Christoph Engel

About Christoph Engel:
No description specified

LHA ID: 7VYNMKGKWE-1

Location:  Germany

ORCID: https://orcid.org/0000-0002-7247-282X

Joined: 28th Aug 2019

Expertise: hereditary cancer, biometry, epidemiology

Tools: Not specified

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Related items

LIFE - Leipzig Research Center for Civilization Diseases: inactive since

Goal of the Leipzig Research Center for Civilization Diseases (LIFE) is the investigation of civilization diseases like depression, diabetes, allergies or cardiovascular diseases. For this purpose we collect as much data as possible regarding health and living conditions of the population in Leipzig and provide these data for scientists of the University of Leipzig and other research institutions.

Programme: LIFE Management Cluster

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2009

LIFE Adult

This population-based study examined 10,000 participants randomly selected from the Leipzig population (2011 to 2014). A follow-up is to be carried out from 2017 - 2020. The study mainly included people aged between 40 and 79. All participants underwent a 6-hour study program and people over 60 years of age were invited two more times to in-depth study of cognition and depression and the brain (MRI, EEG). Extensive measurements of genome, metabolome and transcriptome are available. The LIFE-ADULT ...

Programme: LIFE Management Cluster

Public web page: http://life.uni-leipzig.de/en/adults/life_adult.html

Start date: 1st Jan 2009

GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

The German Consortium for Hereditary Non-Polyposis Colorectal Cancer has been founded in 1999 by the German Cancer Aid and has been funded by the German Cancer Aid until recently. GC-HNPCC currently comprises 6 university centers providing genetic counseling, histopathological and molecular tissue analysis, genetic testing, and specific structured surveillance programs for early cancer detection at each clinical unit, all based on defined standard operating procedures.

Programme: LIFE Management Cluster

Public web page: https://www.imise.uni-leipzig.de/institut/Projekte/Verbundprojekt-Familiaerer-Darmkrebs

Start date: 1st Jan 1999

GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

The German Consortium for Hereditary Breast and Ovarian Cancer HBOC has been founded in 1996 by the German Cancer Aid and has been funded by the German Cancer Aid until recently. GC-HBOC currently comprises 17 university centers providing genetic counseling, histopathological and molecular tissue analysis, genetic testing, and specific structured surveillance programs for early cancer detection at each clinical unit, all based on defined standard operating procedures.

Programme: LIFE Management Cluster

Public web page: http://www.konsortium-familiaerer-brustkrebs.de/

Start date: 1st Jan 1996

SISPCT
SepNet - German Competence Network Sepsis
No description specified

Submitter: René Hänsel

Studies: SISPCT

Resources: SISPCT Trail Data, SISPCT Trail Metadata

HYPRESS
SepNet - German Competence Network Sepsis
No description specified

Submitter: Christoph Beger

Studies: HYPRESS

Resources: HYPRESS Trial Data, HYPRESS Trial Metadata

HYPRESS
SepNet - German Competence Network Sepsis

Baseline Data and Endpoints for HYPRESS

Submitter: Christoph Beger

Investigation: HYPRESS

Resources: HYPRESS Trial Data, HYPRESS Trial Metadata

Study type: Not specified

SISPCT
SepNet - German Competence Network Sepsis

Baseline Data and Endpoints for SISPCT

Submitter: René Hänsel

Investigation: SISPCT

Resources: SISPCT Trail Data, SISPCT Trail Metadata

Study type: Not specified

SISPCT Trail Metadata
SepNet - German Competence Network Sepsis
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: SISPCT

Study: SISPCT

SISPCT Trail Data
SepNet - German Competence Network Sepsis
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: SISPCT

Study: SISPCT

HYPRESS Trial Data
SepNet - German Competence Network Sepsis

Adjunctive hydrocortisone (HC) therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The case for septic patients without shock remains controversial. We investigated the efficacy of HC in patients with severe sepsis without shock

Restricted Trial Data

Submitter: Christoph Beger

Resource type: Result Dataset of Clinical Study

Technology type: Technology Type

Investigation: HYPRESS

Study: HYPRESS

HYPRESS Trial Metadata
SepNet - German Competence Network Sepsis
No description specified

