Search

Your search keyword '"Zachariae, Silke"' showing total 47 results
Start Over Author "Zachariae, Silke"
47 results on '"Zachariae, Silke"'

1. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Author

Win, Aung Ko, Dowty, James G., Reece, Jeanette C., Lee, Grant, Templeton, Allyson S., Plazzer, John-Paul, Buchanan, Daniel D., Akagi, Kiwamu, Aksoy, Seçil, Alonso, Angel, Alvarez, Karin, Amor, David J., Ankathil, Ravindran, Aretz, Stefan, Arnold, Julie L., Aronson, Melyssa, Austin, Rachel, Backman, Ann-Sofie, Bajwa-ten Broeke, Sanne W., Barca-Tierno, Verónica, Barwell, Julian, Bernstein, Inge, Berthet, Pascaline, Betz, Beate, Bignon, Yves-Jean, Boisjoli, Talya, Bonadona, Valérie, Briollais, Laurent, Brunet, Joan, Bucksch, Karolin, Buecher, Bruno, Buettner, Reinhard, Burn, John, Caldés, Trinidad, Capella, Gabriel, Caron, Olivier, Casey, Graham, Chew, Min H., Choi, Yun-hee, Church, James, Clendenning, Mark, Colas, Chrystelle, Cops, Elisa J., Coupier, Isabelle, Cruz-Correa, Marcia, de la Chapelle, Albert, de Wind, Niels, Dębniak, Tadeusz, Della Valle, Adriana, Delnatte, Capuccine, Dhooge, Marion, Dominguez-Valentin, Mev, Drouet, Youenn, Duijkers, Floor A., Engel, Christoph, Esperon, Patricia, Evans, D. Gareth, Falcón de Vargas, Aída, Figueiredo, Jane C, Foulkes, William, Fourme, Emmanuelle, Frebourg, Thierry, Gallinger, Steven, Garre, Pilar, Genuardi, Maurizio, Gerdes, Anne-Marie, Gima, Lauren M., Giraud, Sophie, Goodwin, Annabel, Görgens, Heike, Green, Kate, Guillem, Jose, Guillén-Ponce, Carmen, Guimbaud, Roselyne, Guindalini, Rodrigo S.C., Half, Elizabeth E., Hall, Michael J, Hampel, Heather, Hansen, Thomas V.O., Heinimann, Karl, Hes, Frederik J., Hill, James, Ho, Judy W.C., Holinski-Feder, Elke, Hoogerbrugge, Nicoline, Hüneburg, Robert, Huntley, Vanessa, James, Paul A., Jensen, Uffe B, John, Thomas, Juhari, Wan K.W., Kalady, Matthew, Kastrinos, Fay, Kloor, Matthias, Kohonen-Corish, Maija RJ, Krogh, Lotte N., Kupfer, Sonia S., Ladabaum, Uri, Lagerstedt-Robinson, Kristina, Lalloo, Fiona, Lasset, Christine, Latchford, Andrew, Laurent-Puig, Pierre, Lautrup, Charlotte K., Leggett, Barbara A., Lejeune, Sophie, LeMarchand, Loic, Ligtenberg, Marjolijn, Lindor, Noralane, Loeffler, Markus, Longy, Michel, Lopez, Francisco, Lowery, Jan, Lubiński, Jan, Lucassen, Anneke M, Lynch, Patrick M., Malińska, Karolina, Matsubara, Nagahide, Mecklin, Jukka-Pekka, Møller, Pål, Monahan, Kevin, Morrison, Patrick J., Nattermann, Jacob, Navarro, Matilde, Neffa, Florencia, Neklason, Deborah, Newcomb, Polly A., Ngeow, Joanne, Nichols, Cassandra, Nielsen, Maartje, Nixon, Dawn M., Nogues, Catherine, Okkels, Henrik, Olschwang, Sylviane, Pachter, Nicholas, Pai, Rish K., Palmero, Edenir I., Pande, Mala, Parry, Susan, Patel, Swati G., Pearlman, Rachel, Perne, Claudia, Pineda, Marta, Poplawski, Nicola K, Pylvänäinen, Kirsi, Qiu, Jay, Rahner, Nils, Ramesar, Raj, Rasmussen, Lene J., Redler, Silke, Reis, Rui M., Ricciardiello, Luigi, Rogoża-Janiszewska, Emilia, Rosty, Christophe, Samadder, N. Jewel, Sampson, Julian R., Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Schuster, Helène, Scott, Rodney, Senter, Leigha, Seppälä, Toni T, Shtoyerman, Rakefet, Sijmons, Rolf H., Snyder, Carrie, Solomon, Ilana B., Soto, Jose Luis, Southey, Melissa C., Spigelman, Allan, Spirandelli, Florencia, Spurdle, Amanda B., Steinke-Lange, Verena, Stoffel, Elena M., Strassburg, Christian P., Sunde, Lone, Susman, Rachel, Syngal, Sapna, Tanakaya, Kohji, Tezcan, Gülçin, Therkildsen, Christina, Thibodeau, Steve, Tomita, Naohiro, Tucker, Katherine M., Tunca, Berrin, Turchetti, Daniela, Uhrhammer, Nancy, Utsunomiya, Joji, Vaccaro, Carlos, van Duijnhoven, Fränzel J.B., van Wanzeele, Meghan J., Vangala, Deepak B., Vasen, Hans F.A., von Knebel Doeberitz, Magnus, von Salomé, Jenny, Wadt, Karin A.W., Ward, Robyn L., Weitz, Jürgen, Weitzel, Jeffrey N., Williams, Heinric, Winship, Ingrid, Wise, Paul E., Wods, Julie, Woods, Michael O., Yamaguchi, Tatsuro, Zachariae, Silke, Zahary, Mohd N., Hopper, John L., Haile, Robert W., Macrae, Finlay A., Möslein, Gabriela, and Jenkins, Mark A.

Published
2021
Full Text
View/download PDF

3. No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies

Author

Engel, Christoph, Vasen, Hans F., Seppälä, Toni, Aretz, Stefan, Bigirwamungu-Bargeman, Marloes, de Boer, Sybrand Y., Bucksch, Karolin, Büttner, Reinhard, Holinski-Feder, Elke, Holzapfel, Stefanie, Hüneburg, Robert, Jacobs, Maarten A.J.M., Järvinen, Heikki, Kloor, Matthias, von Knebel Doeberitz, Magnus, Koornstra, Jan J., van Kouwen, Mariette, Langers, Alexandra M., van de Meeberg, Paul C., Morak, Monika, Möslein, Gabriela, Nagengast, Fokko M., Pylvänäinen, Kirsi, Rahner, Nils, Renkonen-Sinisalo, Laura, Sanduleanu, Silvia, Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Steinke-Lange, Verena, Strassburg, Christian P., Vecht, Juda, Verhulst, Marie-Louise, de Vos tot Nederveen Cappel, Wouter, Zachariae, Silke, Mecklin, Jukka-Pekka, and Loeffler, Markus

Published
2018
Full Text
View/download PDF

4. Connecting chronic stress and anxiety: a multi-dimensional perspective.

Author

Hussenoeder, Felix S., Conrad, Ines, Pabst, Alexander, Engel, Christoph, Zachariae, Silke, Zeynalova, Samira, Yahiaoui-Doktor, Maryam, Glaesmer, Heide, Hinz, Andreas, Witte, Veronika, Wichmann, Gunnar, Kirsten, Toralf, Löffler, Markus, Villringer, Arno, and Riedel-Heller, Steffi G.

Subjects
RESEARCH, PERSONALITY, SOCIAL support, CHRONIC diseases, JOB stress, PUBLIC health, RISK assessment, PSYCHOLOGICAL tests, SOCIAL isolation, RESEARCH funding, EMPLOYEES' workload, ANXIETY, STATISTICAL correlation, SOCIODEMOGRAPHIC factors, WORRY, PSYCHOLOGICAL stress, DISEASE complications
Abstract

Studies show a connection between anxiety and stress, but with little differentiation between different domains of stress. In this article, we utilize a multi-dimensional approach to better understand the relationship between different chronic stress domains and anxiety. This will allow researchers to identify and address those areas of stress that are most relevant with regard to anxiety. We used data from a sub sample of the LIFE-Adult-Study (n = 1085) to analyze the association between nine different areas of chronic stress (Trier Inventory for Chronic Stress, TICS) and anxiety (General Anxiety Disorder 7, GAD-7), controlling for sociodemographic variables, personality, and social support. There was a significant and positive association between Work Overload, Pressure to Perform, Social Tensions, Social Isolation, Chronic Worrying, and anxiety. After including the control variables, only Work Overload and Chronic Worrying remained significant. By focusing on Work Overload and Chronic Worrying researchers, practitioners, and policy makers can help to mitigate anxiety and related health problems in the population in an efficient way. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

6. Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer

Author

Rhiem, Kerstin, Zachariae, Silke, Waha, Anke, Grill, Sabine, Hester, Anna, Golatta, Michael; https://orcid.org/0000-0002-2605-0060, van Mackelenbergh, Marion, Fehm, Tanja, Schlaiß, Tanja, Ripperger, Tim; https://orcid.org/0000-0001-6470-8612, Ledig, Susanne, Meisel, Cornelia, Speiser, Dorothee; https://orcid.org/0000-0002-6447-629X, Veselinovic, Kristina, Schröder, Christopher, Witzel, Isabell; https://orcid.org/0000-0002-8734-4521, Gallwas, Julia, Weber, Bernhard H F; https://orcid.org/0000-0002-8808-7723, Solbach, Christine; https://orcid.org/0000-0001-8284-3199, Aktas, Bariyhe, Hahnen, Eric, Engel, Christoph; https://orcid.org/0000-0002-7247-282X, Schmutzler, Rita, Rhiem, Kerstin, Zachariae, Silke, Waha, Anke, Grill, Sabine, Hester, Anna, Golatta, Michael; https://orcid.org/0000-0002-2605-0060, van Mackelenbergh, Marion, Fehm, Tanja, Schlaiß, Tanja, Ripperger, Tim; https://orcid.org/0000-0001-6470-8612, Ledig, Susanne, Meisel, Cornelia, Speiser, Dorothee; https://orcid.org/0000-0002-6447-629X, Veselinovic, Kristina, Schröder, Christopher, Witzel, Isabell; https://orcid.org/0000-0002-8734-4521, Gallwas, Julia, Weber, Bernhard H F; https://orcid.org/0000-0002-8808-7723, Solbach, Christine; https://orcid.org/0000-0001-8284-3199, Aktas, Bariyhe, Hahnen, Eric, Engel, Christoph; https://orcid.org/0000-0002-7247-282X, and Schmutzler, Rita

Abstract

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2, and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and Methods: In 1,600 women with sTNBC (median age at diagnosis: 41 years, range 19–78 years), we investigated the association between age at diagnosis and PV occurrence in cancer predisposition genes using logistic regression. Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes (BRCA1: n = 170 [10.6%]; BRCA2: n = 46 [2.9%], other: n = 44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years (n = 194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95% confidence interval: 1.21–1.65; p < 0.001). The PV prevalence predicted by the model was above 10% for diagnoses before the age of 56.8 years. Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still uncertain estimate for women with sTNBC diagnosed above the age of 60 years, further studies are needed.

Published
2023

7. Physical activity and mental health: the connection between step count and depression, anxiety and quality of sleep.

Author

Hussenoeder, Felix S., Conrad, Ines, Pabst, Alexander, Engel, Christoph, Zachariae, Silke, Zeynalova, Samira, Glaesmer, Heide, Hinz, Andreas, Witte, Veronica, Schomerus, Georg, Löffler, Markus, Villringer, Arno, Sander, Christian, and Riedel-Heller, Steffi G.

Subjects
MENTAL illness risk factors, SLEEP quality, PERSONALITY, WEARABLE technology, REGRESSION analysis, RISK assessment, PHYSICAL activity, SOCIOECONOMIC factors, PSYCHOLOGICAL tests, MENTAL depression, DESCRIPTIVE statistics, CENTER for Epidemiologic Studies Depression Scale, ANXIETY, DATA analysis software, MARITAL status, SECONDARY analysis
Abstract

While there are studies connecting everyday physical activity (PA) to mental health, they mostly use self-report measures for PA which are biased in multiple ways. Nevertheless, a realistic assessment of everyday PA is important for the development and implementation of low-threshold public health interventions. Therefore, we want to analyze the relationship between objectively measured daily steps and mental health. We included 1451 subjects from a subsample of the population-based LIFE-Adult-Study (2011–2014) with an average age of 55.0 years, 52.1% were female. We analyzed the effects of PA (step count measured via SenseWear Pro 3) on depression (CES-D), anxiety (GAD-7), and quality of sleep (PSQI). The regression analysis showed a significant negative association between low to moderate PA [Incidence rate ratio: 0.87 (0.77; 0.98)] as well as high to very high PA [0.84 (0.74; 0.95)] and depression and no significant associations between PA and anxiety [l-m: 0.98 (0.81; 1.18)/h-vh: 1.00 (0.82; 1.21)] or quality of sleep [l-m: 0.94 (0.84, 1.06)/h-vh: 0.92 (0.82, 1.03)], controlling for sociodemographic variables and personality. Low-threshold interventions that increase daily step count could be a useful approach for the prevention of depression. The use of objective PA measurement for research is highly encouraged. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

8. Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer

Author

Rhiem, Kerstin, primary, Zachariae, Silke, additional, Waha, Anke, additional, Grill, Sabine, additional, Hester, Anna, additional, Golatta, Michael, additional, van Mackelenbergh, Marion, additional, Fehm, Tanja, additional, Schlaiß, Tanja, additional, Ripperger, Tim, additional, Ledig, Susanne, additional, Meisel, Cornelia, additional, Speiser, Dorothee, additional, Veselinovic, Kristina, additional, Schröder, Christopher, additional, Witzel, Isabell, additional, Gallwas, Julia, additional, Weber, Bernhard H.F., additional, Solbach, Christine, additional, Aktas, Bariyhe, additional, Hahnen, Eric, additional, Engel, Christoph, additional, and Schmutzler, Rita, additional

Published
2023
Full Text
View/download PDF

9. Physical activity and mental health: the connection between step count and depression, anxiety and quality of sleep

Author

Hussenoeder, Felix S., primary, Conrad, Ines, additional, Pabst, Alexander, additional, Engel, Christoph, additional, Zachariae, Silke, additional, Zeynalova, Samira, additional, Glaesmer, Heide, additional, Hinz, Andreas, additional, Witte, Veronica, additional, Schomerus, Georg, additional, Löffler, Markus, additional, Villringer, Arno, additional, Sander, Christian, additional, and Riedel-Heller, Steffi G., additional

Published
2022
Full Text
View/download PDF

10. HerediCaRe: Dokumentations- und IT-Lösung eines spezialisierten Registers für erblichen Brust- und Eierstockkrebs

Author

Engel, Christoph, additional, Wieland, Kerstin, additional, Zachariae, Silke, additional, Bucksch, Karolin, additional, Enders, Ute, additional, Schoenwiese, Ulrike, additional, Yahiaoui-Doktor, Maryam, additional, Keupp, Katharina, additional, Waha, Anke, additional, Hahnen, Eric, additional, Remy, Robert, additional, Ernst, Corinna, additional, Loeffler, Markus, additional, and Schmutzler, Rita K., additional

Published
2022
Full Text
View/download PDF

11. Connecting chronic stress and anxiety: a multi-dimensional perspective

Author

Hussenoeder, Felix S., primary, Conrad, Ines, additional, Pabst, Alexander, additional, Engel, Christoph, additional, Zachariae, Silke, additional, Zeynalova, Samira, additional, Yahiaoui-Doktor, Maryam, additional, Glaesmer, Heide, additional, Hinz, Andreas, additional, Witte, Veronika, additional, Wichmann, Gunnar, additional, Kirsten, Toralf, additional, Löffler, Markus, additional, Villringer, Arno, additional, and Riedel-Heller, Steffi G., additional

Published
2022
Full Text
View/download PDF

12. Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Author

Engel, Christoph, Rhiem, Kerstin, Hahnen, Eric, Loibl, Sibylle, Weber, Karsten E., Seiler, Sabine, Zachariae, Silke, Hauke, Jan, Wappenschmidt, Barbara, Waha, Anke, Blümcke, Britta, Kiechle, Marion, Meindl, Alfons, Niederacher, Dieter, Bartram, Claus R., Speiser, Dorothee, Schlegelberger, Brigitte, Arnold, Norbert, Wieacker, Peter, Leinert, Elena, Gehrig, Andrea, Briest, Susanne, Kast, Karin, Riess, Olaf, Emons, Günter, Weber, Bernhard H. F., Engel, Jutta, Schmutzler, Rita K., and on behalf of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC)

Published
2018
Full Text
View/download PDF

13. Different Areas of Chronic Stress and Their Associations with Depression

Author

Hussenoeder, Felix S., primary, Conrad, Ines, additional, Pabst, Alexander, additional, Luppa, Melanie, additional, Stein, Janine, additional, Engel, Christoph, additional, Zachariae, Silke, additional, Zeynalova, Samira, additional, Yahiaoui-Doktor, Maryam, additional, Glaesmer, Heide, additional, Hinz, Andreas, additional, Witte, Veronica, additional, Wichmann, Gunnar, additional, Kirsten, Toralf, additional, Löffler, Markus, additional, Villringer, Arno, additional, and Riedel-Heller, Steffi G., additional

Published
2022
Full Text
View/download PDF

14. Adenoma and colorectal cancer risks in Lynch syndrome, Lynch-like syndrome and familial colorectal cancer type X

Author

Bucksch, Karolin, Zachariae, Silke, Ahadova, Aysel, Aretz, Stefan, Buttner, Reinhard, Goergens, Heike, Holinski-Feder, Elke, Hueneburg, Robert, Kloor, Matthias, Doeberitz, Magnus Knebel, Ladigan-Badura, Swetlana, Moeslein, Gabriela, Morak, Monika, Nattermann, Jacob, Perne, Claudia, Redler, Silke, Schmetz, Ariane, Steinke-Lange, Verena, Surowy, Harald, Vangala, Deepak B., Weitz, Juergen, Loeffler, Markus, Engel, Christoph, Bucksch, Karolin, Zachariae, Silke, Ahadova, Aysel, Aretz, Stefan, Buttner, Reinhard, Goergens, Heike, Holinski-Feder, Elke, Hueneburg, Robert, Kloor, Matthias, Doeberitz, Magnus Knebel, Ladigan-Badura, Swetlana, Moeslein, Gabriela, Morak, Monika, Nattermann, Jacob, Perne, Claudia, Redler, Silke, Schmetz, Ariane, Steinke-Lange, Verena, Surowy, Harald, Vangala, Deepak B., Weitz, Juergen, Loeffler, Markus, and Engel, Christoph

Abstract

Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk-adapted surveillance policies in LS, LLS and FCCX.

