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Cancer Res. 2015 Jun 15;75(12):2457-67. doi: 10.1158/0008-5472.CAN-14-2012. Epub 2015 Apr 10.

Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures.

Author information

1
Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia.
2
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
3
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
4
Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minnesota.
5
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
6
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts.
7
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
8
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
9
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
10
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
11
Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
12
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
13
Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan.
14
Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota. Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
15
Department of Radiology, University of Cambridge, Addenbrooke's NHS Foundation Trust, Cambridge, United Kingdom.
16
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
17
MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), University of Cambridge, Cambridge, United Kingdom.
18
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
19
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
20
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg, Erlangen-Nuremberg, Germany.
21
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan.
22
Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan.
23
University of Hawaii Cancer Center, Honolulu, Hawaii.
24
Department of Obstetrics and Genecology, IWK Health Centre, Halifax, Canada.
25
Keck School of Medicine, University of Southern California, Los Angeles, California.
26
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
27
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. Centre for Research in Epidemiology and Population Health, Gustave Roussy Institute, Villejuif Cedex, France. Paris-South University, Villejuif, France.
28
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
29
Department of Pathology, University of Melbourne, Melbourne, Australia.
30
Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
31
Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
32
Institute of Basic Medical Sciences, University of Oslo, Norway. Department of Preventive Medicine, University of Southern California, California.
33
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
34
Faculty of Health Sciences, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
35
Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec, Canada.
36
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
37
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
38
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg, Erlangen-Nuremberg, Germany. Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
39
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota. vachon.celine@mayo.edu.

Abstract

Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P < 10(-5)). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk.

PMID:
25862352
PMCID:
PMC4470785
DOI:
10.1158/0008-5472.CAN-14-2012
[Indexed for MEDLINE]
Free PMC Article

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