Submitter: Christoph Beger

Resource type: Result Dataset of Clinical Study

Technology type: Technology Type

Investigation: HYPRESS

Study: HYPRESS

The Leipzig Health Atlas-An Open Platform to Present, Archive, and Share Biomedical Data, Analyses, and Models Online.
LHA - Leipzig Health Atlas

Abstract (Expand)

BACKGROUND: Clinical trials, epidemiological studies, clinical registries, and other prospective research projects, together with patient care services, are main sources of data in the medical research … domain. They serve often as a basis for secondary research in evidence-based medicine, prediction models for disease, and its progression. This data are often neither sufficiently described nor accessible. Related models are often not accessible as a functional program tool for interested users from the health care and biomedical domains. OBJECTIVE: The interdisciplinary project Leipzig Health Atlas (LHA) was developed to close this gap. LHA is an online platform that serves as a sustainable archive providing medical data, metadata, models, and novel phenotypes from clinical trials, epidemiological studies, and other medical research projects. METHODS: Data, models, and phenotypes are described by semantically rich metadata. The platform prefers to share data and models presented in original publications but is also open for nonpublished data. LHA provides and associates unique permanent identifiers for each dataset and model. Hence, the platform can be used to share prepared, quality-assured datasets and models while they are referenced in publications. All managed data, models, and phenotypes in LHA follow the FAIR principles, with public availability or restricted access for specific user groups. RESULTS: The LHA platform is in productive mode (https://www.health-atlas.de/). It is already used by a variety of clinical trial and research groups and is becoming increasingly popular also in the biomedical community. LHA is an integral part of the forthcoming initiative building a national research data infrastructure for health in Germany.

Authors: T. Kirsten, F. A. Meineke, H. Loeffler-Wirth, C. Beger, A. Uciteli, S. Staubert, M. Lobe, R. Hansel, F. G. Rauscher, J. Schuster, T. Peschel, H. Herre, J. Wagner, S. Zachariae, C. Engel, M. Scholz, E. Rahm, H. Binder, M. Loeffler

Date Published: 3rd Aug 2022

Publication Type: Journal article

The Human Blood Transcriptome in a Large Population Cohort and Its Relation to Aging and Health.
LIFE Adult, oBIG - omics Bioinformatics for Health

Abstract (Expand)

Background: The blood transcriptome is expected to provide a detailed picture of an organism's physiological state with potential outcomes for applications in medical diagnostics and molecular and … epidemiological research. We here present the analysis of blood specimens of 3,388 adult individuals, together with phenotype characteristics such as disease history, medication status, lifestyle factors, and body mass index (BMI). The size and heterogeneity of this data challenges analytics in terms of dimension reduction, knowledge mining, feature extraction, and data integration. Methods: Self-organizing maps (SOM)-machine learning was applied to study transcriptional states on a population-wide scale. This method permits a detailed description and visualization of the molecular heterogeneity of transcriptomes and of their association with different phenotypic features. Results: The diversity of transcriptomes is described by personalized SOM-portraits, which specify the samples in terms of modules of co-expressed genes of different functional context. We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. We find a striking overlap of signatures shared by multiple diseases, aging, and obesity driven by an underlying common pattern, which was associated with the immune response and the increase of inflammatory processes. Conclusions: Machine learning applications for large and heterogeneous omics data provide a holistic view on the diversity of the human blood transcriptome. It provides a tool for comparative analyses of transcriptional signatures and of associated phenotypes in population studies and medical applications.

Authors: M. Schmidt, L. Hopp, A. Arakelyan, H. Kirsten, C. Engel, K. Wirkner, K. Krohn, R. Burkhardt, J. Thiery, M. Loeffler, H. Loeffler-Wirth, H. Binder

Date Published: 11th Mar 2021

Publication Type: Journal article

Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect …t but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. METHODS A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. RESULTS There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. CONCLUSION We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

Authors: Nasim Mavaddat, Antonis C. Antoniou, Thea M. Mooij, Maartje J. Hooning, Bernadette A. Heemskerk-Gerritsen, Catherine Noguès, Marion Gauthier-Villars, Olivier Caron, Paul Gesta, Pascal Pujol, Alain Lortholary, Daniel Barrowdale, Debra Frost, D. Gareth Evans, Louise Izatt, Julian Adlard, Ros Eeles, Carole Brewer, Marc Tischkowitz, Alex Henderson, Jackie Cook, Diana Eccles, Klaartje van Engelen, Marian J. E. Mourits, Margreet G. E. M. Ausems, Linetta B. Koppert, John L. Hopper, Esther M. John, Wendy K. Chung, Irene L. Andrulis, Mary B. Daly, Saundra S. Buys, Javier Benitez, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Flora E. van Leeuwen, Brita Arver, Håkan Olsson, Rita K. Schmutzler, Christoph Engel, Karin Kast, Kelly-Anne Phillips, Mary Beth Terry, Roger L. Milne, David E. Goldgar, Matti A. Rookus, Nadine Andrieu, Douglas F. Easton

