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5 results on '"Nadine Lichey"'

1. Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer

Author

Nana Weber-Lassalle, Julika Borde, Konstantin Weber-Lassalle, Judit Horváth, Dieter Niederacher, Norbert Arnold, Silke Kaulfuß, Corinna Ernst, Victoria G. Paul, Ellen Honisch, Kristina Klaschik, Alexander E. Volk, Christian Kubisch, Steffen Rapp, Nadine Lichey, Janine Altmüller, Louisa Lepkes, Esther Pohl-Rescigno, Holger Thiele, Peter Nürnberg, Mirjam Larsen, Lisa Richters, Kerstin Rhiem, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Rita K. Schmutzler, Eric Hahnen, and Jan Hauke

Subjects
Early onset breast cancer, Ovarian cancer, BARD1, Germline mutations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The role of the BARD1 gene in breast cancer (BC) and ovarian cancer (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess the role of deleterious BARD1 germline variants in BC/OC predisposition in a sample of 4920 BRCA1/2-negative female BC/OC index patients of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Methods A total of 4469 female index patients with BC, 451 index patients with OC, and 2767 geographically matched female control individuals were screened for loss-of-function (LoF) mutations and potentially damaging rare missense variants in BARD1. All patients met the inclusion criteria of the GC-HBOC for germline testing and reported at least one relative with BC or OC. Additional control datasets (Exome Aggregation Consortium, ExAC; Fabulous Ladies Over Seventy, FLOSSIES) were included for the calculation of odds ratios (ORs). Results We identified LoF variants in 23 of 4469 BC index patients (0.51%) and in 36 of 37,265 control individuals (0.10%), resulting in an OR of 5.35 (95% confidence interval [CI] = 3.17–9.04; P

Published
2019
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2. Gene panel testing of 5589 BRCA1/2‐negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Jan Hauke, Judit Horvath, Eva Groß, Andrea Gehrig, Ellen Honisch, Karl Hackmann, Gunnar Schmidt, Norbert Arnold, Ulrike Faust, Christian Sutter, Julia Hentschel, Shan Wang‐Gohrke, Mateja Smogavec, Bernhard H. F. Weber, Nana Weber‐Lassalle, Konstantin Weber‐Lassalle, Julika Borde, Corinna Ernst, Janine Altmüller, Alexander E. Volk, Holger Thiele, Verena Hübbel, Peter Nürnberg, Katharina Keupp, Beatrix Versmold, Esther Pohl, Christian Kubisch, Sabine Grill, Victoria Paul, Natalie Herold, Nadine Lichey, Kerstin Rhiem, Nina Ditsch, Christian Ruckert, Barbara Wappenschmidt, Bernd Auber, Andreas Rump, Dieter Niederacher, Thomas Haaf, Juliane Ramser, Bernd Dworniczak, Christoph Engel, Alfons Meindl, Rita K. Schmutzler, and Eric Hahnen

Subjects
Breast cancer predisposition, hereditary breast cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The prevalence of germ line mutations in non‐BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK2 gene (2.5%), followed by ATM (1.5%) and PALB2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM (OR: 3.63, 95%CI: 2.67–4.94), CDH1 (OR: 17.04, 95%CI: 3.54–82), CHEK2 (OR: 2.93, 95%CI: 2.29–3.75), PALB2 (OR: 9.53, 95%CI: 6.25–14.51), and TP53 (OR: 7.30, 95%CI: 1.22–43.68). NBN germ line mutations were not significantly associated with BC risk (OR:1.39, 95%CI: 0.73–2.64). Due to their low mutation prevalence, the RAD51C and RAD51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK2 and TP53 in BC index patients. Compared with the overall sample, only TP53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK2, PALB2, and TP53 genes with bilateral BC. Both, ATM and CHEK2, were negatively associated with triple‐negative breast cancer (TNBC) and estrogen receptor (ER)‐negative tumor phenotypes. A particularly high CHEK2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 (HER2)‐positive tumors.

Published
2018
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3. Prevalence ofBRCA1/2germline mutations in 21 401 families with breast and ovarian cancer

Author

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

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Breast Neoplasms, Pedigree chart, Breast Neoplasms, Male, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Germline mutation, Prevalence, Genetics, medicine, Humans, Genetic Predisposition to Disease, Mutation detection, Genetic Testing, Germ-Line Mutation, Genetics (clinical), Genetic testing, BRCA2 Protein, Ovarian Neoplasms, Gynecology, medicine.diagnostic_test, BRCA1 Protein, business.industry, Cancer, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Female, Ovarian cancer, business
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 (

