TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  - 
TY  - JOUR
A1  - Hoffmann, Linda S
A1  - Schmidt, Peter M
A1  - Keim, Yvonne
A1  - Hoffmann, Carsten
A1  - Schmidt, Harald H H W
A1  - Stasch, Johannes-Peter
T1  - Fluorescence Dequenching Makes Haem-Free Soluble Guanylate Cyclase Detectable in Living Cells
JF  - PLOS ONE
N2  - In cardiovascular disease, the protective NO/sGC/cGMP signalling-pathway is impaired due to a decreased pool of NO-sensitive haem-containing sGC accompanied by a reciprocal increase in NO-insensitive haem-free sGC. However, no direct method to detect cellular haem-free sGC other than its activation by the new therapeutic class of haem mimetics, such as BAY 58-2667, is available. Here we show that fluorescence dequenching, based on the interaction of the optical active prosthetic haem group and the attached biarsenical fluorophor FlAsH can be used to detect changes in cellular sGC haem status. The partly overlap of the emission spectrum of haem and FlAsH allows energy transfer from the fluorophore to the haem which reduces the intensity of FlAsH fluorescence. Loss of the prosthetic group, e. g. by oxidative stress or by replacement with the haem mimetic BAY 58-2667, prevented the energy transfer resulting in increased fluorescence. Haem loss was corroborated by an observed decrease in NO-induced sGC activity, reduced sGC protein levels, and an increased effect of BAY 58-2667. The use of a haem-free sGC mutant and a biarsenical dye that was not quenched by haem as controls further validated that the increase in fluorescence was due to the loss of the prosthetic haem group. The present approach is based on the cellular expression of an engineered sGC variant limiting is applicability to recombinant expression systems. Nevertheless, it allows to monitor sGC's redox regulation in living cells and future enhancements might be able to extend this approach to in vivo conditions.
KW  - spontaneously hypersensitive-rats
KW  - nitric-oxide
KW  - down-regulation
KW  - energy-transfer
KW  - cyclic-gmp
KW  - protein
KW  - activation
KW  - identification
KW  - in-vivo
KW  - no
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139631
VL  - 6
IS  - 8
ER  - 
TY  - JOUR
A1  - Dumont, Martine
A1  - Weber-Lassalle, Nana
A1  - Joly-Beauparlant, Charles
A1  - Ernst, Corinna
A1  - Droit, Arnaud
A1  - Feng, Bing-Jian
A1  - Dubois, Stéphane
A1  - Collin-Deschesnes, Annie-Claude
A1  - Soucy, Penny
A1  - Vallée, Maxime
A1  - Fournier, Frédéric
A1  - Lemaçon, Audrey
A1  - Adank, Muriel A.
A1  - Allen, Jamie
A1  - Altmüller, Janine
A1  - Arnold, Norbert
A1  - Ausems, Margreet G. E. M.
A1  - Berutti, Riccardo
A1  - Bolla, Manjeet K.
A1  - Bull, Shelley
A1  - Carvalho, Sara
A1  - Cornelissen, Sten
A1  - Dufault, Michael R.
A1  - Dunning, Alison M.
A1  - Engel, Christoph
A1  - Gehrig, Andrea
A1  - Geurts-Giele, Willemina R. R.
A1  - Gieger, Christian
A1  - Green, Jessica
A1  - Hackmann, Karl
A1  - Helmy, Mohamed
A1  - Hentschel, Julia
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hooning, Maartje J.
A1  - Horváth, Judit
A1  - Ikram, M. Arfan
A1  - Kaulfuß, Silke
A1  - Keeman, Renske
A1  - Kuang, Da
A1  - Luccarini, Craig
A1  - Maier, Wolfgang
A1  - Martens, John W. M.
A1  - Niederacher, Dieter
A1  - Nürnberg, Peter
A1  - Ott, Claus-Eric
A1  - Peters, Annette
A1  - Pharoah, Paul D. P.
A1  - Ramirez, Alfredo
A1  - Ramser, Juliane
A1  - Riedel-Heller, Steffi
A1  - Schmidt, Gunnar
A1  - Shah, Mitul
A1  - Scherer, Martin
A1  - Stäbler, Antje
A1  - Strom, Tim M.
A1  - Sutter, Christian
A1  - Thiele, Holger
A1  - van Asperen, Christi J.
A1  - van der Kolk, Lizet
A1  - van der Luijt, Rob B.