Date Published: 1st Dec 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract

After publication of the original article [1], we were notified that columns in Table 2 were erroneously displayed.

Authors: Nasim Mavaddat, Antonis C. Antoniou, Thea M. Mooij, Maartje J. Hooning, Bernadette A. Heemskerk-Gerritsen, Catherine Noguès, Marion Gauthier-Villars, Olivier Caron, Paul Gesta, Pascal Pujol, Alain Lortholary, Daniel Barrowdale, Debra Frost, D. Gareth Evans, Louise Izatt, Julian Adlard, Ros Eeles, Carole Brewer, Marc Tischkowitz, Alex Henderson, Jackie Cook, Diana Eccles, Klaartje van Engelen, Marian J. E. Mourits, Margreet G. E. M. Ausems, Linetta B. Koppert, John L. Hopper, Esther M. John, Wendy K. Chung, Irene L. Andrulis, Mary B. Daly, Saundra S. Buys, Javier Benitez, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Flora E. van Leeuwen, Brita Arver, Håkan Olsson, Rita K. Schmutzler, Christoph Engel, Karin Kast, Kelly-Anne Phillips, Mary Beth Terry, Roger L. Milne, David E. Goldgar, Matti A. Rookus, Nadine Andrieu, Douglas F. Easton

Date Published: 1st Dec 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Norms of Interocular Circumpapillary Retinal Nerve Fiber Layer Thickness Differences at 768 Retinal Locations
LIFE Adult

Abstract (Expand)

Purpose: The onset and progression of optic neuropathies like glaucoma often occurs asymmetrically between the two eyes of a patient. Interocular circumpapillary retinal nerve fiber layer thickness … (cpRNFLT) differences could detect disease earlier. To apply such differences diagnostically, detailed location specific norms are necessary. Methods: Spectral-domain optical coherence tomography cpRNFLT circle scans from the population-based Leipzig Research Centre for Civilization Diseases–Adult study were selected. At each of the 768 radial scanning locations, normative interocular cpRNFLT difference distributions were calculated based on age and interocular radius difference. Results: A total of 8966 cpRNFLT scans of healthy eyes (4483 patients; 55% female; age range, 20–79 years) were selected. Global cpRNFLT average was 1.53 µm thicker in right eyes (P < 2.2 × 10–16). On 96% of the 768 locations, left minus right eye differences were significant (P < 0.05), varying between +11.6 µm (superonasal location) and −11.8 µm (nasal location). Increased age and difference in interocular scanning radii were associated with an increased mean and variance of interocular cpRNFLT difference at most retinal locations, apart from the area temporal to the inferior RNF bundle where cpRNFLT becomes more similar between eyes with age. Conclusions: We provide pointwise normative distributions of interocular cpRNFLT differences at an unprecedentedly high spatial resolution of 768 A-scans and reveal considerable location specific asymmetries as well as their associations with age and scanning radius differences between eyes. Translational Relevance: To facilitate clinical application, we implement these age- and radius-specific norms across all 768 locations in an open-source software to generate patient-specific normative color plots.

Authors: Neda Baniasadi, Franziska G. Rauscher, Dian Li, Mengyu Wang, Eun Young Choi, Hui Wang, Thomas Peschel, Kerstin Wirkner, Toralf Kirsten, Joachim Thiery, Christoph Engel, Markus Loeffler, Tobias Elze

Date Published: 3rd Aug 2020

Publication Type: Journal article

Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Importance The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection …n and risk reduction in this population. Objective To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. Design, Setting, and Participants Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Results Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P \textless .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P \textless .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P \textless .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P \textless .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier. Conclusions and Relevance Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.