Published
2022

16. HerediCaRe: Dokumentations- und IT-Lösung eines spezialisierten Registers für erblichen Brust- und Eierstockkrebs

Author

Engel, Christoph, primary, Wieland, Kerstin, primary, Zachariae, Silke, additional, Bucksch, Karolin, additional, Enders, Ute, additional, Schoenwiese, Ulrike, additional, Yahiaoui-Doktor, Maryam, additional, Keupp, Katharina, additional, Waha, Anke, additional, Hahnen, Eric, additional, Remy, Robert, additional, Ernst, Corinna, additional, Loeffler, Markus, additional, and Schmutzler, Rita K., additional

Published
2021
Full Text
View/download PDF

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

Author

Kirsten, Toralf, Meineke, Frank A., Loeffler-Wirth, Henry, Beger, Christoph, Uciteli, Alexandr, Stäubert, Sebastian, Löbe, Matthias, Hänsel, René, Rauscher, Franziska G., Schuster, Judith, Peschel, Thomas, Herre, Heinrich, Wagner, Jonas, Zachariae, Silke, Engel, Christoph, Scholz, Markus, Rahm, Erhard, Binder, Hans, and Loeffler, Markus

Abstract

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 (). 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. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

19. Variation in the Risk of Colorectal Cancer for Lynch Syndrome: A retrospective family cohort study

Author

Win, Aung Ko, Dowty, James G., Reece, Jeanette C., Lee, Grant, Templeton, Allyson S., Plazzer, John-Paul, Buchanan, Daniel D., Akagi, Kiwamu, Aksoy, Seçil, Alonso, Angel, Alvarez, Karin, Amor, David J., Ankathil, Ravindran, Aretz, Stefan, Arnold, Julie L., Aronson, Melyssa, Austin, Rachel, Backman, Ann-Sofie, Bajwa–ten Broeke, Sanne W., Barca-Tierno, Verónica, Barwell, Julian, Bernstein, Inge, Berthet, Pascaline, Betz, Beate, Bignon, Yves-Jean, Boisjoli, Talya, Bonadona, Valérie, Briollais, Laurent, Brunet, Joan, Bucksch, Karolin, Buecher, Bruno, Buettner, Reinhard, Burn, John, Caldés, Trinidad, Capella, Gabriel, Caron, Olivier, Casey, Graham, Chew, Min H., Choi, Yun-hee, Church, James, Clendenning, Mark, Colas, Chrystelle, Cops, Elisa J., Coupier, Isabelle, Cruz-Correa, Marcia, de la Chapelle, Albert, de Wind, Niels, Dębniak, Tadeusz, Della Valle, Adriana, Delnatte, Capuccine, Dhooge, Marion, Dominguez-Valentin, Mev, Drouet, Youenn, Duijkers, Floor A., Engel, Christoph, Esperon, Patricia, Evans, D. Gareth, de Vargas, Aída Falcón, Figueiredo, Jane C, Foulkes, William, Fourme, Emmanuelle, Frebourg, Thierry, Gallinger, Steven, Garre, Pilar, Genuardi, Maurizio, Gerdes, Anne-Marie, Gima, Lauren M., Giraud, Sophie, Goodwin, Annabel, Görgens, Heike, Green, Kate, Guillem, Jose, Guillén-Ponce, Carmen, Guimbaud, Roselyne, Guindalini, Rodrigo S. C., Half, Elizabeth E., Hall, Michael J, Hampel, Heather, Hansen, Thomas V. O., Heinimann, Karl, Hes, Frederik J., Hill, James, Ho, Judy W.C., Holinski-Feder, Elke, Hoogerbrugge, Nicoline, Hüneburg, Robert, Huntley, Vanessa, James, Paul A., Jensen, Uffe B, John, Thomas, Juhari, Wan K.W., Kalady, Matthew, Kastrinos, Fay, Kloor, Matthias, Kohonen-Corish, Maija RJ, Krogh, Lotte N., Kupfer, Sonia S., Ladabaum, Uri, Lagerstedt-Robinson, Kristina, Lalloo, Fiona, Lasset, Christine, Latchford, Andrew, Laurent-Puig, Pierre, Lautrup, Charlotte K., Leggett, Barbara A., Lejeune, Sophie, LeMarchand, Loic, Ligtenberg, Marjolijn, Lindor, Noralane, Loeffler, Markus, Longy, Michel, Lopez, Francisco, Lowery, Jan, Lubiński, Jan, Lucassen, Anneke M, Lynch, Patrick M., Malińska, Karolina, Matsubara, Nagahide, Mecklin, Jukka-Pekka, Møller, Pål, Monahan, Kevin, Morrison, Patrick J., Nattermann, Jacob, Navarro, Matilde, Neffa, Florencia, Neklason, Deborah, Newcomb, Polly A., Ngeow, Joanne, Nichols, Cassandra, Nielsen, Maartje, Nixon, Dawn M., Nogues, Catherine, Okkels, Henrik, Olschwang, Sylviane, Pachter, Nicholas, Pai, Rish K., Palmero, Edenir I., Pande, Mala, Parry, Susan, Patel, Swati G., Pearlman, Rachel, Perne, Claudia, Pineda, Marta, Poplawski, Nicola K, Pylvänäinen, Kirsi, Qiu, Jay, Rahner, Nils, Ramesar, Raj, Rasmussen, Lene J., Redler, Silke, Reis, Rui M., Ricciardiello, Luigi, Rogoża-Janiszewska, Emilia, Rosty, Christophe, Samadder, N. Jewel, Sampson, Julian R., Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Schuster, Helène, Scott, Rodney, Senter, Leigha, Seppälä, Toni T, Shtoyerman, Rakefet, Sijmons, Rolf H., Snyder, Carrie, Solomon, Ilana B., Soto, Jose Luis, Southey, Melissa C., Spigelman, Allan, Spirandelli, Florencia, Spurdle, Amanda B., Steinke-Lange, Verena, Stoffel, Elena M., Strassburg, Christian P., Sunde, Lone, Susman, Rachel, Syngal, Sapna, Tanakaya, Kohji, Tezcan, Gülçin, Therkildsen, Christina, Thibodeau, Steve, Tomita, Naohiro, Tucker, Katherine M., Tunca, Berrin, Turchetti, Daniela, Uhrhammer, Nancy, Utsunomiya, Joji, Vaccaro, Carlos, van Duijnhoven, Fränzel J.B., van Wanzeele, Meghan J., Vangala, Deepak B., Vasen, Hans F.A., von Knebel Doeberitz, Magnus, von Salomé, Jenny, Wadt, Karin A. W., Ward, Robyn L., Weitz, Jürgen, Weitzel, Jeffrey N., Williams, Heinric, Winship, Ingrid, Wise, Paul E., Wods, Julie, Woods, Michael O., Yamaguchi, Tatsuro, Zachariae, Silke, Zahary, Mohd N., Hopper, John L., Haile, Robert W., Macrae, Finlay A., Möslein, Gabriela, and Jenkins, Mark A.

Subjects
Article
Abstract

BACKGROUND: Current clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the average age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate how much penetrance varies between carriers of pathogenic variants in the same gene by sex and continent of residence of the carrier. METHODS: We studied 79,809 relatives from 5,255 families, of at least three relatives, in which at least one was a confirmed carrier of a pathogenic or likely pathogenic variant in a mismatch repair gene (1,829 MLH1, 2,179 MSH2, 798 MSH6, 449 PMS2), recruited in 15 countries from North America, Europe and Australasia by the collaborative centres of the International Mismatch Repair Consortium. We used modified segregation analysis conditioned on ascertainment to estimate the average penetrance and modelled unmeasured polygenic factors to estimate the variation in penetrance of colorectal cancer. The existence of familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested using a Wald p-value for the null hypothesis that the polygenic standard deviation is zero. FINDINGS: There was strong evidence of the existence of familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was more prominent for MLH1 and MSH2 variant carriers; depending on gene, sex, and continent, with 7–56% of carriers having a risk of colorectal cancer to age 80 of less than 20%, and 9–44% having a risk of more than 80%, while only 10–19% had a risk of 40–60%. INTERPRETATION: Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessment for precision prevention and early detection of colorectal cancer for Lynch syndrome.

