daniel
A1  - Lee, Andrew
A1  - Arver, Brita
A1  - Rantala, Johanna
A1  - Loman, Niklas
A1  - Ehrencrona, Hans
A1  - Olopade, Olufunmilayo I.
A1  - Beattie, Mary S.
A1  - Domchek, Susan M.
A1  - Nathanson, Katherine
A1  - Rebbeck, Timothy R.
A1  - Arun, Banu K.
A1  - Karlan, Beth Y.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - John, Esther M.
A1  - Whittemore, Alice S.
A1  - Daly, Mary B.
A1  - Southey, Melissa
A1  - Hopper, John
A1  - Terry, Mary B.
A1  - Buys, Saundra S.
A1  - Janavicius, Ramunas
A1  - Dorfling, Cecilia M.
A1  - van Rensburg, Elizabeth J.
A1  - Steele, Linda
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan Chun
A1  - Hansen, Thomas V. O.
A1  - Jønson, Lars
A1  - Ejlertsen, Bent
A1  - Gerdes, Anne-Marie
A1  - Infante, Mar
A1  - Herráez, Belén
A1  - Moreno, Leticia Thais
A1  - Weitzel, Jeffrey N.
A1  - Herzog, Josef
A1  - Weeman, Kisa
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Scuvera, Guilietta
A1  - Bonanni, Bernardo
A1  - Mariette, Frederique
A1  - Volorio, Sara
A1  - Viel, Alessandra
A1  - Varesco, Liliana
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Tibiletti, Maria Grazia
A1  - Radice, Paolo
A1  - Yannoukakos, Drakoulis
A1  - Garber, Judy
A1  - Ellis, Steve
A1  - Frost, Debra
A1  - Platte, Radka
A1  - Fineberg, Elena
A1  - Evans, Gareth
A1  - Lalloo, Fiona
A1  - Izatt, Louise
A1  - Eeles, Ros
A1  - Adlard, Julian
A1  - Davidson, Rosemarie
A1  - Cole, Trevor
A1  - Eccles, Diana
A1  - Cook, Jackie
A1  - Hodgson, Shirley
A1  - Brewer, Carole
A1  - Tischkowitz, Marc
A1  - Douglas, Fiona
A1  - Porteous, Mary
A1  - Side, Lucy
A1  - Walker, Lisa
A1  - Morrison, Patrick
A1  - Donaldson, Alan
A1  - Kennedy, John
A1  - Foo, Claire
A1  - Godwin, Andrew K.
A1  - Schmutzler, Rita Katharina
A1  - Wappenschmidt, Barbara
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Meindl, Alftons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Plendl, Hans Jörg
A1  - Niederacher, Dieter
A1  - Sutter, Christian
A1  - Wang-Gohrke, Shan
A1  - Steinemann, Doris
A1  - Preisler-Adams, Sabine
A1  - Kast, Karin
A1  - Varon-Mateeva, Raymonda
A1  - Gehrig, Andrea
A1  - Stoppa-Lyonnet, Dominique
A1  - Sinilnikova, Olga M.
A1  - Mazoyer, Sylvie
A1  - Damiola, Francesca
A1  - Poppe, Bruce
A1  - Claes, Kathleen
A1  - Piedmonte, Marion
A1  - Tucker, Kathy
A1  - Backes, Floor
A1  - Rodríguez, Gustavo
A1  - Brewster, Wendy
A1  - Wakeley, Katie
A1  - Rutherford, Thomas
A1  - Caldés, Trinidad
A1  - Nevanlinna, Heli
A1  - Aittomäki, Kristiina
A1  - Rookus, Matti A.
A1  - van Os, Theo A. M.
A1  - van der Kolk, Lizet
A1  - de Lange, J. L.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - van der Hout, A. H.
A1  - van Asperen, Christi J.
A1  - Goméz Garcia, Encarna B.
A1  - Encarna, B.
A1  - Hoogerbrugge, Nicoline
A1  - Collée, J. Margriet
A1  - van Deurzen, Carolien H. M.
A1  - van der Luijt, Rob B.
A1  - Devilee, Peter
A1  - Olah, Edith
A1  - Lázaro, Conxi
A1  - Teulé, Alex
A1  - Menéndez, Mireia
A1  - Jakubowska, Anna
A1  - Cybulski, Cezary
A1  - Gronwald, Jecek
A1  - Lubinski, Jan
A1  - Durda, Katarzyna
A1  - Jaworska-Bieniek, Katarzyna
A1  - Johannsson, Oskar Th.
A1  - Maugard, Christine
A1  - Montagna, Marco
A1  - Tognazzo, Silvia
A1  - Teixeira, Manuel R.
A1  - Healey, Sue
A1  - Olswold, Curtis
A1  - Guidugli, Lucia
A1  - Lindor, Noralane
A1  - Slager, Susan
A1  - Szabo, Csilla I.
A1  - Vijai, Joseph
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Zhang, Liying
A1  - Rau-Murthy, Rohini
A1  - Fink-Retter, Anneliese
A1  - Singer, Christine F.