Authors: Valentina Silvestri, Goska Leslie, Daniel R. Barnes, Bjarni A. Agnarsson, Kristiina Aittomäki, Elisa Alducci, Irene L. Andrulis, Rosa B. Barkardottir, Alicia Barroso, Daniel Barrowdale, Javier Benitez, Bernardo Bonanni, Ake Borg, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Carlo Capalbo, Ian Campbell, Wendy K. Chung, Kathleen B. M. Claes, Sarah V. Colonna, Laura Cortesi, Fergus J. Couch, Miguel de La Hoya, Orland Diez, Yuan Chun Ding, Susan Domchek, Douglas F. Easton, Bent Ejlertsen, Christoph Engel, D. Gareth Evans, Lidia Feliubadalò, Lenka Foretova, Florentia Fostira, Lajos Géczi, Anne-Marie Gerdes, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Eric Hahnen, Frans B. L. Hogervorst, John L. Hopper, Peter J. Hulick, Claudine Isaacs, Angel Izquierdo, Paul A. James, Ramunas Janavicius, Uffe Birk Jensen, Esther M. John, Vijai Joseph, Irene Konstantopoulou, Allison W. Kurian, Ava Kwong, Elisabetta Landucci, Fabienne Lesueur, Jennifer T. Loud, Eva Machackova, Phuong L. Mai, Keivan Majidzadeh-A, Siranoush Manoukian, Marco Montagna, Lidia Moserle, Anna Marie Mulligan, Katherine L. Nathanson, Heli Nevanlinna, Joanne Ngeow Yuen Ye, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Laura Papi, Sue K. Park, Inge Sokilde Pedersen, Pedro Perez-Segura, Annabeth H. Petersen, Pedro Pinto, Berardino Porfirio, Miquel Angel Pujana, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Barak Rosenzweig, Maria Rossing, Marta Santamariña, Rita K. Schmutzler, Leigha Senter, Jacques Simard, Christian F. Singer, Angela R. Solano, Melissa C. Southey, Linda Steele, Zoe Steinsnyder, Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R. Teixeira, Soo H. Teo, Mary Beth Terry, Mads Thomassen, Amanda E. Toland, Sara Torres-Esquius, Nadine Tung, Christi J. van Asperen, Ana Vega, Alessandra Viel, Jeroen Vierstraete, Barbara Wappenschmidt, Jeffrey N. Weitzel, Greet Wieme, Sook-Yee Yoon, Kristin K. Zorn, Lesley McGuffog, Michael T. Parsons, Ute Hamann, Mark H. Greene, Judy A. Kirk, Susan L. Neuhausen, Timothy R. Rebbeck, Marc Tischkowitz, Georgia Chenevix-Trench, Antonis C. Antoniou, Eitan Friedman, Laura Ottini

Date Published: 2nd Jul 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but … analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