Published
2021

21. HerediCaRe: Documentation and IT Solution of a Specialized Registry for Hereditary Breast and Ovarian Cancer

Author

Engel, Christoph, Wieland, Kerstin, Zachariae, Silke, Bucksch, Karolin, Enders, Ute, Schoenwiese, Ulrike, Yahiaoui-Doktor, Maryam, Keupp, Katharina, Waha, Anke, Hahnen, Eric, Remy, Robert, Ernst, Corinna, Loeffler, Markus, Schmutzler, Rita K., Engel, Christoph, Wieland, Kerstin, Zachariae, Silke, Bucksch, Karolin, Enders, Ute, Schoenwiese, Ulrike, Yahiaoui-Doktor, Maryam, Keupp, Katharina, Waha, Anke, Hahnen, Eric, Remy, Robert, Ernst, Corinna, Loeffler, Markus, and Schmutzler, Rita K.

Abstract

Zusammenfassung Das nationale Register HerediCaRe fur die Evaluation und Verbesserung der risiko-adjustierten Pravention bei erblichem Brust- und Eierstockkrebs ist eines von sechs vom BMBF geforderten modellhaften Registern in der Versorgungsforschung. In diesem Beitrag beschreiben und diskutieren wir die zur standardisierten Datenerfassung gewahlte Dokumentations- und IT-Losung auf der Basis der zuvor definierten speziellen funktionalen Anforderungen. Die Dokumentation gliedert sich in verschiedene patientenindividuell einzusetzende Module, die auf einem zuvor festgelegten Merkmalskatalog beruhen. Aufgrund spezieller funktionaler Anforderungen wurde eine eigene Datenerfassungsanwendung auf der Basis von ORACLE und ORACLE Forms entwickelt und implementiert. Die speziellen Anforderungen umfassten u.a. die Einbindung grafischer Stammbaumdarstellungen, den strukturierten Upload von Stammbaumdaten und molekulargenetischen Informationen, die automatisierte Altdatenubernahme aus dem Vorgangersystem, sowie die freie Programmierbarkeit von beliebig komplexen Datenbankabfragen zur zentralen Datenqualitatsprufung. In die Anwendung ist eine Datenbank zur patienten-unabhangigen Verwaltung genetischer Risikovarianten nahtlos integriert und mit den patientenbezogenen Daten verknupft. Die Vor- und Nachteile der gewahlten IT-Losung werden kritisch diskutiert. Insgesamt kommen wir zu der Schlussfolgerung, dass es angesichts der komplexen Dokumentation und der speziellen Funktionsanforderungen alternativ keine fertigen Softwareprodukte zu der von uns gewahlten Eigenentwicklung existieren. Abstract The national registry HerediCaRe for the evaluation and improvement of risk-adjusted prevention in hereditary breast and ovarian cancer is one of six model registries in health services research funded by the BMBF. In this paper, we describe and discuss the documentation and IT solution chosen for standardized data collection based on the specific functional requirements previously defined

Published
2021

22. Depressive symptomatology in early retirees associated with reason for retirement: Results from the population-based LIFE-adult-study

Author

Zuelke, Andrea E., Roehr, Susanne, Schroeter, Matthias L., Witte, A. Veronica, Hinz, Andreas, Glaesmer, Heide, Engel, Christoph, Enzenbach, Cornelia, Zachariae, Silke, Zeynalova, Samira, Loeffler, Markus, Villringer, Arno, and Riedel-Heller, Steffi G.

Subjects
Psychiatry, Psychiatry and Mental health, depressive symptoms, population-based study, Center for Epidemiologic Studies Depression Scale, early retirement, pension, mental health, Original Research
Abstract

Background: Transition from employment to retirement is regarded a crucial event. However, there is mixed evidence on associations between retirement and mental health, especially regarding early retirement. In Germany, cases of early retirement due to ill health—particularly, mental ill health—are increasing. Therefore, we investigated the association between early retirement and depressive symptoms, including information on different types of early retirement.Methods: We analyzed data from 4,808 participants of the population-based LIFE-Adult-Study (age: 40–65 years, 654 retired, 4,154 employed), controlling for sociodemographic information, social network, pre-existing health conditions, and duration of retirement. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Regression analysis using entropy balancing was applied to achieve covariate balance between retired and employed subjects.Results: We found no overall-differences in depressive symptoms between employed and retired persons (men: b = −.52; p = 0.431; women: b = .05; p = .950). When looking at different types of early retirement, ill-health retirement was linked to increased depressive symptoms in women (b = 4.68, 95% CI = 1.71; 7.65), while voluntary retirement was associated with reduced depressive symptoms in men (b= −1.83, 95% CI = −3.22; −.43) even after controlling for covariates. For women, statutory retirement was linked to lower depressive symptomatology (b = −2.00, 95% CI = −3.99; −.02).Conclusion: Depressive symptomatology among early retirees depends on reason for retirement: For women, ill-health retirement is linked to higher levels of depressive symptoms. Women who retire early due to ill-health constitute a risk group for depressive symptoms that needs specific attention in the health care and social security system.

Published
2020

23. Additional file 1 of Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study

Author

Bucksch, Karolin, Zachariae, Silke, Aretz, Stefan, Büttner, Reinhard, Holinski-Feder, Elke, Holzapfel, Stefanie, Hüneburg, Robert, Kloor, Matthias, Doeberitz, Magnus Von Knebel, Morak, Monika, Möslein, Gabriela, Nattermann, Jacob, Perne, Claudia, Rahner, Nils, Schmiegel, Wolff, Schulmann, Karsten, Steinke-Lange, Verena, Strassburg, Christian P., Vangala, Deepak B., Weitz, Jürgen, Loeffler, Markus, and Engel, Christoph

Abstract

Additional file 1 Table S1. Characteristics of female patients. Table S2. Characteristics of male patients. Table S3. Number of patients, observation times (person-years) and number of incident cancers. Table S4. Types of incident cancers considered as “any cancer”. Table S5. Cumulative cancer risks (%) by age for female patients. Table S6. Cumulative cancer risks (%) by age for male patients. Figure S7. Age-dependent cumulative cancer risks by risk group and sex. Figure S8. Age-dependent cumulative cancer risks of LS patients by gene and sex. Figure S9. Comparison with general population risks: standardised incidence ratios (SIRs) with 95% confidence interval for female patients. Figure S10. Comparison with general population risks: standardised incidence ratios (SIRs) with 95% confidence interval for male patients.

Published
2020
Full Text
View/download PDF

24. Breast cancer risk inBRCA1/2mutation carriers and noncarriers under prospective intensified surveillance

Author

Engel, Christoph, Fischer, Christine, Zachariae, Silke, Bucksch, Karolin, Rhiem, Kerstin, Giesecke, Jutta, Herold, Natalie, Wappenschmidt, Barbara, Huebbel, Verena, Maringa, Monika, Reichstein-Gnielinski, Simone, Hahnen, Eric, Bartram, Claus R., Dikow, Nicola, Schott, Sarah, Speiser, Dorothee, Horn, Denise, Fallenberg, Eva M., Kiechle, Marion, Quante, Anne S., Vesper, Anne-Sophie, Fehm, Tanja, Mundhenke, Christoph, Arnold, Norbert, Leinert, Elena, Just, Walter, Siebers-Renelt, Ulrike, Weigel, Stefanie, Gehrig, Andrea, Woeckel, Achim, Schlegelberger, Brigitte, Pertschy, Stefanie, Kast, Karin, Wimberger, Pauline, Briest, Susanne, Loeffler, Markus, Bick, Ulrich, Schmutzler, Rita K., Engel, Christoph, Fischer, Christine, Zachariae, Silke, Bucksch, Karolin, Rhiem, Kerstin, Giesecke, Jutta, Herold, Natalie, Wappenschmidt, Barbara, Huebbel, Verena, Maringa, Monika, Reichstein-Gnielinski, Simone, Hahnen, Eric, Bartram, Claus R., Dikow, Nicola, Schott, Sarah, Speiser, Dorothee, Horn, Denise, Fallenberg, Eva M., Kiechle, Marion, Quante, Anne S., Vesper, Anne-Sophie, Fehm, Tanja, Mundhenke, Christoph, Arnold, Norbert, Leinert, Elena, Just, Walter, Siebers-Renelt, Ulrike, Weigel, Stefanie, Gehrig, Andrea, Woeckel, Achim, Schlegelberger, Brigitte, Pertschy, Stefanie, Kast, Karin, Wimberger, Pauline, Briest, Susanne, Loeffler, Markus, Bick, Ulrich, and Schmutzler, Rita K.

Abstract

Comparably little is known about breast cancer (BC) risks in women from families tested negative forBRCA1/2mutations despite an indicative family history, as opposed toBRCA1/2mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers ofBRCA1/2mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n= 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n= 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) forBRCA1mutation carriers, 43.2% (95% CI 32.1-56.3%) forBRCA2mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) forBRCA1mutation carriers, 13.5 (95% CI 9.2-19.1) forBRCA2mutation carriers and 4.9 (95% CI 3.8-6.3) forBRCA1/2noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) forBRCA1mutation carriers, 6.6% (95% CI 3.4-12.5%) forBRCA2mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women fromBRCA1/2negative families with elevated risk.