A1  - Rappaport, Christine
A1  - Kaulich, Daphne Geschwantler
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Berger, Andreas
A1  - Phelan, Catherine M.
A1  - Greene, Mark H.
A1  - Mai, Phuong L.
A1  - Lejbkowicz, Flavio
A1  - Andrulis, Irene
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Toland, Amanda Ewart
A1  - Bojesen, Anders
A1  - Pedersen, Inge Sokilde
A1  - Sunde, Lone
A1  - Thomassen, Mads
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Friedman, Eitan
A1  - Laitman, Yeal
A1  - Shimon, Shanie Paluch
A1  - Simard, Jaques
A1  - Easton, Douglas F.
A1  - Offit, Kenneth
A1  - Couch, Fergus J.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
A1  - Benitez, Javier
T1  - DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
JF  - PLOS Genetics
N2  - Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
KW  - single-nucleotide polymorphisms
KW  - breast cancer
KW  - ovarian cancer
KW  - genetic modifiers
KW  - common variants
KW  - NEIL2
KW  - OGG1
KW  - investigators
KW  - consortium
KW  - damage
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116820
SN  - 1553-7404
VL  - 4
IS  - e1004256
ER  - 
TY  - JOUR
A1  - Antoniou, Antonis C.
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Beesley, Jonathan
A1  - Chen, Xiaoqing
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Barrowdale, Daniel
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Caligo, Maria A.
A1  - Loman, Niklas
A1  - Harbst, Katja
A1  - Lindblom, Annika
A1  - Arver, Brita
A1  - Rosenquist, Richard
A1  - Karlsson, Per
A1  - Nathanson, Kate
A1  - Domchek, Susan
A1  - Rebbeck, Tim
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Jaworska, Katarzyna
A1  - Durda, Katarzyna
A1  - Zlowowcka-Perłowska, Elżbieta
A1  - Osorio, Ana
A1  - Durán, Mercedes
A1  - Andrés, Raquel
A1  - Benítez, Javier
A1  - Hamann, Ute
A1  - Hogervorst, Frans B.
A1  - van Os, Theo A.
A1  - Verhoef, Senno
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Wijnen, Juul
A1  - Garcia, Encarna B. Gómez
A1  - Ligtenberg, Marjolijn J.
A1  - Kriege, Mieke
A1  - Collée, Margriet
A1  - Ausems, Margreet G. E. M.
A1  - Oosterwijk, Jan C.
A1  - Peock, Susan
A1  - Frost, Debra
A1  - Ellis, Steve D.
A1  - Platte, Radka
A1  - Fineberg, Elena
A1  - Evans, D. Gareth
A1  - Lalloo, Fiona
A1  - Jacobs, Chris
A1  - Eeles, Ros
A1  - Adlard, Julian
A1  - Davidson, Rosemarie
A1  - Cole, Trevor
A1  - Cook, Jackie
A1  - Paterson, Joan
A1  - Douglas, Fiona
A1  - Brewer, Carole
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Walker, Lisa
A1  - Rogers, Mark T.
A1  - Donaldson, Alan
A1  - Dorkins, Huw
A1  - Godwin, Andrew K.
A1  - Bove, Betsy
A1  - Stoppa-Lyonnet, Dominique
A1  - Houdayer, Claude
A1  - Buecher, Bruno
A1  - de Pauw, Antoine
A1  - Mazoyer, Sylvie
A1  - Calender, Alain
A1  - Léoné, Mélanie
A1  - Bressac-de Paillerets, Brigitte
A1  - Caron, Olivier
A1  - Sobol, Hagay
A1  - Frenay, Marc
A1  - Prieur, Fabienne
A1  - Ferrer, Sandra Fert
A1  - Mortemousque, Isabelle
A1  - Buys, Saundra
A1  - Daly, Mary
A1  - Miron, Alexander
A1  - Terry, Mary Beth
A1  - Hopper, John L.
A1  - John, Esther M.
A1  - Southey, Melissa
A1  - Goldgar, David
A1  - Singer, Christian F.
A1  - Fink-Retter, Anneliese
A1  - Muy-Kheng, Tea
A1  - Geschwantler Kaulich, Daphne
A1  - Hansen, Thomas V. O.
A1  - Nielsen, Finn C.
A1  - Barkardottir, Rosa B.
A1  - Gaudet, Mia
A1  - Kirchhoff, Tomas
A1  - Joseph, Vijai
A1  - Dutra-Clarke, Ana
A1  - Offit, Kenneth
A1  - Piedmonte, Marion
A1  - Kirk, Judy
A1  - Cohn, David
A1  - Hurteau, Jean
A1  - Byron, John
A1  - Fiorica, James
A1  - Toland, Amanda E.
A1  - Montagna, Marco
A1  - Oliani, Cristina
A1  - Imyanitov, Evgeny
A1  - Isaacs, Claudine
A1  - Tihomirova, Laima
A1  - Blanco, Ignacio
A1  - Lazaro, Conxi
A1  - Teulé, Alex
A1  - Del Valle, J.
A1  - Gayther, Simon A.
A1  - Odunsi, Kunle
A1  - Gross, Jenny
A1  - Karlan, Beth Y.