Authors: Helian Feng, Alexander Gusev, Bogdan Pasaniuc, Lang Wu, Jirong Long, Zomoroda Abu-Full, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Adalgeir Arason, Volker Arndt, Kristan J. Aronson, Banu K. Arun, Ella Asseryanis, Paul L. Auer, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel R. Barnes, Daniel Barrowdale, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska, Ana Blanco, Carl Blomqvist, Bram Boeckx, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Sander Canisius, Daniele Campa, Brian D. Carter, Jonathan Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Hans Christiansen, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, Fergus J. Couch, Angela Cox, Simon S. Cross, Cezary Cybulski, Kamila Czene, Mary B. Daly, Miguel de La Hoya, Kim de Leeneer, Joe Dennis, Peter Devilee, Orland Diez, Susan M. Domchek, Thilo Dörk, Isabel Dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Bent Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Christopher Hake, Wei He, Jane Heyworth, Frans B. L. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Guanmengqian Huang, Peter J. Hulick, Keith Humphreys, Evgeny N. Imyanitov, Claudine Isaacs, Milena Jakimovska, Anna Jakubowska, Paul James, Ramunas Janavicius, Rachel C. Jankowitz, Esther M. John, Nichola Johnson, Vijai Joseph, Audrey Jung, Beth Y. Karlan, Elza Khusnutdinova, Johanna I. Kiiski, Irene Konstantopoulou, Vessela N. Kristensen, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Dominique Leroux, Goska Leslie, Jenny Lester, Fabienne Lesueur, Noralane Lindor, Sara Lindström, Wing-Yee Lo, Jennifer T. Loud, Jan Lubiński, Enes Makalic, Arto Mannermaa, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, John W. M. Martens, Maria E. Martinez, Laura Matricardi, Tabea Maurer, Dimitrios Mavroudis, Lesley McGuffog, Alfons Meindl, Usha Menon, Kyriaki Michailidou, Pooja M. Kapoor, Austin Miller, Marco Montagna, Fernando Moreno, Lidia Moserle, Anna M. Mulligan, Taru A. Muranen, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Finn C. Nielsen, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Håkan Olsson, Ana Osorio, Janos Papp, Tjoung-Won Park-Simon, Michael T. Parsons, Inge S. Pedersen, Ana Peixoto, Paolo Peterlongo, Julian Peto, Paul D. P. Pharoah, Kelly-Anne Phillips, Dijana Plaseska-Karanfilska, Bruce Poppe, Nisha Pradhan, Karolina Prajzendanc, Nadege Presneau, Kevin Punie, Katri Pylkäs, Paolo Radice, Johanna Rantala, Muhammad Usman Rashid, Gad Rennert, Harvey A. Risch, Mark Robson, Atocha Romero, Emmanouil Saloustros, Dale P. Sandler, Catarina Santos, Elinor J. Sawyer, Marjanka K. Schmidt, Daniel F. Schmidt, Rita K. Schmutzler, Minouk J. Schoemaker, Rodney J. Scott, Priyanka Sharma, Xiao-Ou Shu, Jacques Simard, Christian F. Singer, Anne-Bine Skytte, Penny Soucy, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Jennifer Stone, Anthony J. Swerdlow, William J. Tapper, Jack A. Taylor, Manuel R. Teixeira, Mary Beth Terry, Alex Teulé, Mads Thomassen, Kathrin Thöne, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Rob A. E. M. Tollenaar, Diana Torres, Thérèse Truong, Nadine Tung, Celine M. Vachon, Christi J. van Asperen, Ans M. W. van den Ouweland, Elizabeth J. van Rensburg, Ana Vega, Alessandra Viel, Paula Vieiro-Balo, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Roger L. Milne, Douglas F. Easton, Georgia Chenevix-Trench, Wei Zheng, Peter Kraft, Xia Jiang

Date Published: 1st Jul 2020

Publication Type: Journal article

Human Diseases: breast cancer

Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline …e PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 \times 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 \times 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 \times 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 \times 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 \times 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

Authors: Xin Yang, Goska Leslie, Alicja Doroszuk, Sandra Schneider, Jamie Allen, Brennan Decker, Alison M. Dunning, James Redman, James Scarth, Inga Plaskocinska, Craig Luccarini, Mitul Shah, Karen Pooley, Leila Dorling, Andrew Lee, Muriel A. Adank, Julian Adlard, Kristiina Aittomäki, Irene L. Andrulis, Peter Ang, Julian Barwell, Jonine L. Bernstein, Kristie Bobolis, Åke Borg, Carl Blomqvist, Kathleen B. M. Claes, Patrick Concannon, Adeline Cuggia, Julie O. Culver, Francesca Damiola, Antoine de Pauw, Orland Diez, Jill S. Dolinsky, Susan M. Domchek, Christoph Engel, D. Gareth Evans, Florentia Fostira, Judy Garber, Lisa Golmard, Ellen L. Goode, Stephen B. Gruber, Eric Hahnen, Christopher Hake, Tuomas Heikkinen, Judith E. Hurley, Ramunas Janavicius, Zdenek Kleibl, Petra Kleiblova, Irene Konstantopoulou, Anders Kvist, Holly Laduca, Ann S. G. Lee, Fabienne Lesueur, Eamonn R. Maher, Arto Mannermaa, Siranoush Manoukian, Rachel McFarland, Wendy McKinnon, Alfons Meindl, Kelly Metcalfe, Nur Aishah Mohd Taib, Jukka Moilanen, Katherine L. Nathanson, Susan Neuhausen, Pei Sze Ng, Tu Nguyen-Dumont, Sarah M. Nielsen, Florian Obermair, Kenneth Offit, Olufunmilayo I. Olopade, Laura Ottini, Judith Penkert, Katri Pylkäs, Paolo Radice, Susan J. Ramus, Vilius Rudaitis, Lucy Side, Rachel Silva-Smith, Valentina Silvestri, Anne-Bine Skytte, Thomas Slavin, Jana Soukupova, Carlo Tondini, Alison H. Trainer, Gary Unzeitig, Lydia Usha, Thomas van Overeem Hansen, James Whitworth, Marie Wood, Cheng Har Yip, Sook-Yee Yoon, Amal Yussuf, George Zogopoulos, David Goldgar, John L. Hopper, Georgia Chenevix-Trench, Paul Pharoah, Sophia H. L. George, Judith Balmaña, Claude Houdayer, Paul James, Zaki El-Haffaf, Hans Ehrencrona, Marketa Janatova, Paolo Peterlongo, Heli Nevanlinna, Rita Schmutzler, Soo-Hwang Teo, Mark Robson, Tuya Pal, Fergus Couch, Jeffrey N. Weitzel, Aaron Elliott, Melissa Southey, Robert Winqvist, Douglas F. Easton, William D. Foulkes, Antonis C. Antoniou, Marc Tischkowitz