A1  - Volk, Alexander E.
A1  - Wagner, Michael
A1  - Waisfisz, Quinten
A1  - Wang, Qin
A1  - Wang-Gohrke, Shan
A1  - Weber, Bernhard H. F.
A1  - Devilee, Peter
A1  - Tavtigian, Sean
A1  - Bader, Gary D.
A1  - Meindl, Alfons
A1  - Goldgar, David E.
A1  - Andrulis, Irene L.
A1  - Schmutzler, Rita K.
A1  - Easton, Douglas F.
A1  - Schmidt, Marjanka K.
A1  - Hahnen, Eric
A1  - Simard, Jacques
T1  - Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry
JF  - Cancers
N2  - Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
KW  - breast cancer
KW  - genetic susceptibility
KW  - whole-exome sequencing
KW  - moderate-penetrance genes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281768
SN  - 2072-6694
VL  - 14
IS  - 14
ER  - 
TY  - JOUR
A1  - Dörk, Thilo
A1  - Peterlongo, Peter
A1  - Mannermaa, Arto
A1  - Bolla, Manjeet K.
A1  - Wang, Qin
A1  - Dennis, Joe
A1  - Ahearn, Thomas
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Augustinsson, Annelie
A1  - Beane Freeman, Laura E.
A1  - Beckmann, Matthias W.
A1  - Beeghly-Fadiel, Alicia
A1  - Behrens, Sabine
A1  - Bermisheva, Marina
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Burwinkel, Barbara
A1  - Canzian, Federico
A1  - Chan, Tsun L.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Choi, Ji-Yeob
A1  - Christiansen, Hans
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - dos-Santos-Silva, Isabel
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ekici, Arif B.
A1  - Eriksson, Mikael
A1  - Evans, D. Gareth
A1  - Fasching, Peter A.
A1  - Figueroa, Jonine
A1  - Flyger, Henrik
A1  - Fritschi, Lin
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Gao, Chi
A1  - Gapstur, Susan M.
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - Guenél, Pascal
A1  - Haeberle, Lothar
A1  - Haimann, Christopher A.
A1  - Håkansson, Niclas
A1  - Hall, Per
A1  - Hamann, Ute
A1  - Hartman, Mikael
A1  - Hauke, Jan
A1  - Hein, Alexander
A1  - Hillemanns, Peter
A1  - Hogervorst, Frans B. L.
A1  - Hooning, Maartje J.
A1  - Hopper, John L.
A1  - Howell, Tony
A1  - Huo, Dezheng
A1  - Ito, Hidemi
A1  - Iwasaki, Motoki
A1  - Jakubowska, Anna
A1  - Janni, Wolfgang
A1  - John, Esther M.
A1  - Jung, Audrey
A1  - Kaaks, Rudolf
A1  - Kang, Daehee
A1  - Kapoor, Pooja Middha
A1  - Khusnutdinova, Elza
A1  - Kim, Sung-Won
A1  - Kitahara, Cari M.
A1  - Koutros, Stella
A1  - Kraft, Peter
A1  - Kristensen, Vessela N.
A1  - Kwong, Ava
A1  - Lambrechts, Diether
A1  - Le Marchand, Loic
A1  - Li, Jingmei
A1  - Lindström, Sara
A1  - Linet, Martha
A1  - Lo, Wing-Yee
A1  - Long, Jirong
A1  - Lophatananon, Artitaya
A1  - Lubiński, Jan
A1  - Manoochehri, Mehdi
A1  - Manoukian, Siranoush
A1  - Margolin, Sara
A1  - Martinez, Elena
A1  - Matsuo, Keitaro
A1  - Mavroudis, Dimitris
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Milne, Roger L.
A1  - Mohd Taib, Nur Aishah
A1  - Muir, Kenneth
A1  - Mulligan, Anna Marie
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Neven, Patrick
A1  - Newman, William G.
A1  - Offit, Kenneth
A1  - Olopade, Olufunmilayo I.
A1  - Olshan, Andrew F.
A1  - Olson, Janet E.
A1  - Olsson, Håkan
A1  - Park, Sue K.
A1  - Park-Simon, Tjoung-Won
A1  - Peto, Julian
A1  - Plaseska-Karanfilska, Dijana
A1  - Pohl-Rescigno, Esther
A1  - Presneau, Nadege
A1  - Rack, Brigitte
A1  - Radice, Paolo
A1  - Rashid, Muhammad U.
A1  - Rennert, Gad
A1  - Rennert, Hedy S.
A1  - Romero, Atocha
A1  - Ruebner, Matthias
A1  - Saloustros, Emmanouil
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Schneider, Michael O.
A1  - Schoemaker, Minouk J.
A1  - Scott, Christopher
A1  - Shen, Chen-Yang
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Slager, Susan
A1  - Smichkoska, Snezhana