A1  - Olah, Edith
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Beattie, Mary S.
A1  - Dorfling, Cecelia M.
A1  - Jansen van Rensburg, Elizabeth
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Schmutzler, Rita K.
A1  - Wappenschmidt, Barbara
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Heidemann, Simone
A1  - Niederacher, Dieter
A1  - Preisler-Adams, Sabine
A1  - Gadzicki, Dorothea
A1  - Varon-Mateeva, Raymonda
A1  - Deissler, Helmut
A1  - Gehrig, Andrea
A1  - Sutter, Christian
A1  - Kast, Karin
A1  - Fiebig, Britta
A1  - Schäfer, Dieter
A1  - Caldes, Trinidad
A1  - de la Hoya, Miguel
A1  - Nevanlinna, Heli
A1  - Muranen, Taru A.
A1  - Lespérance, Bernard
A1  - Spurdle, Amanda B.
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan C.
A1  - Wang, Xianshu
A1  - Fredericksen, Zachary
A1  - Pankratz, Vernon S.
A1  - Lindor, Noralane M.
A1  - Peterlongo, Paulo
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Bonanni, Bernardo
A1  - Bernard, Loris
A1  - Dolcetti, Riccardo
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Radice, Paolo
A1  - Greene, Mark H.
A1  - Loud, Jennifer T.
A1  - Andrulis, Irene L.
A1  - Ozcelik, Hilmi
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Thomassen, Mads
A1  - Gerdes, Anne-Marie
A1  - Jensen, Uffe B.
A1  - Skytte, Anne-Bine
A1  - Kruse, Torben A.
A1  - Chenevix-Trench, Georgia
A1  - Couch, Fergus J.
A1  - Simard, Jacques
A1  - Easton, Douglas F.
T1  - Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
JF  - Breast Cancer Research
N2  - 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.
KW  - investigators
KW  - genetic modifiers
KW  - mammographic density
KW  - susceptibility loci
KW  - ovarian cancer
KW  - hormone-related protein
KW  - genome-wide association
KW  - tumor subtypes
KW  - alleles
KW  - consortium
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130449
VL  - 14
IS  - R33
ER  - 
TY  - JOUR
A1  - Blein, Sophie
A1  - Bardel, Claire
A1  - Danjean, Vincent
A1  - McGuffog, Lesley
A1  - Healay, Sue
A1  - Barrowdale, Daniel
A1  - Lee, Andrew
A1  - Dennis, Joe
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Terry, Mary Beth
A1  - Chung, Wendy K.
A1  - Goldgar, David E.
A1  - Buys, Saundra S.
A1  - Janavicius, Ramunas
A1  - Tihomirova, Laima
A1  - Tung, Nadine
A1  - Dorfling, Cecilia M.
A1  - van Rensburg, Elizabeth J.
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan Chun
A1  - Gerdes, Anne-Marie
A1  - Ejlertsen, Bent
A1  - Nielsen, Finn C.
A1  - Hansen, Thomas V. O.
A1  - Osorio, Ana
A1  - Benitez, Javier
A1  - Andreas Conejero, Raquel
A1  - Segota, Ena
A1  - Weitzel, Jeffrey N.
A1  - Thelander, Margo
A1  - Peterlongo, Paolo
A1  - Radice, Paolo
A1  - Pensotti, Valeria
A1  - Dolcetti, Riccardo
A1  - Bonanni, Bernardo
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Scuvera, Giulietta
A1  - Manoukian, Siranoush
A1  - Varesco, Liliana
A1  - Capone, Gabriele L.
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Yannoukakos, Drakoulis
A1  - Konstantopoulou, Irene
A1  - Garber, Judy
A1  - Hamann, Ute
A1  - Donaldson, Alan
A1  - Brady, Angela
A1  - Brewer, Carole
A1  - Foo, Claire
A1  - Evans, D. Gareth
A1  - Frost, Debra
A1  - Eccles, Diana
A1  - Douglas, Fiona
A1  - Cook, Jackie
A1  - Adlard, Julian
A1  - Barwell, Julian
A1  - Walker, Lisa
A1  - Izatt, Louise
A1  - Side, Lucy E.
A1  - Kennedy, M. John
A1  - Tischkowitz, Marc
A1  - Rogers, Mark T.
A1  - Porteous, Mary E.
A1  - Morrison, Patrick J.
A1  - Platte, Radka
A1  - Eeles, Ros
A1  - Davidson, Rosemarie
A1  - Hodgson, Shirley
A1  - Cole, Trevor
A1  - Godwin, Andrew K
A1  - Isaacs, Claudine
A1  - Claes, Kathleen
A1  - De Leeneer, Kim
A1  - Meindl, Alfons
A1  - Gehrig, Andrea
A1  - Wappenschmidt, Barbara
A1  - Sutter, Christian
A1  - Engel, Christoph
A1  - Niederacher, Dieter
A1  - Steinemann, Doris
A1  - Plendl, Hansjoerg
A1  - Kast, Karin
A1  - Rhiem, Kerstin
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Varon-Mateeva, Raymonda
A1  - Schmutzler, Rita K.