Date Published: 1st Mar 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non-Insulin-Treated Type 2 Diabetes
Genetical Statistics and Systems Biology

Abstract (Expand)

CONTEXT Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type …e 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. OBJECTIVES AND DESIGN Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. RESULTS In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non-insulin-treated diabetes (OR 1.37; P = 0.002). CONCLUSIONS Genetic variation in the HLA class II locus exerts risk and protective effects on non-insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.

Authors: Thomas Jacobi, Lucas Massier, Nora Klöting, Katrin Horn, Alexander Schuch, Peter Ahnert, Christoph Engel, Markus Löffler, Ralph Burkhardt, Joachim Thiery, Anke Tönjes, Michael Stumvoll, Matthias Blüher, Ilias Doxiadis, Markus Scholz, Peter Kovacs

Date Published: 1st Mar 2020

Publication Type: Journal article

Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. METHODS We … We analysed data from 6178 families, 125 with pathogenic variants in RAD51C; and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families, while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. RESULTS Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C RR = 7.55, 95%CI:5.60-10.19, p = 5 \times 10-40; RAD51D RR = 7.60, 95%CI:5.61-10.30, p = 5 \times 10-39) and BC (RAD51C RR = 1.99, 95%CI:1.39-2.85, p = 1.55 \times 10-4; RAD51D RR = 1.83, 95%CI:1.24-2.72, p = 0.002). For both RAD51C and RAD51D, there was a suggestion that the TOC RRs increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 were 11% (95%CI:6-21%) for RAD51C and 13% (95%CI:7-23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 were 21% (95%CI:15-29%) for RAD51C and 20% (95%CI:14-28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C/D pathogenic variant carriers varied by cancer family history, and could be as high as 32-36% for TOC, for carriers with two first degree relatives diagnosed with TOC; or 44-46% for BC, for carriers with two first degree relatives diagnosed with BC. CONCLUSIONS These estimates will facilitate the genetic counselling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models.

Authors: Xin Yang, Honglin Song, Goska Leslie, Christoph Engel, Eric Hahnen, Bernd Auber, Judit Horváth, Karin Kast, Dieter Niederacher, Clare Turnbull, Richard Houlston, Helen Hanson, Chey Loveday, Jill S. Dolinsky, Holly Laduca, Susan J. Ramus, Usha Menon, Adam N. Rosenthal, Ian Jacobs, Simon A. Gayther, Ed Dicks, Heli Nevanlinna, Kristiina Aittomäki, Liisa M. Pelttari, Hans Ehrencrona, Åke Borg, Anders Kvist, Barbara Rivera, Thomas v. O. Hansen, Malene Djursby, Andrew Lee, Joe Dennis, David D. Bowtell, Nadia Traficante, Orland Diez, Judith Balmaña, Stephen B. Gruber, Georgia Chenevix-Trench, Allan Jensen, Susanne K. Kjær, Estrid Høgdall, Laurent Castéra, Judy Garber, Ramunas Janavicius, Ana Osorio, Lisa Golmard, Ana Vega, Fergus J. Couch, Mark Robson, Jacek Gronwald, Susan M. Domchek, Julie O. Culver, Miguel de La Hoya, Douglas F. Easton, William D. Foulkes, Marc Tischkowitz, Alfons Meindl, Rita K. Schmutzler, Paul D. P. Pharoah, Antonis C. Antoniou

Date Published: 28th Feb 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Associations of Sex Hormones and Anthropometry with the Speaking Voice Profile in the Adult General Population
LIFE Adult

The goal of this study was to investigate to what extent body mass index (BMI), body height, body weight, breast-to-abdomen-ratio, testosterone, estradiol, dehydroepiandrosterone-sulfate (DHEA-S), folliclestimulating hormone, and luteinizing hormone are associated with the sound pressure level and the fundamental frequency of the speaking voice in a cross-sectional approach among adults in the general population.