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Stone, Jennifer
A1  - Surowy, Harald
A1  - Swerdlow, Anthony J.
A1  - Tamimi, Rulla M.
A1  - Tapper, William J.
A1  - Teo, Soo H.
A1  - Terry, Mary Beth
A1  - Toland, Amanda E.
A1  - Tollenaar, Rob A. E. M.
A1  - Torres, Diana
A1  - Torres-Mejía, Gabriela
A1  - Troester, Melissa A.
A1  - Truong, Thérèse
A1  - Tsugane, Shoichiro
A1  - Untch, Michael
A1  - Vachon, Celine M.
A1  - van den Ouweland, Ans M. W.
A1  - van Veen, Elke M.
A1  - Vijai, Joseph
A1  - Wendt, Camilla
A1  - Wolk, Alicja
A1  - Yu, Jyh-Cherng
A1  - Zheng, Wei
A1  - Ziogas, Argyrios
A1  - Ziv, Elad
A1  - Dunnig, Alison
A1  - Pharaoh, Paul D. P.
A1  - Schindler, Detlev
A1  - Devilee, Peter
A1  - Easton, Douglas F.
T1  - Two truncating variants in FANCC and breast cancer risk
JF  - Scientific Reports
N2  - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
KW  - oncology
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838
VL  - 9
ER  - 
TY  - JOUR
A1  - Ferreira, Manuel A.
A1  - Gamazon, Eric R.
A1  - Al-Ejeh, Fares
A1  - Aittomäki, Kristiina
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arason, Adalgeir
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Arun, Banu K.
A1  - Asseryanis, Ella
A1  - Azzollini, Jacopo
A1  - Balmaña, Judith
A1  - Barnes, Daniel R.
A1  - Barrowdale, Daniel
A1  - Beckmann, Matthias W.
A1  - Behrens, Sabine
A1  - Benitez, Javier
A1  - Bermisheva, Marina
A1  - Bialkowska, Katarzyna
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Bolla, Manjeet K.
A1  - Borg, Ake
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Broeks, Annegien
A1  - Burwinkel, Barbara
A1  - Caldés, Trinidad
A1  - Caligo, Maria A.
A1  - Campa, Daniele
A1  - Campbell, Ian
A1  - Canzian, Federico
A1  - Carter, Jonathan
A1  - Carter, Brian D.
A1  - Castelao, Jose E.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Christiansen, Hans
A1  - Chung, Wendy K.
A1  - Claes, Kathleen B. M.
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Cox, Angela
A1  - Cross, Simon S.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - de la Hoya, Miguel
A1  - Dennis, Joe
A1  - Devilee, Peter
A1  - Diez, Orland
A1  - Dörk, Thilo
A1  - Dunning, Alison M.
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ejlertsen, Bent
A1  - Ellberg, Carolina
A1  - Engel, Christoph
A1  - Eriksson, Mikael
A1  - Fasching, Peter A.
A1  - Fletcher, Olivia
A1  - Flyger, Henrik
A1  - Friedman, Eitan
A1  - Frost, Debra
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Ganz, Patricia A.
A1  - Gapstur, Susan M.
A1  - Garber, Judy
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Glendon, Gord
A1  - Godwin, Andrew K.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - González-Neira, Anna
A1  - Greene, Mark H.
A1  - Gronwald, Jacek
A1  - Guenél, Pascal
A1  - Haimann, Christopher A.
A1  - Hall, Per
A1  - Hamann, Ute
A1  - He, Wei
A1  - Heyworth, Jane
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hoover, Robert N.
A1  - Hopper, John L.
A1  - Hulick, Peter J.
A1  - Humphreys, Keith
A1  - Imyanitov, Evgeny N.
A1  - Isaacs, Claudine
A1  - Jakimovska, Milena
A1  - Jakubowska, Anna
A1  - James, Paul A.
A1  - Janavicius, Ramunas
A1  - Jankowitz, Rachel C.
A1  - John, Esther M.
A1  - Johnson, Nichola
A1  - Joseph, Vijai
A1  - Karlan, Beth Y.
A1  - Khusnutdinova, Elza
A1  - Kiiski, Johanna I.
A1  - Ko, Yon-Dschun
A1  - Jones, Michael E.
A1  - Konstantopoulou, Irene
A1  - Kristensen, Vessela N.
A1  - Laitman, Yael
A1  - Lambrechts, Diether
A1  - Lazaro, Conxi
A1  - Leslie, Goska
A1  - Lester, Jenny
A1  - Lesueur, Fabienne
A1  - Lindström, Sara
A1  - Long, Jirong
A1  - Loud, Jennifer T.
A1  - Lubiński, Jan