A1  - Preisler-Adams, Sabine
A1  - Markov, Nadja Bogdanova
A1  - Wang-Gohrke, Shan
A1  - de Pauw, Antoine
A1  - Lefol, Cedrick
A1  - Lasset, Christine
A1  - Leroux, Dominique
A1  - Rouleau, Etienne
A1  - Damiola, Francesca
A1  - Dreyfus, Helene
A1  - Barjhoux, Laure
A1  - Golmard, Lisa
A1  - Uhrhammer, Nancy
A1  - Bonadona, Valerie
A1  - Sornin, Valerie
A1  - Bignon, Yves-Jean
A1  - Carter, Jonathan
A1  - Van Le, Linda
A1  - Piedmonte, Marion
A1  - DiSilvestro, Paul A.
A1  - de la Hoya, Miguel
A1  - Caldes, Trinidad
A1  - Nevanlinna, Heli
A1  - Aittomäki, Kristiina
A1  - Jager, Agnes
A1  - van den Ouweland, Ans M. W.
A1  - Kets, Carolien M.
A1  - Aalfs, Cora M.
A1  - van Leeuwen, Flora E.
A1  - Hogervorst, Frans B. L.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Oosterwijk, Jan C.
A1  - van Roozendaal, Kees E. P.
A1  - Rookus, Matti A.
A1  - Devilee, Peter
A1  - van der Luijt, Rob B.
A1  - Olah, Edith
A1  - Diez, Orland
A1  - Teule, Alex
A1  - Lazaro, Conxi
A1  - Blanco, Ignacio
A1  - Del Valle, Jesus
A1  - Jakubowska, Anna
A1  - Sukiennicki, Grzegorz
A1  - Gronwald, Jacek
A1  - Spurdle, Amanda B.
A1  - Foulkes, William
A1  - Olswold, Curtis
A1  - Lindor, Noralene M.
A1  - Pankratz, Vernon S.
A1  - Szabo, Csilla I.
A1  - Lincoln, Anne
A1  - Jacobs, Lauren
A1  - Corines, Marina
A1  - Robson, Mark
A1  - Vijai, Joseph
A1  - Berger, Andreas
A1  - Fink-Retter, Anneliese
A1  - Singer, Christian F.
A1  - Rappaport, Christine
A1  - Geschwantler Kaulich, Daphne
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Greene, Mark H.
A1  - Mai, Phuong L.
A1  - Rennert, Gad
A1  - Imyanitov, Evgeny N.
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Andrulis, Irene L.
A1  - Tchatchou, Andrine
A1  - Toland, Amanda Ewart
A1  - Pedersen, Inge Sokilde
A1  - Thomassen, Mads
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Caligo, Maria A.
A1  - Friedman, Eitan
A1  - Zidan, Jamal
A1  - Laitman, Yael
A1  - Lindblom, Annika
A1  - Melin, Beatrice
A1  - Arver, Brita
A1  - Loman, Niklas
A1  - Rosenquist, Richard
A1  - Olopade, Olufunmilayo I.
A1  - Nussbaum, Robert L.
A1  - Ramus, Susan J.
A1  - Nathanson, Katherine L.
A1  - Domchek, Susan M.
A1  - Rebbeck, Timothy R.
A1  - Arun, Banu K.
A1  - Mitchell, Gillian
A1  - Karlan, Bethy Y.
A1  - Lester, Jenny
A1  - Orsulic, Sandra
A1  - Stoppa-Lyonnet, Dominique
A1  - Thomas, Gilles
A1  - Simard, Jacques
A1  - Couch, Fergus J.
A1  - Offit, Kenenth
A1  - Easton, Douglas F.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
A1  - Mazoyer, Sylvie
A1  - Phelan, Catherine M.
A1  - Sinilnikova, Olga M.
A1  - Cox, David G.
T1  - An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
JF  - Breast Cancer Research
N2  - 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 effects.
KW  - single-nucleotide polymorphisms
KW  - genetic modifiers
KW  - oxidative stress
KW  - consortium
KW  - multiple diseases
KW  - DNA
KW  - haplogroups
KW  - susceptibility
KW  - Ovarian
KW  - variants
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145458
VL  - 17
IS  - 61
ER  - 
TY  - JOUR
A1  - Blanco, Ignacio
A1  - Kuchenbaecker, Karoline
A1  - Cuadras, Daniel
A1  - Wang, Xianshu
A1  - Barrowdale, Daniel
A1  - Ruiz de Garibay, Gorka
A1  - Librado, Pablo
A1  - Sanchez-Gracia, Alejandro
A1  - Rozas, Julio
A1  - Bonifaci, Núria
A1  - McGuffog, Lesley
A1  - Pankratz, Vernon S.
A1  - Islam, Abul
A1  - Mateo, Francesca
A1  - Berenguer, Antoni
A1  - Petit, Anna
A1  - Català, Isabel
A1  - Brunet, Joan
A1  - Feliubadaló, Lidia
A1  - Tornero, Eva
A1  - Benítez, Javier
A1  - Osorio, Ana
A1  - Ramón y Cajal, Teresa
A1  - Nevanlinna, Heli
A1  - Aittomäki, Kristina
A1  - Arun, Banu K.