Published
2016
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4. Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Dieter Niederacher, Mateja Smogavec, Konstantin Weber-Lassalle, Ellen Honisch, Judit Horvath, Victoria G. Paul, Christian Ruckert, Thomas Haaf, Norbert Arnold, N Herold, Katharina Keupp, Bernhard H. F. Weber, Julika Borde, Beatrix Versmold, Janine Altmüller, Alfons Meindl, Andreas Rump, Sabine Grill, Verena Hübbel, Christoph Engel, Shan Wang-Gohrke, Juliane Ramser, Holger Thiele, Christian Kubisch, Bernd Dworniczak, Alexander E Volk, Nana Weber-Lassalle, Jan Hauke, Kerstin Rhiem, Corinna Ernst, Gunnar Schmidt, Nadine Lichey, Peter Nürnberg, Christian Sutter, Barbara Wappenschmidt, Julia Hentschel, Nina Ditsch, Rita K. Schmutzler, Andrea Gehrig, Bernd Auber, Karl Hackmann, Eva Groß, Esther Pohl, Eric Hahnen, and Ulrike Faust

Subjects
0301 basic medicine, Oncology, Cancer Research, Genes, BRCA2, Genes, BRCA1, Estrogen receptor, 0302 clinical medicine, Odds Ratio, Prevalence, Missense mutation, 10. No inequality, skin and connective tissue diseases, Exome, Original Research, Cancer Biology, Aged, 80 and over, medicine.diagnostic_test, hereditary breast cancer, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Hereditary Breast and Ovarian Cancer Syndrome, Female, Adult, medicine.medical_specialty, PALB2, 03 medical and health sciences, Young Adult, Breast cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, Genetic Predisposition to Disease, Genetic Testing, ddc:610, CHEK2, Genetic Association Studies, Genetic testing, Aged, business.industry, Genetic Variation, medicine.disease, 030104 developmental biology, Breast cancer predisposition, Case-Control Studies, business, Ovarian cancer
Abstract

The prevalence of germ line mutations in non-BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK2 gene (2.5%), followed by ATM (1.5%) and PALB2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM (OR: 3.63, 95% CI: 2.67-4.94), CDH1 (OR: 17.04, 95% CI: 3.54-82), CHEK2 (OR: 2.93, 95% CI: 2.29-3.75), PALB2 (OR: 9.53, 95% CI: 6.25-14.51), and TP53 (OR: 7.30, 95% CI: 1.22-43.68). NBN germ line mutations were not significantly associated with BC risk (OR: 1.39, 95% CI: 0.73-2.64). Due to their low mutation prevalence, the RAD51C and RAD51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK2 and TP53 in BC index patients. Compared with the overall sample, only TP53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK2, PALB2, and TP53 genes with bilateral BC. Both, ATM and CHEK2, were negatively associated with triple-negative breast cancer (TNBC) and estrogen receptor (ER)-negative tumor phenotypes. A particularly high CHEK2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors.

Published
2018

5. The benzene metabolite para-benzoquinone is genotoxic in human, phorbol-12-acetate-13-myristate induced, peripheral blood mononuclear cells at low concentrations

Author

Ernst Hallier, Dirk Taeger, Angelika Mönnich, Nadine Lichey, Götz A. Westphal, and Jürgen Bünger

Subjects
Adult, Male, Cell Survival, Cytochalasin B, Metabolite, Benzene, para-Benzoquinone, Phorbol-12-acetate-13-myristate, Health, Toxicology and Mutagenesis, Genotoxicity and Carcinogenicity, medicine.disease_cause, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Benzoquinones, Humans, Phytohemagglutinins, Carcinogen, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Micronucleus Tests, biology, Hydroquinone, Dose-Response Relationship, Drug, Mutagenicity Tests, General Medicine, Middle Aged, Molecular biology, Benzoquinone, 3. Good health, chemistry, Biochemistry, 13. Climate action, 030220 oncology & carcinogenesis, Myeloperoxidase, Micronucleus test, Phorbol, biology.protein, Leukocytes, Mononuclear, Tetradecanoylphorbol Acetate, Female, Genotoxicity, Cell Division
Abstract

Benzene is one of the most prominent occupational and environmental pollutants. The substance is a proven human carcinogen that induces hematologic malignancies in humans, probably at even low doses. Yet knowledge of the mechanisms leading to benzene-induced carcinogenesis is still incomplete. Benzene itself is not genotoxic. The generation of carcinogenic metabolites involves the production of oxidized intermediates such as catechol, hydroquinone and para-benzoquinone (p-BQ) in the liver. Further activation to the ultimate carcinogenic intermediates is most probably catalyzed by myeloperoxidase (MPO). Yet the products of the MPO pathway have not been identiWed. If an oxidized benzene metabolite such as p-BQ was actually the precursor for the ultimate carcinogenic benzene metabolite and further activation proceeds via MPO mediated reactions, it should be possible to activate p-BQ to a genotoxic compound in vitro. We tested this hypothesis with phorbol-12-acetate-13- myristate (PMA) activated peripheral blood cells exposed to p-BQ, using the cytokinesis-block micronucleus test. Addition of 20–28 ng/ml PMA caused a signiWcant increase of micronuclei at low and non-cytotoxic p-BQ concentrations between 0.04 and 0.2 g/ml (0.37– 1.85 M). Thus with PMA or p-BQ alone no reproducible elevation of micronuclei was seen up to toxic concentrations. PMA and p-BQ induce micronuclei when administered jointly. Our results add further support to the hypothesis that MPO is a key enzyme in the activation of benzene. peerReviewed

Published
2009

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