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159 Publications visible to you, out of a total of 159
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for … homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia-like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the ’common disease, rare allele’ hypothesis.

Authors: Alfons Meindl, Heide Hellebrand, Constanze Wiek, Verena Erven, Barbara Wappenschmidt, Dieter Niederacher, Marcel Freund, Peter Lichtner, Linda Hartmann, Heiner Schaal, Juliane Ramser, Ellen Honisch, Christian Kubisch, Hans E. Wichmann, Karin Kast, Helmut Deissler, Christoph Engel, Bertram Müller-Myhsok, Kornelia Neveling, Marion Kiechle, Christopher G. Mathew, Detlev Schindler, Rita K. Schmutzler, Helmut Hanenberg

Date Published: 1st May 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

A BRCA1 promoter variant (rs11655505) and breast cancer risk
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND A study of Chinese women recently suggested that the minor allele of rs11655505 in the BRCA1 promoter (c.-2265C–\textgreaterT) increases promoter activity and has a protective effect on …n breast cancer risk. METHODS We genotyped rs11655505 in 2912 female breast cancer cases and 2783 unaffected female controls from four Caucasian breast cancer studies. RESULTS No evidence for an association between rs11655505 and breast cancer risk was found. CONCLUSIONS Our study failed to confirm a role of rs11655505 in breast cancer risk. Larger studies are necessary to determine if there is a weak association between this SNP and breast cancer risk.

Authors: Paolo Verderio, Sara Pizzamiglio, Melissa C. Southey, Amanda B. Spurdle, John L. Hopper, Xiaoqing Chen, Jonathan Beesley, Rita K. Schmutzler, Christoph Engel, Barbara Burwinkel, Peter Bugert, Filomena Ficarazzi, Siranoush Manoukian, Monica Barile, Barbara Wappenschmidt, Georgia Chenevix-Trench, Paolo Radice, Paolo Peterlongo

Date Published: 22nd Apr 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Practice of volume therapy in patients with severe sepsis: results from a nationwide sepsis prevalence study
SepNet - German Competence Network Sepsis

Abstract

Not specified

Authors: Christiane S. Hartog, Frank M. Brunkhorst, Frank Bloos, Holger Bogatsch, Christoph Engel, Kerstin Sengebusch, Konrad Reinhart, Maximilian Ragaller

Date Published: 1st Mar 2010

Publication Type: Journal article

Human Diseases: disease by infectious agent

Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. … Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C\textgreaterT, rs2981745, located in the DMBT1 promoter; and DMBT1 c.124A\textgreaterC, p.Thr42Pro, rs11523871(odds ratio [OR]=1.66, 95% confidence interval [CI]=1.21-2.29, P=0.0017; and OR=1.66; 95% CI=1.21-2.28, P=0.0016, respectively), based on 1,195 BRCA1/2 mutation-negative German breast cancer families and 1,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5’-region are associated with increased breast cancer risk. In accordance with previous results, these data link decreased DMBT1 levels to breast cancer risk.

Authors: Sandrine Tchatchou, Angela Riedel, Stefan Lyer, Julia Schmutzhard, Olga Strobel-Freidekind, Sabine Gronert-Sum, Carola Mietag, Mauro D’Amato, Bettina Schlehe, Kari Hemminki, Christian Sutter, Nina Ditsch, Anneke Blackburn, Linda Zhai Hill, D. Joseph Jerry, Peter Bugert, Bernhard H. F. Weber, Dieter Niederacher, Norbert Arnold, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Rita K. Schmutzler, Christoph Engel, Alfons Meindl, Claus R. Bartram, Jan Mollenhauer, Barbara Burwinkel

Date Published: 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Low-risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

To validate common low-risk variants predisposing for breast cancer (BC) in a large set of BRCA1/2 negative familial or genetically enriched cases from Germany, we genotyped 1,415 cases and 1,830 healthy … women by MALDI-TOF in 105 candidate SNPs. Significantly higher ORs than previously reported for heterozygous unselected cases were found for the minor allele in FGFR2 (OR = 1.43, 95% CI 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% CI 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% CI 1.68-2.51, LSP1 (OR = 0.49, 95% CI 0.28-0.86) and TNRC9 (OR = 1.62, 95% CI 1.27-2.07). Moreover, the additional validation of 99 CGEMS-SNPs identified putative novel susceptibility alleles within the LSP1 gene (OR = 0.73, 95% CI 0.61-0.87, p-value = 5.23 x 10(-4)). Finally, we provide evidence for the first time that a low-risk variant located at 6q22.33 (rs6569479) is associated with estrogen receptor negative BC in familial cases (OR = 1.33, 95% CI 1.06-1.66; p-value = 0.012). Our data confirm the impact of the previously identified susceptibility loci and provide preliminary evidence for novel susceptibility loci in familial BC cases and correlate them to specific histopathological subtypes defined by estrogen receptor status.