A1  - Makalic, Enes
A1  - Mannermaa, Arto
A1  - Manoochehri, Mehdi
A1  - Margolin, Sara
A1  - Maurer, Tabea
A1  - Mavroudis, Dimitrios
A1  - McGuffog, Lesley
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Michailidou, Kyriaki
A1  - Miller, Austin
A1  - Montagna, Marco
A1  - Moreno, Fernando
A1  - Moserle, Lidia
A1  - Mulligan, Anna Marie
A1  - Nathanson, Katherine L.
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Nevelsteen, Ines
A1  - Nielsen, Finn C.
A1  - Nikitina-Zake, Liene
A1  - Nussbaum, Robert L.
A1  - Offit, Kenneth
A1  - Olah, Edith
A1  - Olopade, Olufunmilayo I.
A1  - Olsson, Håkan
A1  - Osorio, Ana
A1  - Papp, Janos
A1  - Park-Simon, Tjoung-Won
A1  - Parsons, Michael T.
A1  - Pedersen, Inge Sokilde
A1  - Peixoto, Ana
A1  - Peterlongo, Paolo
A1  - Pharaoh, Paul D. P.
A1  - Plaseska-Karanfilska, Dijana
A1  - Poppe, Bruce
A1  - Presneau, Nadege
A1  - Radice, Paolo
A1  - Rantala, Johanna
A1  - Rennert, Gad
A1  - Risch, Harvey A.
A1  - Saloustros, Emmanouil
A1  - Sanden, Kristin
A1  - Sawyer, Elinor J.
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Sharma, Priyanka
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Singer, Christian F.
A1  - Soucy, Penny
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Spurdle, Amanda B.
A1  - Stone, Jennifer
A1  - Swerdlow, Anthony J.
A1  - Tapper, William J.
A1  - Taylor, Jack A.
A1  - Teixeira, Manuel R.
A1  - Terry, Mary Beth
A1  - Teulé, Alex
A1  - Thomassen, Mads
A1  - Thöne, Kathrin
A1  - Thull, Darcy L.
A1  - Tischkowitz, Marc
A1  - Toland, Amanda E.
A1  - Torres, Diana
A1  - Truong, Thérèse
A1  - Tung, Nadine
A1  - Vachon, Celine M.
A1  - van Asperen, Christi J.
A1  - van den Ouweland, Ans M. W.
A1  - van Rensburg, Elizabeth J.
A1  - Vega, Ana
A1  - Viel, Alexandra
A1  - Wang, Qin
A1  - Wappenschmidt, Barbara
A1  - Weitzel, Jeffrey N.
A1  - Wendt, Camilla
A1  - Winqvist, Robert
A1  - Yang, Xiaohong R.
A1  - Yannoukakos, Drakoulis
A1  - Ziogas, Argyrios
A1  - Kraft, Peter
A1  - Antoniou, Antonis C.
A1  - Zheng, Wei
A1  - Easton, Douglas F.
A1  - Milne, Roger L.
A1  - Beesley, Jonathan
A1  - Chenevix-Trench, Georgia
T1  - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
JF  - Nature Communications
N2  - 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.
KW  - cancer
KW  - genetics
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228024
VL  - 10
ER  - 
TY  - JOUR
A1  - Tony, Hans-Peter
A1  - Burmester, Gerd
A1  - Schulze-Koops, Hendrik
A1  - Grunke, Mathias
A1  - Henes, Joerg
A1  - Kötter, Ina
A1  - Haas, Judith
A1  - Unger, Leonore
A1  - Lovric, Svjetlana
A1  - Haubitz, Marion
A1  - Fischer-Betz, Rebecca
A1  - Chehab, Gamal
A1  - Rubbert-Roth, Andrea
A1  - Specker, Christof
A1  - Weinerth, Jutta
A1  - Holle, Julia
A1  - Müller-Ladner, Ulf
A1  - König, Ramona
A1  - Fiehn, Christoph
A1  - Burgwinkel, Philip
A1  - Budde, Klemens
A1  - Sörensen, Helmut
A1  - Meurer, Michael
A1  - Aringer, Martin
A1  - Kieseier, Bernd
A1  - Erfurt-Berge, Cornelia
A1  - Sticherling, Michael
A1  - Veelken, Roland
A1  - Ziemann, Ulf
A1  - Strutz, Frank
A1  - von Wussow, Praxis
A1  - Meier, Florian MP
A1  - Hunzelmann, Nico
A1  - Schmidt, Enno
A1  - Bergner, Raoul
A1  - Schwarting, Andreas
A1  - Eming, Rüdiger
A1  - Schwarz-Eywill, Michael
A1  - Wassenberg, Siegfried
A1  - Fleck, Martin
A1  - Metzler, Claudia
A1  - Zettl, Uwe
A1  - Westphal, Jens
A1  - Heitmann, Stefan
A1  - Herzog, Anna L.
A1  - Wiendl, Heinz
A1  - Jakob, Waltraud
A1  - Schmidt, Elvira
A1  - Freivogel, Klaus
A1  - Dörner, Thomas
A1  - Hertl, Michael
A1  - Stadler, Rudolf
T1  - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)
JF  - Arthritis Research & Therapy
N2  - Introduction: 

Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. 

Methods: 

Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. 

Results: 

A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm)
KW  - GRAID
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856
VL  - 13
IS  - R75
ER  - 
TY  - JOUR
A1  - Zwink, Nadine
A1  - Jenetzky, Ekkehart
A1  - Schmiedeke, Eberhard
A1  - Schmidt, Dominik
A1  - Märzheuser, Schmidt
A1  - Grasshoff-Derr, Sabine
A1  - Holland-Cunz, Stefan
A1  - Weih, Sandra
A1  - Hosie, Stuart
A1  - Reifferscheid, Peter
A1  - Ameis, Helen
A1  - Kujath, Christina
A1  - Rissmann, Anke
A1  - Obermayr, Florian
A1  - Schwarzer, Nicole
A1  - Bartels, Enrika
A1  - Reutter, Heiko
A1  - Brenner, Hermann
T1  - Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study
JF  - Orphanet Journal of Rare Diseases
N2  - Background: The use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
Methods: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births. 
Results: In total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9-12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2-19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6-12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6-12.7) for singletons and 4.9 (2.4-10.1) for multiple births. Conclusions: There is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.
KW  - metaanalysis
KW  - in-vitro fertilization
KW  - reproductive medicine
KW  - anal atresia
KW  - imperforate anus
KW  - anorectal malformation
KW  - birth defects
KW  - prevalence
KW  - assisted reproductive techniques
KW  - congenital malformations
KW  - descriptive epidemiology
KW  - infants born
KW  - children born
KW  - IVF-methods
KW  - technology
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134036
VL  - 7
IS  - 65
ER  - 
TY  - JOUR
A1  - Schoffer, Olaf
A1  - Schülein, Stefanie
A1  - Arand, Gerlinde
A1  - Arnholdt, Hans
A1  - Baaske, Dieter
A1  - Bargou, Ralf C.
A1  - Becker, Nikolaus
A1  - Beckmann, Matthias W.
A1  - Bodack, Yves
A1  - Böhme, Beatrix
A1  - Bozkurt, Tayfun
A1  - Breitsprecher, Regine
A1  - Buchali, Andre
A1  - Burger, Elke
A1  - Burger, Ulrike
A1  - Dommisch, Klaus
A1  - Elsner, Gudrun
A1  - Fernschild, Karin
A1  - Flintzer, Ulrike
A1  - Funke, Uwe
A1  - Gerken, Michael
A1  - Göbel, Hubert
A1  - Grobe, Norbert
A1  - Gumpp, Vera
A1  - Heinzerling, Lucie
A1  - Kempfer, Lana Raffaela
A1  - Kiani, Alexander
A1  - Klinkhammer-Schalke, Monika
A1  - Klöcking, Sabine
A1  - Kreibich, Ute
A1  - Knabner, Katrin
A1  - Kuhn, Peter
A1  - Lutze, Stine
A1  - Mäder, Uwe
A1  - Maisel, Tanja
A1  - Maschke, Jan
A1  - Middeke, Martin
A1  - Neubauer, Andreas
A1  - Niedostatek, Antje
A1  - Opazo-Saez, Anabelle
A1  - Peters, Christoph
A1  - Schell, Beatrice
A1  - Schenkirsch, Gerhard
A1  - Schmalenberg, Harald
A1  - Schmidt, Peter
A1  - Schneider, Constanze
A1  - Schubotz, Birgit
A1  - Seide, Anika
A1  - Strecker, Paul
A1  - Taubenheim, Sabine
A1  - Wackes, Matthias
A1  - Weiß, Steffen
A1  - Welke, Claudia
A1  - Werner, Carmen
A1  - Wittekind, Christian
A1  - Wulff, Jörg
A1  - Zettl, Heike
A1  - Klug, Stefanie J.
T1  - Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011
JF  - BMC Cancer
N2  - Background

Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients.

Methods

Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival.

Results

The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%).

Conclusions

No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.
"
KW  - Malignant melanoma
KW  - TNM staging
KW  - Survival analysis
KW  - Skin cancer screening
KW  - Stage distribution
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164544
VL  - 16
IS  - 936
ER  - 
TY  - JOUR
A1  - Prelog, Martina
A1  - Hilligardt, Deborah
A1  - Schmidt, Christian A.
A1  - Przybylski, Grzegorz K.
A1  - Leierer, Johannes
A1  - Almanzar, Giovanni
A1  - El Hajj, Nady
A1  - Lesch, Klaus-Peter
A1  - Arolt, Volker
A1  - Zwanzger, Peter
A1  - Haaf, Thomas
A1  - Domschke, Katharina
T1  - Hypermethylation of FOXP3 Promoter and Premature Aging of the Immune System in Female Patients with Panic Disorder?
JF  - PLoS ONE
N2  - Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders.
KW  - DNA methylation
KW  - antidepressants
KW  - regulatory T cells
KW  - panic disorder
KW  - treatment guidelines
KW  - telomere length
KW  - inflammatory diseases
KW  - anxiety disorders
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179684
VL  - 11
IS  - 6
ER  - 
TY  - JOUR
A1  - van Loock, Peter
A1  - Alt, Wolfgang
A1  - Becher, Christoph
A1  - Benson, Oliver
A1  - Boche, Holger
A1  - Deppe, Christian
A1  - Eschner, Jürgen
A1  - Höfling, Sven
A1  - Meschede, Dieter
A1  - Michler, Peter
A1  - Schmidt, Frank
A1  - Weinfurter, Harald
T1  - Extending Quantum Links: Modules for Fiber‐ and Memory‐Based Quantum Repeaters
JF  - Advanced Quantum Technologies
N2  - Elementary building blocks for quantum repeaters based on fiber channels and memory stations are analyzed. Implementations are considered for three different physical platforms, for which suitable components are available: quantum dots, trapped atoms and ions, and color centers in diamond. The performances of basic quantum repeater links for these platforms are evaluated and compared, both for present‐day, state‐of‐the‐art experimental parameters as well as for parameters that can in principle be reached in the future. The ultimate goal is to experimentally explore regimes at intermediate distances—up to a few 100 km—in which the repeater‐assisted secret key transmission rates exceed the maximal rate achievable via direct transmission. Two different protocols are considered, one of which is better adapted to the higher source clock rate and lower memory coherence time of the quantum dot platform, while the other circumvents the need of writing photonic quantum states into the memories in a heralded, nondestructive fashion. The elementary building blocks and protocols can be connected in a modular form to construct a quantum repeater system that is potentially scalable to large distances.
KW  - color centers
KW  - quantum communication
KW  - quantum dots
KW  - quantum repeaters
KW  - trapped atoms/ions
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228322
VL  - 3
IS  - 11
ER  -