A1  - Toland, Amanda E.
A1  - Karlan, Beth Y.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - Greene, Mark H.
A1  - Mai, Phuong L.
A1  - Nussbaum, Robert L.
A1  - Andrulis, Irene L.
A1  - Domchek, Susan M.
A1  - Nathanson, Katherine L.
A1  - Rebbeck, Timothy R.
A1  - Barkardottir, Rosa B.
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Durda, Katarzyna
A1  - Jaworska-Bieniek, Katarzyna
A1  - Claes, Kathleen
A1  - Van Maerken, Tom
A1  - Díez, Orland
A1  - Hansen, Thomas V.
A1  - Jønson, Lars
A1  - Gerdes, Anne-Marie
A1  - Ejlertsen, Bent
A1  - De la Hoya, Miguel
A1  - Caldés, Trinidad
A1  - Dunning, Alison M.
A1  - Oliver, Clare
A1  - Fineberg, Elena
A1  - Cook, Margaret
A1  - Peock, Susan
A1  - McCann, Emma
A1  - Murray, Alex
A1  - Jacobs, Chris
A1  - Pichert, Gabriella
A1  - Lalloo, Fiona
A1  - Chu, Carol
A1  - Dorkins, Huw
A1  - Paterson, Joan
A1  - Ong, Kai-Ren
A1  - Teixeira, Manuel R.
A1  - Hogervorst, Frans B. L.
A1  - Van der Hout, Annemarie H.
A1  - Seynaeve, Caroline
A1  - Van der Luijt, Rob B.
A1  - Ligtenberg, Marjolijn J. L.
A1  - Devilee, Peter
A1  - Wijnen, Juul T.
A1  - Rookus, Matti A.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Blok, Marinus J.
A1  - Van den Ouweland, Ans M. W.
A1  - Aalfs, Cora M.
A1  - Rodriguez, Gustavo C.
A1  - Phillips, Kelly-Anne A.
A1  - Piedmonte, Marion
A1  - Nerenstone, Stacy R.
A1  - Bae-Jump, Victoria L.
A1  - O'Malley, David M.
A1  - Schmutzler, Rita K.
A1  - Wappenschmidt, Barbara
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Plendl, Hansjoerg J.
A1  - Niederacher, Dieter
A1  - Sutter, Christian
A1  - Wang-Gohrke, Shan
A1  - Steinemann, Doris
A1  - Preisler-Adams, Sabine
A1  - Kast, Karin
A1  - Varon-Mateeva, Raymonda
A1  - Gehrig, Andrea
A1  - Bojesen, Anders
A1  - Pedersen, Inge Sokilde
A1  - Sunde, Lone
A1  - Birk Jensen, Uffe
A1  - Thomassen, Mads
A1  - Kruse, Torben A.
A1  - Foretova, Lenka
A1  - Peterlongo, Paolo
A1  - Bernard, Loris
A1  - Peissel, Bernard
A1  - Scuvera, Giulietta
A1  - Manoukian, Siranoush
A1  - Radice, Paolo
A1  - Ottini, Laura
A1  - Montagna, Marco
A1  - Agata, Simona
A1  - Maugard, Christine
A1  - Simard, Jacques
A1  - Soucy, Penny
A1  - Berger, Andreas
A1  - Fink-Retter, Anneliese
A1  - Singer, Christian F.
A1  - Rappaport, Christine
A1  - Geschwantler-Kaulich, Daphne
A1  - Tea, Muy-Kheng
A1  - Pfeiler, Georg
A1  - John, Esther M.
A1  - Miron, Alex
A1  - Neuhausen, Susan L.
A1  - Terry, Mary Beth
A1  - Chung, Wendy K.
A1  - Daly, Mary B.
A1  - Goldgar, David E.
A1  - Janavicius, Ramunas
A1  - Dorfling, Cecilia M.
A1  - Van Rensburg, Elisabeth J.
A1  - Fostira, Florentia
A1  - Konstantopoulou, Irene
A1  - Garber, Judy
A1  - Godwin, Andrew K.
A1  - Olah, Edith
A1  - Narod, Steven A.
A1  - Rennert, Gad
A1  - Paluch, Shani Shimon
A1  - Laitman, Yael
A1  - Friedman, Eitan
A1  - Liljegren, Annelie
A1  - Rantala, Johanna
A1  - Stenmark-Askmalm, Marie
A1  - Loman, Niklas
A1  - Imyanitov, Evgeny N.
A1  - Hamann, Ute
A1  - Spurdle, Amanda B.
A1  - Healey, Sue
A1  - Weitzel, Jeffrey N.
