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1005 Publications visible to you, out of a total of 1005
Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying …g the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population. METHODS To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; P(trend) = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; P(trend) = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers. CONCLUSIONS CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers. IMPACT The combined application of these and other recently identified genetic risk modifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.

Authors: Christoph Engel, Beatrix Versmold, Barbara Wappenschmidt, Jacques Simard, Douglas F. Easton, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Rebecca Mayes, D. Gareth Evans, Rosalind Eeles, Joan Paterson, Carole Brewer, Lesley McGuffog, Antonis C. Antoniou, Dominique Stoppa-Lyonnet, Olga M. Sinilnikova, Laure Barjhoux, Marc Frenay, Cécile Michel, Dominique Leroux, Helene Dreyfus, Christine Toulas, Laurence Gladieff, Nancy Uhrhammer, Yves-Jean Bignon, Alfons Meindl, Norbert Arnold, Raymonda Varon-Mateeva, Dieter Niederacher, Sabine Preisler-Adams, Karin Kast, Helmut Deissler, Christian Sutter, Dorothea Gadzicki, Georgia Chenevix-Trench, Amanda B. Spurdle, Xiaoqing Chen, Jonathan Beesley, Håkan Olsson, Ulf Kristoffersson, Hans Ehrencrona, Annelie Liljegren, Rob B. van der Luijt, Theo A. van Os, Flora E. van Leeuwen, Susan M. Domchek, Timothy R. Rebbeck, Katherine L. Nathanson, Ana Osorio, Teresa Ramón y Cajal, Irene Konstantopoulou, Javier Benítez, Eitan Friedman, Bella Kaufman, Yael Laitman, Phuong L. Mai, Mark H. Greene, Heli Nevanlinna, Kristiina Aittomäki, Csilla I. Szabo, Trinidad Caldes, Fergus J. Couch, Irene L. Andrulis, Andrew K. Godwin, Ute Hamann, Rita K. Schmutzler

Date Published: 8th Nov 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group.
GLA - German Lymphoma Alliance

Abstract (Expand)

To evaluate outcome and prognosis of patients with T-cell lymphoma we analyzed 343 patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Two hundred eighty-nine … patients belonged to 1 of the 4 major T-cell lymphoma subtypes: anaplastic large cell lymphoma (ALCL), anaplastic large cell lymphoma kinase (ALK)-positive (n = 78); ALCL, ALK-negative (n = 113); peripheral T-cell lymphoma, unspecified (PTCLU; n = 70); and angioimmunoblastic T-cell lymphoma (AITL; n = 28). Treatment consisted of 6-8 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone) or etoposide plus (CHOEP). Three-year event-free survival (EFS) and overall survival were 75.8% and 89.8% (ALK-positive ALCL), 50.0% and 67.5% (AITL), 45.7% and 62.1% (ALK-negative ALCL), and 41.1% and 53.9% (PTCLU), respectively. The International Prognostic Index (IPI) was effective in defining risk groups with significantly different outcomes. For patients, </= 60 years with lactate dehydrogenase </= upper normal value (UNV), etoposide improved improved 3-year EFS: 75.4% versus 51.0%, P = .003. In patients > 60 years 6 courses of CHOP administered every 3 weeks remains the standard therapy. Patients with ALK-negative ALCL, PTCLU, or AITL presenting with IPI > 1 have a poor prognosis and should be considered candidates for novel treatment strategies.

Authors: N. Schmitz, L. Trumper, M. Ziepert, M. Nickelsen, A. D. Ho, B. Metzner, N. Peter, M. Loeffler, A. Rosenwald, M. Pfreundschuh

Date Published: 4th Nov 2010

Publication Type: Not specified

Human Diseases: mature T-cell and NK-cell lymphoma

Screening in women at elevated risk for breast cancer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract

Not specified

Authors: Rita Katharina Schmutzler, Christoph Engel, Ingrid Schreer

Date Published: 20th Oct 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed … with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 \times 10^-^9 to P(trend) = 3.9 \times 10^-^7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (P(trend) = 1 \times 10^-^7) to P(trend) = 8 \times 10^-^5; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 \times 10^-^7