Published
2020

25. Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome

Author

Engel, Christoph, Ahadova, Aysel, Seppala, Toni T., Aretz, Stefan, Bigirwamungu-Bargeman, Marloes, Blaeker, Hendrik, Bucksch, Karolin, Buettner, Reinhard, Cappel, Wouter T. De Vos Tot Nederveen, Endris, Volker, Holinski-Feder, Elke, Holzapfel, Stefanie, Hueneburg, Robert, Jacobs, Maarten A. J. M., Koornstra, Jan J., Langers, Alexandra M., Lepisto, Anna, Morak, Monika, Moeslein, Gabriela, Peltomaeki, Paivi, Pylvaenaeinen, Kirsi, Rahner, Nils, Renkonen-Sinisalo, Laura, Schulmann, Karsten, Steinke-Lange, Verena, Stenzinger, Albrecht, Strassburg, Christian P., van de Meeberg, Paul C., van Kouwen, Mariette, van Leerdam, Monique, Vangala, Deepak B., Vecht, Juda, Verhulst, Marie-Louise, Doeberitz, Magnus von Knebel, Weitz, Juergen, Zachariae, Silke, Loeffler, Markus, Mecklin, Jukka-Pekka, Kloor, Matthias, Vasen, Hans F., Engel, Christoph, Ahadova, Aysel, Seppala, Toni T., Aretz, Stefan, Bigirwamungu-Bargeman, Marloes, Blaeker, Hendrik, Bucksch, Karolin, Buettner, Reinhard, Cappel, Wouter T. De Vos Tot Nederveen, Endris, Volker, Holinski-Feder, Elke, Holzapfel, Stefanie, Hueneburg, Robert, Jacobs, Maarten A. J. M., Koornstra, Jan J., Langers, Alexandra M., Lepisto, Anna, Morak, Monika, Moeslein, Gabriela, Peltomaeki, Paivi, Pylvaenaeinen, Kirsi, Rahner, Nils, Renkonen-Sinisalo, Laura, Schulmann, Karsten, Steinke-Lange, Verena, Stenzinger, Albrecht, Strassburg, Christian P., van de Meeberg, Paul C., van Kouwen, Mariette, van Leerdam, Monique, Vangala, Deepak B., Vecht, Juda, Verhulst, Marie-Louise, Doeberitz, Magnus von Knebel, Weitz, Juergen, Zachariae, Silke, Loeffler, Markus, Mecklin, Jukka-Pekka, Kloor, Matthias, and Vasen, Hans F.

Abstract

BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are

Published
2020

26. Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study

Author

Bucksch, Karolin, Zachariae, Silke, Aretz, Stefan, Buettner, Reinhard, Holinski-Feder, Elke, Holzapfel, Stefanie, Hueneburg, Robert, Kloor, Matthias, Doeberitz, Magnus von Knebel, Morak, Monika, Moeslein, Gabriela, Nattermann, Jacob, Perne, Claudia, Rahner, Nils, Schmiegel, Wolff, Schulmann, Karsten, Steinke-Lange, Verena, Strassburg, Christian P., Vangala, Deepak B., Weitz, Juergen, Loeffler, Markus, Engel, Christoph, Bucksch, Karolin, Zachariae, Silke, Aretz, Stefan, Buettner, Reinhard, Holinski-Feder, Elke, Holzapfel, Stefanie, Hueneburg, Robert, Kloor, Matthias, Doeberitz, Magnus von Knebel, Morak, Monika, Moeslein, Gabriela, Nattermann, Jacob, Perne, Claudia, Rahner, Nils, Schmiegel, Wolff, Schulmann, Karsten, Steinke-Lange, Verena, Strassburg, Christian P., Vangala, Deepak B., Weitz, Juergen, Loeffler, Markus, and Engel, Christoph

Abstract

BackgroundIndividuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population.MethodsData was taken from the registry of the German Consortium for Familial Intestinal Cancer, where individuals were followed up prospectively within the framework of an intensified surveillance programme at recommended annual examination intervals. A total of 1120 LS, 594 LLS, and 116 FCCX individuals were analysed. From this total sample, eight different cohorts were defined, in which age-dependent cumulative risks and standardised incidence ratios were calculated regarding the first incident occurrence of any, colorectal, stomach, small bowel, urothelial, female breast, ovarian, and endometrial cancer, separately for LS, LLS, and FCCX.ResultsThe number of individuals at risk for first incident cancer ranged from 322 to 1102 in LS, 120 to 586 in LLS, and 40 to 116 in FCCX, depending on the cancer type of interest. For most cancer types, higher risks were observed in LS compared to LLS, FCCX, and the general population. Risks for any, colorectal, stomach, urothelial, and endometrial cancer were significantly higher in LLS compared to the general population. No significantly increased risks could be detected in FCCX compared to LLS patients, and the general population. Colorectal and endometrial cancer risks tended to be higher in LLS

Published
2020

27. Evaluating the performance of the breast cancer genetic risk models BOADICEA, IBIS, BRCAPRO and Claus for predicting BRCA1/2 mutation carrier probabilities: a study based on 7352 families from the German Hereditary Breast and Ovarian Cancer Consortium

Author

Fischer, Christine, Kuchenbäcker, Karoline, Engel, Christoph, Zachariae, Silke, Rhiem, Kerstin, Meindl, Alfons, Rahner, Nils, Dikow, Nicola, Plendl, Hansjörg, Debatin, Irmgard, Grimm, Tiemo, Gadzicki, Dorothea, Flöttmann, Ricarda, Horvath, Judit, Schröck, Evelin, Stock, Friedrich, Schäfer, Dieter, Schwaab, Ira, Kartsonaki, Christiana, Mavaddat, Nasim, Schlegelberger, Brigitte, Antoniou, Antonis C, and Schmutzler, Rita

Published
2013
Full Text
View/download PDF

28. Depressive Symptomatology in Early Retirees Associated With Reason for Retirement—Results From the Population-Based LIFE-Adult-Study

Author

Zuelke, Andrea E., primary, Roehr, Susanne, additional, Schroeter, Matthias L., additional, Witte, A. Veronica, additional, Hinz, Andreas, additional, Glaesmer, Heide, additional, Engel, Christoph, additional, Enzenbach, Cornelia, additional, Zachariae, Silke, additional, Zeynalova, Samira, additional, Loeffler, Markus, additional, Villringer, Arno, additional, and Riedel-Heller, Steffi G., additional

Published
2020
Full Text
View/download PDF

29. Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome

Author

Engel, Christoph, primary, Ahadova, Aysel, additional, Seppälä, Toni T., additional, Aretz, Stefan, additional, Bigirwamungu-Bargeman, Marloes, additional, Bläker, Hendrik, additional, Bucksch, Karolin, additional, Büttner, Reinhard, additional, de Vos tot Nederveen Cappel, Wouter T., additional, Endris, Volker, additional, Holinski-Feder, Elke, additional, Holzapfel, Stefanie, additional, Hüneburg, Robert, additional, Jacobs, Maarten A.J.M., additional, Koornstra, Jan J., additional, Langers, Alexandra M., additional, Lepistö, Anna, additional, Morak, Monika, additional, Möslein, Gabriela, additional, Peltomäki, Päivi, additional, Pylvänäinen, Kirsi, additional, Rahner, Nils, additional, Renkonen-Sinisalo, Laura, additional, Schulmann, Karsten, additional, Steinke-Lange, Verena, additional, Stenzinger, Albrecht, additional, Strassburg, Christian P., additional, van de Meeberg, Paul C., additional, van Kouwen, Mariette, additional, van Leerdam, Monique, additional, Vangala, Deepak B., additional, Vecht, Juda, additional, Verhulst, Marie-Louise, additional, von Knebel Doeberitz, Magnus, additional, Weitz, Jürgen, additional, Zachariae, Silke, additional, Loeffler, Markus, additional, Mecklin, Jukka-Pekka, additional, Kloor, Matthias, additional, and Vasen, Hans F., additional