A1  - Herzog, Josef
A1  - Margileth, David
A1  - Gorrini, Chiara
A1  - Esteller, Manel
A1  - Gómez, Antonio
A1  - Sayols, Sergi
A1  - Vidal, Enrique
A1  - Heyn, Holger
A1  - Stoppa-Lyonnet, Dominique
A1  - Léoné, Melanie
A1  - Barjhoux, Laure
A1  - Fassy-Colcombet, Marion
A1  - Pauw, Antoine de
A1  - Lasset, Christine
A1  - Fert Ferrer, Sandra
A1  - Castera, Laurent
A1  - Berthet, Pascaline
A1  - Cornelis, François
A1  - Bignon, Yves-Jean
A1  - Damiola, Francesca
A1  - Mazoyer, Sylvie
A1  - Sinilnikova, Olga M.
A1  - Maxwell, Christopher A.
A1  - Vijai, Joseph
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Corines, Marina J.
A1  - Villano, Danylko
A1  - Cunningham, Julie
A1  - Lee, Adam
A1  - Lindor, Noralane
A1  - Lázaro, Conxi
A1  - Easton, Douglas F.
A1  - Offit, Kenneth
A1  - Chenevix-Trench, Georgia
A1  - Couch, Fergus J.
A1  - Antoniou, Antonis C.
A1  - Pujana, Miguel Angel
T1  - Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
JF  - PLoS ONE
N2  - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
KW  - genetic interaction networks
KW  - genome-wide association
KW  - expression signature
KW  - susceptibility loci
KW  - survival
KW  - modifiers
KW  - polymorphism
KW  - cell
KW  - chip-seq
KW  - elements
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143469
VL  - 10
IS  - 4
ER  - 
TY  - JOUR
A1  - Kruse, N.
A1  - Shen, B. J.
A1  - Arnold, S.
A1  - Tony, H. P.
A1  - Müller, T.
A1  - Sebald, Walter
T1  - Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation
N2  - Interleukin 4 (IL-4) exerts a decisive role in the coord.ination of proteelive immune responses against parasites, particularly helminths. A disregulation of ll.r4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human ll.r4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the ll.r4 receptor (IL-4ReJ. In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T -cell proliferation and B-eeil CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type).ß.A variants affected at site 2 exhibited partial agonist activity during T -cell proliferation; however, they still bound with high affinity to IL-4Rex. [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO }., 11, 3237-3244)]. These findings indicate that IL-4 functions by bind.ing IL-4Rex via site 1 which is constituted by residues on helices A and C. They further suggest that the association of a second, still undetined receptor protein with site 2 in helix D activates the receptor system and generates a transmembrane signal.
KW  - Biochemie
KW  - drug design/partial agonists
KW  - receptor signalling
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62451
ER  - 
TY  - JOUR
A1  - Reusch, P.
A1  - Arnold, S.
A1  - Heusser, C.
A1  - Wagner, K.
A1  - Weston, B.
A1  - Sebald, Walter
T1  - Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4
N2  - Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62418
ER  - 
TY  - JOUR
A1  - Marenholz, Ingo
A1  - Esparza-Gordillo, Jorge
A1  - Rüschendorf, Franz
A1  - Bauerfeind, Anja
A1  - Strachan, David P.
A1  - Spycher, Ben D.
A1  - Baurecht, Hansjörg
A1  - Magaritte-Jeannin, Patricia
A1  - Sääf, Annika
A1  - Kerkhof, Marjan
A1  - Ege, Markus
A1  - Baltic, Svetlana
A1  - Matheson, Melanie C.
A1  - Li, Jin
A1  - Michel, Sven
A1  - Ang, Wei Q.
A1  - McArdle, Wendy
A1  - Arnold, Andreas
A1  - Homuth, Georg
A1  - Demenais, Florence
A1  - Bouzigon, Emmanuelle
A1  - Söderhäll, Cilla
A1  - Pershagen, Göran
A1  - de Jongste, Johan C.
A1  - Postma, Dirkje S.
A1  - Braun-Fahrländer, Charlotte
A1  - Horak, Elisabeth
A1  - Ogorodova, Ludmila M.
A1  - Puzyrev, Valery P.
A1  - Bragina, Elena Yu
A1  - Hudson, Thomas J.
A1  - Morin, Charles
A1  - Duffy, David L.
A1  - Marks, Guy B.
A1  - Robertson, Colin F.
A1  - Montgomery, Grant W.
A1  - Musk, Bill
A1  - Thompson, Philip J.
A1  - Martin, Nicholas G.
A1  - James, Alan
A1  - Sleiman, Patrick
A1  - Toskala, Elina
A1  - Rodriguez, Elke
A1  - Fölster-Holst, Regina
A1  - Franke, Andre
A1  - Lieb, Wolfgang
A1  - Gieger, Christian
A1  - Heinzmann, Andrea
A1  - Rietschel, Ernst
A1  - Keil, Thomas
A1  - Cichon, Sven
A1  - Nöthen, Markus M.
A1  - Pennel, Craig E.
A1  - Sly, Peter D.
A1  - Schmidt, Carsten O.
A1  - Matanovic, Anja
A1  - Schneider, Valentin
A1  - Heinig, Matthias
A1  - Hübner, Norbert
A1  - Holt, Patrick G.
A1  - Lau, Susanne
A1  - Kabesch, Michael
A1  - Weidinger, Stefan
A1  - Hakonarson, Hakon
A1  - Ferreira, Manuel A. R.
