Article
PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
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- (1) Karolinska Institute, grid.4714.6
- (2) Uppsala University, grid.8993.b
- (3) Cyprus Institute of Neurology and Genetics, grid.417705.0
- (4) University of Cambridge, grid.5335.0
- (5) Roswell Park Cancer Institute, grid.240614.5
- (6) Mount Sinai Hospital, grid.416166.2
- (7) University of Toronto, grid.17063.33
- (8) University of California, Irvine, grid.266093.8
- (9) 10, N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
- (10) German Cancer Research Center, grid.7497.d
- (11) 12, Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- (12) 13, Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (13) International Epidemiology Institute, grid.419344.f
- (14) 14, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- (15) Flanders Institute for Biotechnology, grid.11486.3a
- (16) KU Leuven, grid.5596.f
- (17) 18, Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (18) 19, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (19) University of Copenhagen, grid.5254.6, KU
- (20) European Institute of Oncology, grid.15667.33
- (21) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
- (22) University of Tübingen, grid.10392.39
- (23) Antoni van Leeuwenhoek Hospital, grid.430814.a
- (24) Ruhr University Bochum, grid.5570.7
- (25) Heidelberg University, grid.7700.0
- (26) University Cancer Center Hamburg, grid.412315.0
- (27) Mayo Clinic, grid.66875.3a
- (28) University of Sheffield, grid.11835.3e
- (29) Leiden University Medical Center, grid.10419.3d
- (30) London School of Hygiene & Tropical Medicine, grid.8991.9
- (31) Hannover Medical School, grid.10423.34
- (32) University of California, Los Angeles, grid.19006.3e
- (33) University of Edinburgh, grid.4305.2
- (34) National Cancer Institute, grid.48336.3a
- (35) University Medical Center Hamburg-Eppendorf, grid.13648.38
- (36) 60, Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- (37) University of Melbourne, grid.1008.9
- (38) Cancer Council Victoria, grid.3263.4
- (39) Spanish National Cancer Research Centre, grid.7719.8
- (40) 64, Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
- (41) University of Southern California, grid.42505.36
- (42) Erasmus University Medical Center, grid.5645.2
- (43) Pomeranian Medical University, grid.107950.a
- (44) Institute of Cancer Research, grid.18886.3f
- (45) National University of Ireland, Galway, grid.6142.1
- (46) Kuopio University Hospital, grid.410705.7
- (47) University of Eastern Finland, grid.9668.1
- (48) 41, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- (49) 42, Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
- (50) Oslo University Hospital, grid.55325.34
- (51) University of Hawaii at Manoa, grid.410445.0
- (52) Technical University of Munich, grid.6936.a
- (53) University Health Network, grid.231844.8
- (54) City Of Hope National Medical Center, grid.410425.6
- (55) 82, Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
- (56) 84, Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
- (57) University of Oulu, grid.10858.34
- (58) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
- (59) King's College London, grid.13097.3c
- (60) University Hospital Cologne, grid.411097.a
- (61) University of Cologne, grid.6190.e
- (62) Laval University, grid.23856.3a
- (63) 96, Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
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Description
Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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