Published
2020
Full Text
View/download PDF

30. High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer

Author

Bick, Ulrich, Engel, Christoph, Krug, Barbara, Heindel, Walter, Fallenberg, Eva M., Rhiem, Kerstin, Maintz, David, Golatta, Michael, Speiser, Dorothee, Rjosk-Dendorfer, Dorothea, Laemmer-Skarke, Irina, Dietzel, Frederic, Schaefer, Karl Werner Fritz, Leinert, Elena, Weigel, Stefanie, Sauer, Stephanie, Pertschy, Stefanie, Hofmockel, Thomas, Hagert-Winkler, Anne, Kast, Karin, Quante, Anne, Meindl, Alfons, Kiechle, Marion, Loeffler, Markus, Schmutzler, Rita K., Blohmer, Jens-Uwe, Horn, Denise, Varon-Mateeva, Raymonda, Huebbel, Verena, Herold, Natalie, Puesken, Michael, Wimberger, Pauline, Meisel, Cornelia, Keller, Katja, Antoch, Gerald, Vesper, Anne-Sophie, Fehm, Tanja N., Schlegelberger, Brigitte, Auber, Bernd, Wallaschek, Hannah, Heil, Joerg, Schott, Sarah, Dikow, Nicola, Mundhenke, Christoph, Arnold, Norbert, Caliebe, Almuth, Briest, Susanne, Lemke, Johannes, Gril, Sabine, Pfeifer, Katharina, Ramser, Juliane, Mahner, Sven, Ditsch, Nina, Zeder-Goess, Christine, Tio, Joke, Burg, Matthias, Horvath, Judith, Siebert, Reiner, Bartholomae, Jasmin, Janni, Wolfgang, Bley, Thorsten, Woeckel, Achim, Haaf, Thomas, Zachariae, Silke, Bucksch, Karolin, Enders, Ute, Bick, Ulrich, Engel, Christoph, Krug, Barbara, Heindel, Walter, Fallenberg, Eva M., Rhiem, Kerstin, Maintz, David, Golatta, Michael, Speiser, Dorothee, Rjosk-Dendorfer, Dorothea, Laemmer-Skarke, Irina, Dietzel, Frederic, Schaefer, Karl Werner Fritz, Leinert, Elena, Weigel, Stefanie, Sauer, Stephanie, Pertschy, Stefanie, Hofmockel, Thomas, Hagert-Winkler, Anne, Kast, Karin, Quante, Anne, Meindl, Alfons, Kiechle, Marion, Loeffler, Markus, Schmutzler, Rita K., Blohmer, Jens-Uwe, Horn, Denise, Varon-Mateeva, Raymonda, Huebbel, Verena, Herold, Natalie, Puesken, Michael, Wimberger, Pauline, Meisel, Cornelia, Keller, Katja, Antoch, Gerald, Vesper, Anne-Sophie, Fehm, Tanja N., Schlegelberger, Brigitte, Auber, Bernd, Wallaschek, Hannah, Heil, Joerg, Schott, Sarah, Dikow, Nicola, Mundhenke, Christoph, Arnold, Norbert, Caliebe, Almuth, Briest, Susanne, Lemke, Johannes, Gril, Sabine, Pfeifer, Katharina, Ramser, Juliane, Mahner, Sven, Ditsch, Nina, Zeder-Goess, Christine, Tio, Joke, Burg, Matthias, Horvath, Judith, Siebert, Reiner, Bartholomae, Jasmin, Janni, Wolfgang, Bley, Thorsten, Woeckel, Achim, Haaf, Thomas, Zachariae, Silke, Bucksch, Karolin, and Enders, Ute

Abstract

Purpose To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Methods A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. Results A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5 (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9 parts per thousand (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. Conclusions High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Published
2019

31. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., Spurdle, Amanda B., Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., and Spurdle, Amanda B.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

32. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., primary, Tudini, Emma, additional, Li, Hongyan, additional, Hahnen, Eric, additional, Wappenschmidt, Barbara, additional, Feliubadaló, Lidia, additional, Aalfs, Cora M., additional, Agata, Simona, additional, Aittomäki, Kristiina, additional, Alducci, Elisa, additional, Alonso‐Cerezo, María Concepción, additional, Arnold, Norbert, additional, Auber, Bernd, additional, Austin, Rachel, additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barbieri, Elena, additional, Bartram, Claus R., additional, Blanco, Ana, additional, Blümcke, Britta, additional, Bonache, Sandra, additional, Bonanni, Bernardo, additional, Borg, Åke, additional, Bortesi, Beatrice, additional, Brunet, Joan, additional, Bruzzone, Carla, additional, Bucksch, Karolin, additional, Cagnoli, Giulia, additional, Caldés, Trinidad, additional, Caliebe, Almuth, additional, Caligo, Maria A., additional, Calvello, Mariarosaria, additional, Capone, Gabriele L., additional, Caputo, Sandrine M., additional, Carnevali, Ileana, additional, Carrasco, Estela, additional, Caux‐Moncoutier, Virginie, additional, Cavalli, Pietro, additional, Cini, Giulia, additional, Clarke, Edward M., additional, Concolino, Paola, additional, Cops, Elisa J., additional, Cortesi, Laura, additional, Couch, Fergus J., additional, Darder, Esther, additional, Hoya, Miguel, additional, Dean, Michael, additional, Debatin, Irmgard, additional, Del Valle, Jesús, additional, Delnatte, Capucine, additional, Derive, Nicolas, additional, Diez, Orland, additional, Ditsch, Nina, additional, Domchek, Susan M., additional, Dutrannoy, Véronique, additional, Eccles, Diana M., additional, Ehrencrona, Hans, additional, Enders, Ute, additional, Evans, D. Gareth, additional, Farra, Chantal, additional, Faust, Ulrike, additional, Felbor, Ute, additional, Feroce, Irene, additional, Fine, Miriam, additional, Foulkes, William D., additional, Galvao, Henrique C.R., additional, Gambino, Gaetana, additional, Gehrig, Andrea, additional, Gensini, Francesca, additional, Gerdes, Anne‐Marie, additional, Germani, Aldo, additional, Giesecke, Jutta, additional, Gismondi, Viviana, additional, Gómez, Carolina, additional, Garcia, Encarna B., additional, González, Sara, additional, Grau, Elia, additional, Grill, Sabine, additional, Gross, Eva, additional, Guerrieri‐Gonzaga, Aliana, additional, Guillaud‐Bataille, Marine, additional, Gutiérrez‐Enríquez, Sara, additional, Haaf, Thomas, additional, Hackmann, Karl, additional, Hansen, Thomas V.O., additional, Harris, Marion, additional, Hauke, Jan, additional, Heinrich, Tilman, additional, Hellebrand, Heide, additional, Herold, Karen N., additional, Honisch, Ellen, additional, Horvath, Judit, additional, Houdayer, Claude, additional, Hübbel, Verena, additional, Iglesias, Silvia, additional, Izquierdo, Angel, additional, James, Paul A., additional, Janssen, Linda A.M., additional, Jeschke, Udo, additional, Kaulfuß, Silke, additional, Keupp, Katharina, additional, Kiechle, Marion, additional, Kölbl, Alexandra, additional, Krieger, Sophie, additional, Kruse, Torben A., additional, Kvist, Anders, additional, Lalloo, Fiona, additional, Larsen, Mirjam, additional, Lattimore, Vanessa L., additional, Lautrup, Charlotte, additional, Ledig, Susanne, additional, Leinert, Elena, additional, Lewis, Alexandra L., additional, Lim, Joanna, additional, Loeffler, Markus, additional, López‐Fernández, Adrià, additional, Lucci‐Cordisco, Emanuela, additional, Maass, Nicolai, additional, Manoukian, Siranoush, additional, Marabelli, Monica, additional, Matricardi, Laura, additional, Meindl, Alfons, additional, Michelli, Rodrigo D., additional, Moghadasi, Setareh, additional, Moles‐Fernández, Alejandro, additional, Montagna, Marco, additional, Montalban, Gemma, additional, Monteiro, Alvaro N., additional, Montes, Eva, additional, Mori, Luigi, additional, Moserle, Lidia, additional, Müller, Clemens R., additional, Mundhenke, Christoph, additional, Naldi, Nadia, additional, Nathanson, Katherine L., additional, Navarro, Matilde, additional, Nevanlinna, Heli, additional, Nichols, Cassandra B., additional, Niederacher, Dieter, additional, Nielsen, Henriette R., additional, Ong, Kai‐ren, additional, Pachter, Nicholas, additional, Palmero, Edenir I., additional, Papi, Laura, additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Perez‐Segura, Pedro, additional, Pfeifer, Katharina, additional, Pineda, Marta, additional, Pohl‐Rescigno, Esther, additional, Poplawski, Nicola K., additional, Porfirio, Berardino, additional, Quante, Anne S., additional, Ramser, Juliane, additional, Reis, Rui M., additional, Revillion, Françoise, additional, Rhiem, Kerstin, additional, Riboli, Barbara, additional, Ritter, Julia, additional, Rivera, Daniela, additional, Rofes, Paula, additional, Rump, Andreas, additional, Salinas, Monica, additional, Sánchez de Abajo, Ana María, additional, Schmidt, Gunnar, additional, Schoenwiese, Ulrike, additional, Seggewiß, Jochen, additional, Solanes, Ares, additional, Steinemann, Doris, additional, Stiller, Mathias, additional, Stoppa‐Lyonnet, Dominique, additional, Sullivan, Kelly J., additional, Susman, Rachel, additional, Sutter, Christian, additional, Tavtigian, Sean V., additional, Teo, Soo H., additional, Teulé, Alex, additional, Thomassen, Mads, additional, Tibiletti, Maria Grazia, additional, Tischkowitz, Marc, additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Tornero, Eva, additional, Törngren, Therese, additional, Torres‐Esquius, Sara, additional, Toss, Angela, additional, Trainer, Alison H., additional, Tucker, Katherine M., additional, Asperen, Christi J., additional, Mackelenbergh, Marion T., additional, Varesco, Liliana, additional, Vargas‐Parra, Gardenia, additional, Varon, Raymonda, additional, Vega, Ana, additional, Velasco, Ángela, additional, Vesper, Anne‐Sophie, additional, Viel, Alessandra, additional, Vreeswijk, Maaike P. G., additional, Wagner, Sebastian A., additional, Waha, Anke, additional, Walker, Logan C., additional, Walters, Rhiannon J., additional, Wang‐Gohrke, Shan, additional, Weber, Bernhard H. F., additional, Weichert, Wilko, additional, Wieland, Kerstin, additional, Wiesmüller, Lisa, additional, Witzel, Isabell, additional, Wöckel, Achim, additional, Woodward, Emma R., additional, Zachariae, Silke, additional, Zampiga, Valentina, additional, Zeder‐Göß, Christine, additional, Investigators, KConFab, additional, Lázaro, Conxi, additional, Nicolo, Arcangela, additional, Radice, Paolo, additional, Engel, Christoph, additional, Schmutzler, Rita K., additional, Goldgar, David E., additional, and Spurdle, Amanda B., additional

