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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



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ID: 541906.0, MPI für molekulare Genetik / Research Group Development and Disease
Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity.
Authors:Tchatchou, S.; Riedel, A.; Lyer, S.; Schmutzhard, J.; Strobel-Freidekind, O.; Gronert-Sum, S.; Mietag, C.; D'Amato, M.; Schlehe, B.; Hemminki, K.; Sutter, C.; Ditsch, N.; Blackburn, A.; Hill, L. Z.; Jerry, D. J.; Bugert, P.; Weber, B. H.; Niederacher, D.; Arnold, N.; Varon-Mateeva, R.; Wappenschmidt, B.; Schmutzler, R. K.; Engel, C.; Meindl, A.; Bartram, C. R.; Mollenhauer, J.; Burwinkel, B.
Language:English
Date of Publication (YYYY-MM-DD):2010-01-01
Title of Journal:Human Mutations
Journal Abbrev.:Hum Mutat
Volume:31
Issue / Number:1
Start Page:60
End Page:66
Copyright:© 2009 Wiley-Liss, Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description: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>T, rs2981745, located in the DMBT1 promoter; and DMBT1 c.124A>C, 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.
Free Keywords:DMBT1 gene;
DMBT1 polymorphisms;
breast cancer risk;
risk factor
Comment of the Author/Creator:Correspondence: Sandrine Tchatchou, Helmholtz-University Group Molecular Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Helmholtz-University Group Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany;
2.Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany;
3.Molecular Oncology, Medical Biotechnology Center, Institute for Medical Biology, University of Southern Denmark, Odense, Denmark;
4.Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany;
5.Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden;
6.Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany;
7.Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden;
8.Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany;
9.Department for Obstetrics and Gynaecology, Ludwig Maximilians Universität, Munich, Germany;
10.John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia;
11.Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts; USA;
12.Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-Hessen, University of Heidelberg, Medical Faculty of Mannheim, Mannheim, Germany;
13.Institute of Human Genetics, University of Regensburg, Regensburg, Germany;
14.Division of Molecular Genetics, Department of Gynaecology and Obstetrics, Clinical Center University of Düsseldorf, Düsseldorf, Germany;
15.Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany;
16.Institut für Humangenetik, Charité-Universitätsmedizin Berlin, Berlin, Germany;
17.Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Center of Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany;
18.Department of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
19.Division of Gynecology and Obstetrics, Klinikum rechts der Isaar at the Technical University Munich, Munich, Germany;
20.Pioneer Valley Life Sciences Institute, Springfield, Massachusetts, USA.
Identifiers:ISSN:1059-7794 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/19830809 [ID No:2]
DOI:10.1002/humu.21134 [ID No:3]
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