A1  - Laprise, Catherine
A1  - Freidin, Maxim B.
A1  - Genuneit, Jon
A1  - Koppelman, Gerard H.
A1  - Melén, Erik
A1  - Dizier, Marie-Hélène
A1  - Henderson, A. John
A1  - Lee, Young Ae
T1  - Meta-analysis identifies seven susceptibility loci involved in the atopic march
JF  - Nature Communications
N2  - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
KW  - chromosome 11Q13
KW  - risk
KW  - genomewide association
KW  - hay fever
KW  - birth cohort
KW  - filaggrin mutations
KW  - food allergy
KW  - juvenile myoclonic epilepsy
KW  - childhood asthma
KW  - dermatitis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835
VL  - 6
IS  - 8804
ER  - 
TY  - JOUR
A1  - Silvestri, Valentina
A1  - Barrowdale, Daniel
A1  - Mulligan, Anna Marie
A1  - Neuhausen, Susan L.
A1  - Fox, Stephen
A1  - Karlan, Beth Y.
A1  - Mitchell, Gillian
A1  - James, Paul
A1  - Thull, Darcy L.
A1  - Zorn, Kristin K.
A1  - Carter, Natalie J.
A1  - Nathanson, Katherine L.
A1  - Domchek, Susan M.
A1  - Rebbeck, Timothy R.
A1  - Ramus, Susan J.
A1  - Nussbaum, Robert L.
A1  - Olopade, Olufunmilayo I.
A1  - Rantala, Johanna
A1  - Yoon, Sook-Yee
A1  - Caligo, Maria A.
A1  - Spugnesi, Laura
A1  - Bojesen, Anders
A1  - Pedersen, Inge Sokilde
A1  - Thomassen, Mads
A1  - Jensen, Uffe Birk
A1  - Toland, Amanda Ewart
A1  - Senter, Leigha
A1  - Andrulis, Irene L.
A1  - Glendon, Gord
A1  - Hulick, Peter J.
A1  - Imyanitov, Evgeny N.
A1  - Greene, Mark H.
A1  - Mai, Phuong L.
A1  - Singer, Christian F.
A1  - Rappaport-Fuerhauser, Christine
A1  - Kramer, Gero
A1  - Vijai, Joseph
A1  - Offit, Kenneth
A1  - Robson, Mark
A1  - Lincoln, Anne
A1  - Jacobs, Lauren
A1  - Machackova, Eva
A1  - Foretova, Lenka
A1  - Navratilova, Marie
A1  - Vasickova, Petra
A1  - Couch, Fergus J.
A1  - Hallberg, Emily
A1  - Ruddy, Kathryn J.
A1  - Sharma, Priyanka
A1  - Kim, Sung-Won
A1  - Teixeira, Manuel R.
A1  - Pinto, Pedro
A1  - Montagna, Marco
A1  - Matricardi, Laura
A1  - Arason, Adalgeir
A1  - Johannsson, Oskar Th
A1  - Barkardottir, Rosa B.
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Izquierdo, Angel
A1  - Pujana, Miguel Angel
A1  - Balmaña, Judith
A1  - Diez, Orland
A1  - Ivady, Gabriella
A1  - Papp, Janos
A1  - Olah, Edith
A1  - Kwong, Ava
A1  - Nevanlinna, Heli
A1  - Aittomäki, Kristiina
A1  - Segura, Pedro Perez
A1  - Caldes, Trinidad
A1  - Van Maerken, Tom
A1  - Poppe, Bruce
A1  - Claes, Kathleen B. M.
A1  - Isaacs, Claudine
A1  - Elan, Camille
A1  - Lasset, Christine
A1  - Stoppa-Lyonnet, Dominique
A1  - Barjhoux, Laure
A1  - Belotti, Muriel
A1  - Meindl, Alfons
A1  - Gehrig, Andrea
A1  - Sutter, Christian
A1  - Engel, Christoph
A1  - Niederacher, Dieter
A1  - Steinemann, Doris
A1  - Hahnen, Eric
A1  - Kast, Karin
A1  - Arnold, Norbert
A1  - Varon-Mateeva, Raymonda
A1  - Wand, Dorothea
A1  - Godwin, Andrew K.
A1  - Evans, D. Gareth
A1  - Frost, Debra
A1  - Perkins, Jo
A1  - Adlard, Julian
A1  - Izatt, Louise
A1  - Platte, Radka
A1  - Eeles, Ros
A1  - Ellis, Steve
A1  - Hamann, Ute
A1  - Garber, Judy
A1  - Fostira, Florentia
A1  - Fountzilas, George
A1  - Pasini, Barbara
A1  - Giannini, Giuseppe
A1  - Rizzolo, Piera
A1  - Russo, Antonio
A1  - Cortesi, Laura
A1  - Papi, Laura
A1  - Varesco, Liliana
A1  - Palli, Domenico
A1  - Zanna, Ines
A1  - Savarese, Antonella
A1  - Radice, Paolo
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Barile, Monica
A1  - Bonanni, Bernardo
A1  - Viel, Alessandra
A1  - Pensotti, Valeria
A1  - Tommasi, Stefania
A1  - Peterlongo, Paolo
A1  - Weitzel, Jeffrey N.