Authors: Antonis C. Antoniou, Xianshu Wang, Zachary S. Fredericksen, Lesley McGuffog, Robert Tarrell, Olga M. Sinilnikova, Sue Healey, Jonathan Morrison, Christiana Kartsonaki, Timothy Lesnick, Maya Ghoussaini, Daniel Barrowdale, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Diana Eccles, D. Gareth Evans, Ros Eeles, Louise Izatt, Carol Chu, Fiona Douglas, Joan Paterson, Dominique Stoppa-Lyonnet, Claude Houdayer, Sylvie Mazoyer, Sophie Giraud, Christine Lasset, Audrey Remenieras, Olivier Caron, Agnès Hardouin, Pascaline Berthet, Frans B. L. Hogervorst, Matti A. Rookus, Agnes Jager, Ans van den Ouweland, Nicoline Hoogerbrugge, Rob B. van der Luijt, Hanne Meijers-Heijboer, Encarna B. Gómez García, Peter Devilee, Maaike P. G. Vreeswijk, Jan Lubinski, Anna Jakubowska, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Bohdan Górski, Cezary Cybulski, Amanda B. Spurdle, Helene Holland, David E. Goldgar, Esther M. John, John L. Hopper, Melissa Southey, Saundra S. Buys, Mary B. Daly, Mary-Beth Terry, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Sabine Preisler-Adams, Norbert Arnold, Dieter Niederacher, Christian Sutter, Susan M. Domchek, Katherine L. Nathanson, Timothy Rebbeck, Joanne L. Blum, Marion Piedmonte, Gustavo C. Rodriguez, Katie Wakeley, John F. Boggess, Jack Basil, Stephanie V. Blank, Eitan Friedman, Bella Kaufman, Yael Laitman, Roni Milgrom, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Tomas Kirchhoff, Joseph Vijai, Mia M. Gaudet, David Altshuler, Candace Guiducci, Niklas Loman, Katja Harbst, Johanna Rantala, Hans Ehrencrona, Anne-Marie Gerdes, Mads Thomassen, Lone Sunde, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Alessandra Viel, Paolo Radice, Trinidad Caldes, Miguel de La Hoya, Christian F. Singer, Anneliese Fink-Retter, Mark H. Greene, Phuong L. Mai, Jennifer T. Loud, Lucia Guidugli, Noralane M. Lindor, Thomas v. O. Hansen, Finn C. Nielsen, Ignacio Blanco, Conxi Lazaro, Judy Garber, Susan J. Ramus, Simon A. Gayther, Catherine Phelan, Stephen Narod, Csilla I. Szabo, Javier Benitez, Ana Osorio, Heli Nevanlinna, Tuomas Heikkinen, Maria A. Caligo, Mary S. Beattie, Ute Hamann, Andrew K. Godwin, Marco Montagna, Cinzia Casella, Susan L. Neuhausen, Beth Y. Karlan, Nadine Tung, Amanda E. Toland, Jeffrey Weitzel, Olofunmilayo Olopade, Jacques Simard, Penny Soucy, Wendy S. Rubinstein, Adalgeir Arason, Gad Rennert, Nicholas G. Martin, Grant W. Montgomery, Jenny Chang-Claude, Dieter Flesch-Janys, Hiltrud Brauch, Gianluca Severi, Laura Baglietto, Angela Cox, Simon S. Cross, Penelope Miron, Sue M. Gerty, William Tapper, Drakoulis Yannoukakos, George Fountzilas, Peter A. Fasching, Matthias W. Beckmann, Isabel Dos Santos Silva, Julian Peto, Diether Lambrechts, Robert Paridaens, Thomas Rüdiger, Asta Försti, Robert Winqvist, Katri Pylkäs, Robert B. Diasio, Adam M. Lee, Jeanette Eckel-Passow, Celine Vachon, Fiona Blows, Kristy Driver, Alison Dunning, Paul P. D. Pharoah, Kenneth Offit, V. Shane Pankratz, Hakon Hakonarson, Georgia Chenevix-Trench, Douglas F. Easton, Fergus J. Couch

Date Published: 1st Oct 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Variability of structures in German intensive care units–a representative, nationwide analysis
SepNet - German Competence Network Sepsis

Abstract (Expand)

