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BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
H. Shimelis, RLS. Mesman, C. Von Nicolai, A. Ehlen, L. Guidugli, C. Martin, FMGR. Calléja, H. Meeks, E. Hallberg, J. Hinton, J. Lilyquist, C. Hu, CM. Aalfs, K. Aittomäki, I. Andrulis, H. Anton-Culver, V. Arndt, MW. Beckmann, J. Benitez, NV....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Perzistentní odkaz
https://www.medvik.cz/link/bmc17030972
Online
Plný text
NLK
Free Medical Journals
od 1941 do Před 1 rokem
Freely Accessible Science Journals
od 1941 do Před 1 rokem
Open Access Digital Library
od 1941-01-01
Open Access Digital Library
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- MeSH
- genotyp MeSH
- lidé MeSH
- missense mutace MeSH
- myši MeSH
- nádory prsu genetika MeSH
- protein BRCA2 genetika MeSH
- riziko MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- substituce aminokyselin MeSH
- zárodečné mutace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR.
Cancer Control and Population Sciences University of Utah Salt Lake City Utah
Center for Medical Genetics Ghent University Hospita Ghent Belgium
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Genetics Erasmus University Medical Center Rotterdam the Netherlands
Department of Clinical Genetics Helsinki University Hospital University of Helsinki Helsinki Finland
Department of Clinical Genetics Leiden University Medical Center Leiden the Netherlands
Department of Epidemiology University of California Irvine Irvine California
Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland
Department of Genetics University of Groningen Groningen the Netherlands
Department of Health Sciences Research Mayo Clinic Rochester Minnesota
Department of Human Genetics Leiden University Medical Center Leiden the Netherlands
Department of Human Genetics University of Chicago Chicago Illinois
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
Department of Oncology Pathology Karolinska Institutet Stockholm Sweden
Department of Oncology University of Cambridge Cambridge United Kingdom
Department of Pathology The University of Melbourne Melbourne Australia
Department of Pathology University of Otago Christchurch New Zealand
Department of Population Sciences Beckman Research Institute of City of Hope Duarte California
Department of Public Health and Primary Care University of Cambridge Cambridge United Kingdom
Department of Surgery National Taiwan University Hospital Taipei Taiwan
Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville Maryland
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of Health Sciences Warwick Medical School Warwick University Coventry United Kingdom
Genotoxic Stress and Cancer Institut Curie Orsay France
Gynaecology Research Unit Hannover Medical School Hannover Germany
Huntsman Cancer Institute and Department of Dermatology University of Utah Salt Lake City Utah
IFOM The FIRC Institute of Molecular Oncology Milan Italy
International Agency for Research on Cancer Lyon France
Lunenfeld Tanenbaum Research Institute of Mount Sinai Hospital Toronto Canada
Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany
National Cancer Institute Bangkok Thailand
Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam the Netherlands
Research Center Institute Curie Orsay France
Research Oncology Guy's Hospital King's College London London United Kingdom
Saw Swee Hock School of Public Health National University of Singapore Singapore Singapore
Shanghai Municipal Center for Disease Control and Prevention Shanghai China
Singapore Eye Research Institute National University of Singapore Singapore Singapore
Unit of Hereditary Cancers IRCCS AOU San Martino Genova Italy
University of Hawaii Cancer Center Honolulu Hawaii
Westmead Millenium Institute for Medical Research University of Sydney Sydney Australia
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- $a Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR.
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- $a Torres, Diana $u Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
- 700 1_
- $a Truong, Thérèse $u Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
- 700 1_
- $a van Asperen, Christi J $u Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
- 700 1_
- $a van der Kolk, Lizet E $u Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
- 700 1_
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- 700 1_
- $a Winqvist, Robert $u Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland. Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Monteiro, Alvaro N A $u Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Department of Oncologic Science, University of South Florida, Tampa, Florida.
- 700 1_
- $a Goldgar, David E $u Huntsman Cancer Institute and Department of Dermatology, University of Utah, Salt Lake City, Utah.
- 700 1_
- $a Carreira, Aura $u Genotoxic Stress and Cancer, Institut Curie, Orsay, France.
- 700 1_
- $a Vreeswijk, Maaike P G $u Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
- 700 1_
- $a Couch, Fergus J $u Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. couch.fergus@mayo.edu. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
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