Published
2019
Full Text
View/download PDF

33. Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history

Author

German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), Engel, Christoph, Rhiem, Kerstin E. M., Hahnen, Eric Thomas, Loibl, Sibylle, Weber, Karsten E., Seiler, Sabine, Zachariae, Silke, Hauke, Jan, Wappenschmidt, Barbara, Waha, Anke, Blümcke, Britta, Kiechle, Marion, Meindl, Alfons, Niederacher, Dieter, Bartram, Claus R., Speiser, Dorothee, Schlegelberger, Brigitte, Arnold, Norbert, Wieacker, Peter, Leinert, Elena, Gehrig, Andrea, Briest, Susanne, Kast, Karin, Rieß, Olaf, Emons, Günter, Weber, Bernhard H. F., Engel, Jutta, Schmutzler, Rita Katharina, German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), Engel, Christoph, Rhiem, Kerstin E. M., Hahnen, Eric Thomas, Loibl, Sibylle, Weber, Karsten E., Seiler, Sabine, Zachariae, Silke, Hauke, Jan, Wappenschmidt, Barbara, Waha, Anke, Blümcke, Britta, Kiechle, Marion, Meindl, Alfons, Niederacher, Dieter, Bartram, Claus R., Speiser, Dorothee, Schlegelberger, Brigitte, Arnold, Norbert, Wieacker, Peter, Leinert, Elena, Gehrig, Andrea, Briest, Susanne, Kast, Karin, Rieß, Olaf, Emons, Günter, Weber, Bernhard H. F., Engel, Jutta, and Schmutzler, Rita Katharina

Abstract

Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years. Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.

Published
2018

34. Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.

Author

Engel, Christoph, Fischer, Christine, Zachariae, Silke, Bucksch, Karolin, Rhiem, Kerstin, Giesecke, Jutta, Herold, Natalie, Wappenschmidt, Barbara, Hübbel, Verena, Maringa, Monika, Reichstein‐Gnielinski, Simone, Hahnen, Eric, Bartram, Claus R., Dikow, Nicola, Schott, Sarah, Speiser, Dorothee, Horn, Denise, Fallenberg, Eva M., Kiechle, Marion, and Quante, Anne S.

Subjects
BREAST cancer, BREAST imaging, OVARIAN cancer, HORMONE receptor positive breast cancer, FILAGGRIN
Abstract

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age‐dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person‐years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8–70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1–56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9–20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9–29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2–19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8–6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6–31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4–12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2–5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk. What's new? Women with a family history of breast cancer often have relatives who test negative for pathogenic BRCA1/2 mutations. Compared to BRCA1/2‐positive women, however, little is known about breast cancer risk among women from BRCA1/2‐negative families. In this study of women with and without BRCA1/2 mutations who participated in a German breast imaging surveillance program between 2005 and 2017, risk of first breast cancer was markedly lower in BRCA1/2‐negative women compared to BRCA1/2 mutation carriers. Relative to the general population, unilateral breast cancer risk was elevated in BRCA1/2‐negative women, while contralateral breast cancer risk was similar between the two groups. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

35. The LIFE-Adult-Study: Objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany

Author

Loeffler, Markus, Engel, Christoph, Ahnert, Peter, Alfermann, Dorothee, Arelin, Katrin, Baber, Ronny, Beutner, Frank, Binder, Hans, Brähler, Elmar, Burkhardt, Ralph, Ceglarek, Uta, Enzenbach, Cornelia, Fuchs, Michael, Glaesmer, Heide, Girlich, Friederike, Hagendorff, Andreas, Häntzsch, Madlen, Hegerl, Ulrich, Henger, Sylvia, Hensch, Tilman, Hinz, Andreas, Holzendorf, Volker, Husser, Daniela, Kersting, Anette, Kiel, Alexander, Kirsten, Toralf, Kratzsch, Jürgen, Krohn, Knut, Luck, Tobias, Melzer, Susanne, Netto, Jeffrey, Nüchter, Matthias, Raschpichler, Matthias, Rauscher, Franziska G., Riedel-Heller, Steffi G., Sander, Christian, Scholz, Markus, Schönknecht, Peter, Schroeter, Matthias L., Simon, Jan-Christoph, Speer, Ronald, Stäker, Julia, Stein, Robert, Stöbel-Richter, Yve, Stumvoll, Michael, Tarnok, Attila, Teren, Andrej, Teupser, Daniel, Then, Francisca S., Tönjes, Anke, Treudler, Regina, Villringer, Arno, Weissgerber, Alexander, Wiedemann, Peter, Zachariae, Silke, Wirkner, Kerstin, and Thiery, Joachim

Subjects
Adult, Male, Population based, Urban Population, Epidemiology, Diseases of civilization, Health Status, Public Health, Environmental and Occupational Health, Middle Aged, Health Surveys, Cohort Studies, Study Protocol, Research Design, Germany, Population Surveillance, Health Status Indicators, Humans, Female, Cohort study, Physical Examination, Aged
Abstract

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Published
2015

36. Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer

Author

Kast, Karin, Rhiem, Kerstin, Wappenschmidt, Barbara, Hahnen, Eric, Hauke, Jan, Bluemcke, Britta, Zarghooni, Verena, Herold, Natalie, Ditsch, Nina, Kiechle, Marion, Braun, Michael, Fischer, Christine, Dikow, Nicola, Schott, Sarah, Rahner, Nils, Niederacher, Dieter, Fehm, Tanja, Gehrig, Andrea, Mueller-Reible, Clemens, Arnold, Norbert, Maass, Nicolai, Borck, Guntram, de Gregorio, Nikolaus, Scholz, Caroline, Auber, Bernd, Varon-Manteeva, Raymonda, Speiser, Dorothee, Horvath, Judit, Lichey, Nadine, Wimberger, Pauline, Stark, Sylvia, Faust, Ulrike, Weber, Bernhard H. F., Emons, Gunter, Zachariae, Silke, Meindl, Alfons, Schmutzler, Rita K., Engel, Christoph, Kast, Karin, Rhiem, Kerstin, Wappenschmidt, Barbara, Hahnen, Eric, Hauke, Jan, Bluemcke, Britta, Zarghooni, Verena, Herold, Natalie, Ditsch, Nina, Kiechle, Marion, Braun, Michael, Fischer, Christine, Dikow, Nicola, Schott, Sarah, Rahner, Nils, Niederacher, Dieter, Fehm, Tanja, Gehrig, Andrea, Mueller-Reible, Clemens, Arnold, Norbert, Maass, Nicolai, Borck, Guntram, de Gregorio, Nikolaus, Scholz, Caroline, Auber, Bernd, Varon-Manteeva, Raymonda, Speiser, Dorothee, Horvath, Judit, Lichey, Nadine, Wimberger, Pauline, Stark, Sylvia, Faust, Ulrike, Weber, Bernhard H. F., Emons, Gunter, Zachariae, Silke, Meindl, Alfons, Schmutzler, Rita K., and Engel, Christoph

Abstract

Purpose To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history. Patients and methods Data from 21 401 families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient. Results The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%). Conclusions Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

Published
2016

37. Prevalence ofBRCA1/2germline mutations in 21 401 families with breast and ovarian cancer

Author

Kast, Karin, primary, Rhiem, Kerstin, additional, Wappenschmidt, Barbara, additional, Hahnen, Eric, additional, Hauke, Jan, additional, Bluemcke, Britta, additional, Zarghooni, Verena, additional, Herold, Natalie, additional, Ditsch, Nina, additional, Kiechle, Marion, additional, Braun, Michael, additional, Fischer, Christine, additional, Dikow, Nicola, additional, Schott, Sarah, additional, Rahner, Nils, additional, Niederacher, Dieter, additional, Fehm, Tanja, additional, Gehrig, Andrea, additional, Mueller-Reible, Clemens, additional, Arnold, Norbert, additional, Maass, Nicolai, additional, Borck, Guntram, additional, de Gregorio, Nikolaus, additional, Scholz, Caroline, additional, Auber, Bernd, additional, Varon-Manteeva, Raymonda, additional, Speiser, Dorothee, additional, Horvath, Judit, additional, Lichey, Nadine, additional, Wimberger, Pauline, additional, Stark, Sylvia, additional, Faust, Ulrike, additional, Weber, Bernhard H F, additional, Emons, Gunter, additional, Zachariae, Silke, additional, Meindl, Alfons, additional, Schmutzler, Rita K, additional, and Engel, Christoph, additional