A1  - Osorio, Ana
A1  - Benitez, Javier
A1  - McGuffog, Lesley
A1  - Healey, Sue
A1  - Gerdes, Anne-Marie
A1  - Ejlertsen, Bent
A1  - Hansen, Thomas V. O.
A1  - Steele, Linda
A1  - Ding, Yuan Chun
A1  - Tung, Nadine
A1  - Janavicius, Ramunas
A1  - Goldgar, David E.
A1  - Buys, Saundra S.
A1  - Daly, Mary B.
A1  - Bane, Anita
A1  - Terry, Mary Beth
A1  - John, Esther M.
A1  - Southey, Melissa
A1  - Easton, Douglas F.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
A1  - Ottini, Laura
T1  - Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
JF  - Breast Cancer Research
N2  - Background

BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).

Methods

We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.

Results

Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12).

Conclusions

On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.
KW  - Male breast cancer
KW  - BRCA1/2
KW  - Pathology
KW  - Histologic grade
KW  - Genotype–phenotype correlations
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164769
VL  - 18
IS  - 15
ER  - 
TY  - JOUR
A1  - Gratwohl, A
A1  - Pfirrmann, M
A1  - Zander, A
A1  - Kröger, N
A1  - Beelen, D
A1  - Novotny, J
A1  - Nerl, C
A1  - Scheid, C
A1  - Spiekermann, K
A1  - Mayer, J
A1  - Sayer, HG
A1  - Falge, C
A1  - Bunjes, D
A1  - Döhner, H
A1  - Ganser, A
A1  - Schmidt-Wolf, I
A1  - Schwerdtfeger, R
A1  - Baurmann, H
A1  - Kuse, R
A1  - Schmitz, N
A1  - Wehmeier, A
A1  - Fischer, J Th
A1  - Ho, AD
A1  - Wilhelm, M
A1  - Goebeler, M-E
A1  - Lindemann, HW
A1  - Bormann, M
A1  - Hertenstein, B
A1  - Schlimok, G
A1  - Baerlocher, GM
A1  - Aul, C
A1  - Pfreundschuh, M
A1  - Fabian, M
A1  - Staib, P
A1  - Edinger, M
A1  - Schatz, M
A1  - Fauser, A
A1  - Arnold, R
A1  - Kindler, T
A1  - Wulf, G
A1  - Rosselet, A
A1  - Hellmann, A
A1  - Schäfer, E
A1  - Prümmer, O
A1  - Schenk, M
A1  - Hasford, J
A1  - Heimpel, H
A1  - Hossfeld, DK
A1  - Kolb, H-J
A1  - Büsche, G
A1  - Haferlach, C
A1  - Schnittger, S
A1  - Müller, MC
A1  - Reiter, A
A1  - Berger, U
A1  - Saußele, S
A1  - Hochhaus, A
A1  - Hehlmann, R
T1  - Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment
JF  - Leukemia
N2  - Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69–0.82) vs 0.69 (95% CI: 0.61–0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P = 0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
KW  - chronic myeloid leukemia
KW  - stem cell transplantation
KW  - drug treatment
KW  - CML
KW  - tyrosine kinase inhibitors
KW  - allogeneic hematopoietic stem cell transplantation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150368
VL  - 30
ER  - 
TY  - JOUR
A1  - Waider, J
A1  - Popp, S
A1  - Lange, MD
A1  - Kern, R
A1  - Kolter, JF
A1  - Kobler, J
A1  - Donner, NC
A1  - Lowe, KR
A1  - Malzbender, JH
A1  - Brazell, CJ
A1  - Arnold, MR
A1  - Aboagye, B
A1  - Schmitt-Böhrer, A
A1  - Lowry, CA
A1  - Pape, HC
A1  - Lesch, KP
T1  - Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice
JF  - Translational Psychiatry
N2  - Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2\(^{-/-}\)) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsynaptic currents on principal neurons in the basolateral nucleus, which may explain increased fear associated with hyperlocomotion and escape-like responses in aversive inescapable contexts. In contrast, lifelong 5-HT deficiency as observed in Tph2 heterozygous mice (Tph\(^{+/-}\)) is able to be compensated through reduced GABAergic transmission in the basolateral nucleus of the amygdala based on Slc6a4 mRNA upregulation in subdivisions of dorsal raphe neurons. This results in increased activity of the basolateral nucleus of the amygdala due to associated foot shock. In conclusion, our results reflect characteristic syndromal dimensions of panic disorder and agoraphobia. Thus, constitutive lack of 5-HT synthesis influence the risk for anxiety- and stressor-related disorders including panic disorder and comorbid agoraphobia through the absence of GABAergic-dependent compensatory mechanisms in the basolateral nucleus of the amygdala.
KW  - anxiety
KW  - stress
KW  - serotonin
KW  - genetics
KW  - mice
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170239
VL  - 7
IS  - e1246
ER  -