BACKGROUND Structures in intensive care medicine comprise human as well as material resources, organization, and management and may be related to processes thereby affecting patients’ outcomes. Utilizing …g a unique data base we evaluated structures of German intensive care units (ICUs). METHODS The study was carried out by the German Competence Network Sepsis (SepNet). Data were prospectively collected on a cross-sectional basis in a representative random sample of German hospitals utilizing a questionnaire. Structures were related to ICU outcome of patients with severe sepsis or septic shock. The sample was subdivided in 5 strata according to hospital size. RESULTS A total of 454 ICUs cared for 3877 patients including 415 patients (11%) with severe sepsis or septic shock. The mean number of beds per ICU was 10.4, the ratio of ICU to hospital beds 1:27, both with significant differences depending on hospital size. 81% of the ICUs provided around the clock physician presence (range: 66-98% across hospital strata, p \textless 0.001). Shift-wise, one nurse was responsible for a mean number of 2.7 patients (morning 1:2.3, afternoon 1:2.6, night 1:3.3 patients) with significant variation according to hospital size (smaller hospitals 1:2.9, university hospitals 1:2.1, p \textless 0.001). More than half of all German ICUs are lead by anesthesiologists. Neither physician nor nurse staffing was associated with mortality in the subset of patients with sepsis. CONCLUSIONS In a representative, nationwide sample of German ICUs key elements of structures varied considerably with respect to hospital size. This has to be considered when proposing standards, reimbursement strategies, or quality assessment.

Authors: Jürgen Graf, Andrea Reinhold, Frank M. Brunkhorst, Max Ragaller, Konrad Reinhart, Markus Loeffler, Christoph Engel

Date Published: 1st Oct 2010

Publication Type: Journal article

Human Diseases: disease by infectious agent

WHO grade-specific comparative genomic hybridization pattern of astrocytoma - a meta-analysis
Genetical Statistics and Systems Biology

Abstract (Expand)

To detect novel genetic alterations, many astrocytomas have been investigated by comparative genomic hybridization (CGH). To identify aberration profiles characteristic of World Health Organization … (WHO) grade I, II, III, and IV astrocytoma, we performed a meta-analysis of detailed genome wide CGH data of all 467 cases published so far. After expansion of all given aberrations to the maximum of 850 GTG-band resolution, the frequencies of genetic imbalances were calculated for each chromosomal band, separately for all four WHO grades. Low-grade astrocytoma has already demonstrated one characteristic of glioblastoma multiforme, gain of chromosome 7 with a hot spot at 7q32, but without loss of chromosome 10. In anaplastic astrocytoma, a more complex aberration pattern emerges from diffuse genetic imbalances. Gains of 7q32-q36 and 7p12 become the most frequent aberrations at chromosome 7. In glioblastoma multiforme, coarse aberrations like +7, -9p, -10, and -13 represent the most frequent aberrations as a characteristic pattern. In contrast to lower tumor grades, glioblastoma multiforme demonstrates +7p12 as the most frequently affected band on chromosome 7. To quantify the gradual transition from WHO grade II-IV astrocytoma, we calculated the relative increase and decrease in frequency for each detected aberration of the tumor genome. The most pronounced and diverse changes of genetic material occur at the virtual transition from low-grade to anaplastic astrocytoma. Further transition to glioblastoma multiforme is characterized by gain of 1p, chromosome 7, and loss of chromosome 10. Summing up, the expansion of the CGH results to the 850 GTG-band resolution enabled a meta-analysis to visualize WHO grade-specific aberration profiles in astrocytoma.

Authors: Heidrun Holland, Thomas Koschny, Peter Ahnert, Jürgen Meixensberger, Ronald Koschny

Date Published: 1st Oct 2010

Publication Type: Journal article

Genetic regulation of serum phytosterol levels and risk of coronary artery disease
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnPhytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We … used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD).\backslashr\backslashnMETHODS AND RESULTS\backslashr\backslashnA genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)).\backslashr\backslashnCONCLUSION\backslashr\backslashnCommon variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.

Authors: Daniel Teupser, Ronny Baber, Uta Ceglarek, Markus Scholz, Thomas Illig, Christian Gieger, Lesca Miriam Holdt, Alexander Leichtle, Karin H. Greiser, Dominik Huster, Patrick Linsel-Nitschke, Arne Schäfer, Peter S. Braund, Laurence Tiret, Klaus Stark, Dorette Raaz-Schrauder, Georg M. Fiedler, Wolfgang Wilfert, Frank Beutner, Stephan Gielen, Anika Grosshennig, Inke R. König, Peter Lichtner, Iris M. Heid, Alexander Kluttig, Nour E El Mokhtari, Diana Rubin, Arif B. Ekici, André Reis, Christoph D. Garlichs, Alistair S. Hall, Gert Matthes, Christian Wittekind, Christian Hengstenberg, Francois Cambien, Stefan Schreiber, Karl Werdan, Thomas Meitinger, Markus Loeffler, Nilesh J. Samani, Jeanette Erdmann, Heinz-Erich Wichmann, Heribert Schunkert, Joachim Thiery

Date Published: 1st Aug 2010

Publication Type: Journal article

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