Published
2016
Full Text
View/download PDF

39. The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany

Author

Loeffler, Markus, primary, Engel, Christoph, additional, Ahnert, Peter, additional, Alfermann, Dorothee, additional, Arelin, Katrin, additional, Baber, Ronny, additional, Beutner, Frank, additional, Binder, Hans, additional, Brähler, Elmar, additional, Burkhardt, Ralph, additional, Ceglarek, Uta, additional, Enzenbach, Cornelia, additional, Fuchs, Michael, additional, Glaesmer, Heide, additional, Girlich, Friederike, additional, Hagendorff, Andreas, additional, Häntzsch, Madlen, additional, Hegerl, Ulrich, additional, Henger, Sylvia, additional, Hensch, Tilman, additional, Hinz, Andreas, additional, Holzendorf, Volker, additional, Husser, Daniela, additional, Kersting, Anette, additional, Kiel, Alexander, additional, Kirsten, Toralf, additional, Kratzsch, Jürgen, additional, Krohn, Knut, additional, Luck, Tobias, additional, Melzer, Susanne, additional, Netto, Jeffrey, additional, Nüchter, Matthias, additional, Raschpichler, Matthias, additional, Rauscher, Franziska G., additional, Riedel-Heller, Steffi G., additional, Sander, Christian, additional, Scholz, Markus, additional, Schönknecht, Peter, additional, Schroeter, Matthias L., additional, Simon, Jan-Christoph, additional, Speer, Ronald, additional, Stäker, Julia, additional, Stein, Robert, additional, Stöbel-Richter, Yve, additional, Stumvoll, Michael, additional, Tarnok, Attila, additional, Teren, Andrej, additional, Teupser, Daniel, additional, Then, Francisca S., additional, Tönjes, Anke, additional, Treudler, Regina, additional, Villringer, Arno, additional, Weissgerber, Alexander, additional, Wiedemann, Peter, additional, Zachariae, Silke, additional, Wirkner, Kerstin, additional, and Thiery, Joachim, additional

Published
2015
Full Text
View/download PDF

43. The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study

Author

Rhiem, Kerstin, primary, Engel, Christoph, additional, Graeser, Monika, additional, Zachariae, Silke, additional, Kast, Karin, additional, Kiechle, Marion, additional, Ditsch, Nina, additional, Janni, Wolfgang, additional, Mundhenke, Christoph, additional, Golatta, Michael, additional, Varga, Dominic, additional, Preisler-Adams, Sabine, additional, Heinrich, Tilman, additional, Bick, Ulrich, additional, Gadzicki, Dorothea, additional, Briest, Susanne, additional, Meindl, Alfons, additional, and Schmutzler, Rita K, additional

Published
2012
Full Text
View/download PDF

44. Adenoma and colorectal cancer risks in Lynch syndrome, Lynch-like syndrome and familial colorectal cancer type X.

Author

Bucksch K, Zachariae S, Ahadova A, Aretz S, Büttner R, Görgens H, Holinski-Feder E, Hüneburg R, Kloor M, von Knebel Doeberitz M, Ladigan-Badura S, Moeslein G, Morak M, Nattermann J, Nguyen HP, Perne C, Redler S, Schmetz A, Steinke-Lange V, Surowy H, Vangala DB, Weitz J, Loeffler M, and Engel C

Subjects
Adenoma etiology, Adenoma metabolism, Adult, Aged, Colorectal Neoplasms etiology, Colorectal Neoplasms metabolism, Female, Follow-Up Studies, Humans, Male, Middle Aged, MutL Protein Homolog 1 genetics, MutS Homolog 2 Protein genetics, Mutation, Prognosis, Prospective Studies, Risk Factors, Adenoma pathology, Biomarkers, Tumor genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms, Hereditary Nonpolyposis classification, Colorectal Neoplasms, Hereditary Nonpolyposis complications
Abstract

Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk-adapted surveillance policies in LS, LLS and FCCX., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2022
Full Text
View/download PDF

45. [HerediCaRe: Documentation and IT Solution of a Specialized Registry for Hereditary Breast and Ovarian Cancer].

Author

Engel C, Wieland K, Zachariae S, Bucksch K, Enders U, Schoenwiese U, Yahiaoui-Doktor M, Keupp K, Waha A, Hahnen E, Remy R, Ernst C, Loeffler M, and Schmutzler RK

Subjects
Female, Germany, Humans, Registries, Software, Documentation, Ovarian Neoplasms genetics
Abstract

The national registry "HerediCaRe" for the evaluation and improvement of risk-adjusted prevention in hereditary breast and ovarian cancer is one of six "model registries in health services research" funded by the BMBF. In this paper, we describe and discuss the documentation and IT solution chosen for standardized data collection based on the specific functional requirements previously defined. The documentation is divided into different modules to be used individually for each patient, which are based on a previously defined catalog of documentation items. Due to special functional requirements, a specific data entry application based on ORACLE and ORACLE Forms was developed and implemented. The specific requirements included the integration of graphical pedigree representations, the structured upload of pedigree data and molecular genetic information, the automated transfer of old data from the previous system, as well as the free programmability of complex database queries for central data quality control. A database for patient-independent management of genetic risk variants was seamlessly integrated into the application and linked to the patient-related data. The advantages and disadvantages of the chosen IT solution are critically discussed. Overall, we come to the conclusion that, in view of the complex documentation and the special functional requirements, there are no alternative ready-made software products to the in-house development we have chosen., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Published
2021
Full Text
View/download PDF

46. Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study.

Author

Bucksch K, Zachariae S, Aretz S, Büttner R, Holinski-Feder E, Holzapfel S, Hüneburg R, Kloor M, von Knebel Doeberitz M, Morak M, Möslein G, Nattermann J, Perne C, Rahner N, Schmiegel W, Schulmann K, Steinke-Lange V, Strassburg CP, Vangala DB, Weitz J, Loeffler M, and Engel C

Subjects
Adult, Aged, Aged, 80 and over, Brain Neoplasms genetics, Colorectal Neoplasms genetics, DNA Mismatch Repair, Female, Follow-Up Studies, Humans, Male, Microsatellite Instability, Middle Aged, Neoplastic Syndromes, Hereditary genetics, Prognosis, Prospective Studies, Survival Rate, Biomarkers, Tumor genetics, Brain Neoplasms epidemiology, Colorectal Neoplasms classification, Colorectal Neoplasms epidemiology, DNA Repair Enzymes genetics, Genetic Predisposition to Disease, Genetics, Population, Neoplastic Syndromes, Hereditary epidemiology
Abstract

Background: Individuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population., Methods: Data was taken from the registry of the German Consortium for Familial Intestinal Cancer, where individuals were followed up prospectively within the framework of an intensified surveillance programme at recommended annual examination intervals. A total of 1120 LS, 594 LLS, and 116 FCCX individuals were analysed. From this total sample, eight different cohorts were defined, in which age-dependent cumulative risks and standardised incidence ratios were calculated regarding the first incident occurrence of any, colorectal, stomach, small bowel, urothelial, female breast, ovarian, and endometrial cancer, separately for LS, LLS, and FCCX., Results: The number of individuals at risk for first incident cancer ranged from 322 to 1102 in LS, 120 to 586 in LLS, and 40 to 116 in FCCX, depending on the cancer type of interest. For most cancer types, higher risks were observed in LS compared to LLS, FCCX, and the general population. Risks for any, colorectal, stomach, urothelial, and endometrial cancer were significantly higher in LLS compared to the general population. No significantly increased risks could be detected in FCCX compared to LLS patients, and the general population. Colorectal and endometrial cancer risks tended to be higher in LLS than in FCCX., Conclusions: The characterisation of cancer risks in patients with LLS and FCCX is important to develop appropriate surveillance programmes for these specific intermediate risk groups. Larger prospective studies are needed to obtain more precise risk estimates.

Published
2020
Full Text
View/download PDF

47. Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer.

Author

Kast K, Rhiem K, Wappenschmidt B, Hahnen E, Hauke J, Bluemcke B, Zarghooni V, Herold N, Ditsch N, Kiechle M, Braun M, Fischer C, Dikow N, Schott S, Rahner N, Niederacher D, Fehm T, Gehrig A, Mueller-Reible C, Arnold N, Maass N, Borck G, de Gregorio N, Scholz C, Auber B, Varon-Manteeva R, Speiser D, Horvath J, Lichey N, Wimberger P, Stark S, Faust U, Weber BH, Emons G, Zachariae S, Meindl A, Schmutzler RK, and Engel C

Subjects
Adult, Female, Genetic Predisposition to Disease genetics, Genetic Testing methods, Humans, Male, Middle Aged, Prevalence, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms genetics, Breast Neoplasms, Male genetics, Germ-Line Mutation genetics, Ovarian Neoplasms genetics
Abstract

Purpose: To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history., Patients and Methods: Data from 21 401 families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient., Results: The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%)., Conclusions: Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results