Data for Publication: Jost L, et al; J Voice. 2017 Jul 21. pii: S0892-1997(17)30216-3. ...

Creators: Christoph Engel, Christoph Engel

Submitter: René Hänsel

Data file type: Clinical Data

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Life Mental demand trial data
LIFE Adult

trial data for the mental demandVariableMeaning Gender0=female1=maleMarital Status0 = married, living with partner1 = married and living separated, single, divorced, widowedEducation1 = low2 = medium3 = highEver_diabetes/ heart attack0 = no1 = yesDepression0 = no1 = yes

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: Not specified

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Prevalence of moderately increased albuminuria among individuals with normal HbA1c level but impaired glucose tolerance: Results from the LIFE-Adult-Study
LIFE Adult

A total of 2695 individuals (age 40-79 years, 48% men) without prior diagnosis of diabetes and complete measurement of HbA1c, FPG, 2 h-PG and urine albumin-creatinine ratio (UACR) were taken from a large population-based epidemiological study in the City of Leipzig, Germany.

Diabetes screening strategies using glycated haemoglobin (HbA1c) as first-instance diagnostic parameter may cause failure to detect individuals with abnormal glucose regulation and possible signs of microvascular complications ...

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: Clinical Data

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Olfactory function is associated with cognitive performance: results from the population-based LIFE-Adult-Study.
LIFE Adult

Cognitive assessments comprised tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD): verbal fluency (VF), word list learning and recall (WLL, WLR), and the Trail Making Tests (TMT) A and B. The "Sniffin' Sticks Screening 12" test was used to measure olfactory performance. Linear regression analyses were performed to determine associations between the number of correctly identified odors (0 to 12) and the five cognitive test scores, adjusted for sex, age, education, ...

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: Clinical Data

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SISPCT-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: ODM Data

SISPCT
SepNet - German Competence Network Sepsis
No description specified

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: Clinical Data

SISPCT-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: Clinical Data

GC-HBOC database explorer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

A dataset with information on cancer history, mutation status and surveillance history for more than 100 000 study patients is provided in i2b2 (Informatics for Integrating Biology and the Bedside, http://www.i2b2.org/software). Members of the German Consortium for Hereditary Breast and Ovarian Cancer can request access to i2b2 and will be able to perform database queries independently, e.g. with regard to identify suitable patient populations for scientific evaluation projects.

Creators: Christoph Engel, Silke Zachariae

Submitter: René Hänsel

Data file type: Clinical Data

Human Diseases: hereditary breast ovarian cancer syndrome

External Link
SISPCT Metadata-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: ODM Data

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SISPCT Metadata
SepNet - German Competence Network Sepsis
No description specified

Creator: Christoph Engel

Submitter: René Hänsel

Data file type: Clinical Data

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Future 10-year risk calculator
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

The 'Future 10-year risk calculator' is a tool designed to help determine the optimal timing for follow-up counseling based on the cumulative breast cancer risks provided in the CanRisk-Report created by the CanRisk website as a result of the BOADICEA risk assessment. It is not a replacement for the BOADICEA model, nor is it intended for medical diagnosis, treatment decisions, or the monitoring of health conditions. The risk estimation assumes that the individual's and family's risk profile remains ...

Creators: Christoph Engel, Silke Zachariae

Submitter: Silke Zachariae

MMRpredict
GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

Depending on the calculated mutation probability genetic counsellors can decide whether patients should undergo further analysis of microsatellite instability and immunohistochemistry. The model is recommended for patients with an age at colorectal cancer diagnosis of 55 or younger.

"MMRpredict" is a risk prediction model for patients with colorectal cancer (Barnetson et al. 2006). It calculates the risk of having a mutation in the mismatch repair genes MLH1, MSH2 and MSH6 (overall probability) ...