Authors: Kari Hemminki, Bertram Müller-Myhsok, Peter Lichtner, Christoph Engel, Bowang Chen, Barbara Burwinkel, Asta Försti, Christian Sutter, Barbara Wappenschmidt, Heide Hellebrand, Thomas Illig, Norbert Arnold, Dieter Niederacher, Bernd Dworniczak, Helmut Deissler, Karin Kast, Dorothea Gadzicki, Thomas Meitinger, H-Erich Wichmann, Marion Kiechle, Claus R. Bartram, Rita K. Schmutzler, Alfons Meindl

Date Published: 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

PURPOSE To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors. PATIENTS AND METHODS A retrospective, multicenter, …er, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene. RESULTS The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer. CONCLUSION Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.

Authors: Monika K. Graeser, Christoph Engel, Kerstin Rhiem, Dorothea Gadzicki, Ulrich Bick, Karin Kast, Ursula G. Froster, Bettina Schlehe, Astrid Bechtold, Norbert Arnold, Sabine Preisler-Adams, Carolin Nestle-Kraemling, Mohammad Zaino, Markus Loeffler, Marion Kiechle, Alfons Meindl, Dominic Varga, Rita K. Schmutzler

Date Published: 10th Dec 2009

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general …l population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. METHODS We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. RESULTS We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. CONCLUSION This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

Authors: A. Osorio, R. L. Milne, G. Pita, P. Peterlongo, T. Heikkinen, J. Simard, G. Chenevix-Trench, A. B. Spurdle, J. Beesley, X. Chen, S. Healey, S. L. Neuhausen, Y. C. Ding, F. J. Couch, X. Wang, N. Lindor, S. Manoukian, M. Barile, A. Viel, L. Tizzoni, C. I. Szabo, L. Foretova, M. Zikan, K. Claes, M. H. Greene, P. Mai, G. Rennert, F. Lejbkowicz, O. Barnett-Griness, I. L. Andrulis, H. Ozcelik, N. Weerasooriya, A-M Gerdes, M. Thomassen, D. G. Cruger, M. A. Caligo, E. Friedman, B. Kaufman, Y. Laitman, S. Cohen, T. Kontorovich, R. Gershoni-Baruch, E. Dagan, H. Jernström, M. S. Askmalm, B. Arver, B. Malmer, S. M. Domchek, K. L. Nathanson, J. Brunet, T. Ramón Y Cajal, D. Yannoukakos, U. Hamann, F. B. L. Hogervorst, S. Verhoef, E. B. Gómez García, J. T. Wijnen, A. van den Ouweland, D. F. Easton, S. Peock, M. Cook, C. T. Oliver, D. Frost, C. Luccarini, D. G. Evans, F. Lalloo, R. Eeles, G. Pichert, J. Cook, S. Hodgson, P. J. Morrison, F. Douglas, A. K. Godwin, O. M. Sinilnikova, L. Barjhoux, D. Stoppa-Lyonnet, V. Moncoutier, S. Giraud, C. Cassini, L. Olivier-Faivre, F. Révillion, J-P Peyrat, D. Muller, J-P Fricker, H. T. Lynch, E. M. John, S. Buys, M. Daly, J. L. Hopper, M. B. Terry, A. Miron, Y. Yassin, D. Goldgar, C. F. Singer, D. Gschwantler-Kaulich, G. Pfeiler, A-C Spiess, Thomas v. O. Hansen, O. T. Johannsson, T. Kirchhoff, K. Offit, K. Kosarin, M. Piedmonte, G. C. Rodriguez, K. Wakeley, J. F. Boggess, J. Basil, P. E. Schwartz, S. V. Blank, A. E. Toland, M. Montagna, C. Casella, E. N. Imyanitov, A. Allavena, R. K. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Ditsch, N. Arnold, D. Niederacher, H. Deissler, B. Fiebig, R. Varon-Mateeva, D. Schaefer, U. G. Froster, T. Caldes, M. de La Hoya, L. McGuffog, A. C. Antoniou, H. Nevanlinna, P. Radice, J. Benítez

Date Published: 1st Dec 2009

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

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