Creators: Christoph Engel, Silke Zachariae

Submitter: Silke Zachariae

PREMM1,2,6
GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

The PREMM1,2,6 has been developed as a pretest to decide whether patients suspected of having Lynch syndrome should be tested for germline mismatch repair gene mutations. "PREMM1,2,6" is a logistic regression model. It calculates the risk of having a mutation in the mismatch repair genes MLH1, MSH2 and MSH6 (for single genes and overall) based on the personal and familial cancer history of the proband (colorectal, endometrial, and other Lynch syndrome related cancers).

Creators: Silke Zachariae, Christoph Engel, Kastrinos et al.

Submitter: Silke Zachariae

Manchester Scoring System
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Motivation: The "Manchester Scoring System" can be used to assist clinicians and genetic counselors in the clinical management of families suspected of having hereditary breast and ovarian cancer and to decide whether genetic testing should be performed.

Description: The "Manchester Scoring System" is an empirical mutation risk prediction model. In its current form, a risk score for the identification of a pathogenic BRCA1/2 mutation is being calculated based on the number of breast and ovarian ...

Creators: Christoph Engel, Silke Zachariae, Evans, D.G. et al. (2009)

Submitter: Silke Zachariae

GC-HBOC BC Risk Explorer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

The GC-HBOC BC Risk Explorer (GC-HBOC BC-RE) predicts the breast cancer risk for BRCA1/2 carriers and high-risk non-carriers at risk for first breast cancer (cohort 1), and BRCA1/2 carriers and high-risk non-carriers who were previously diagnosed with unilateral breast cancer, and are at risk for contralateral breast cancer (cohort 2). GC-HBOC BC-RE is based on data from female BRCA1/2 carriers and non-carriers with a family history of breast and ovarian cancer, who participated in the intensified ...

Creators: Christoph Engel, Silke Zachariae

Submitter: Silke Zachariae

Claus
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Motivation: The eClaus model can be used to calculate mutation risks for BRCA1/2 as well as life-time risks for breast cancer in women from families with multiple and/or early onset cases of breast and ovarian cancer. The model can be used to assist genetic counselors in clinical decision making regarding genetic testing, intensified surveillance, and prophylatic surgery.

Description: The Claus model is a genetic breast cancer risk calculation model assuming a single rare, highly penetrant gene. ...

Creators: Christoph Engel, Silke Zachariae, Claus, E.B. et al. (1991 and 1994)

Submitter: Silke Zachariae

PREMM5
GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

The PREMM5 has been developed as a pretest to decide whether patients suspected of having Lynch syndrome should be tested for germline mismatch repair gene mutations. In contrast to "PREMM1,2,6" it can be used to predict mutation probabilities in unaffected index patients. "PREMM5" is a logistic regression model. It calculates the risk of having a mutation in the mismatch repair genes MLH1, MSH2/EPCAM, MSH6 and PMS2 (for single genes and overall) based on the personal and familial cancer history ...

Creators: Silke Zachariae, Christoph Engel, Kastrinos et al.

Submitter: Silke Zachariae

GC-HBOC Mutation Frequency Explorer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Motivation: The "GC-HBOC Mutation Frequency Explorer" can be used to assist clinicians and genetic counselors in the clinical management of families suspected of having hereditary breast and ovarian cancer and to decide whether genetic testing should be performed.

Description: The "GC-HBOC Mutation Frequency Explorer" is a tool to determine the observed frequencies of pathogenic BRCA1 and BRCA2 mutations based on familial cancer history data collected since 1996 by the German Consortium for ...

Creators: Christoph Engel, Silke Zachariae

Submitter: Silke Zachariae

External Link
Prevalence of moderately increased albuminuria among individuals with normal HbA1c level but impaired glucose tolerance: Results from the LIFE-Adult-Study
LIFE Adult

Diabetes screening strategies using glycated haemoglobin (HbA1c) as first-instance diagnostic parameter may cause failure to detect individuals with abnormal glucose regulation and possible signs of microvascular complications despite “rule-out” HbA1c levels. This cross-sectional study examined the diagnostic performance of HbA1c in relation to fasting and two-hour postload plasma glucose (FPG/2 h-PG), and investigated whether individuals with normal HbA1c but abnormal FPG/2 h-PG have a higher ...

Creator: Christoph Engel

Submitter: René Hänsel

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