title: Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures.
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.
authors: Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, Western Australia, Australia.
authors: Jennifer
authors: J
authors: Stone
authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Deborah J
authors: DJ
authors: Thompson
authors: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Isabel
authors: I
authors: Dos Santos Silva
authors: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors: Christopher
authors: C
authors: Scott
authors: 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.
authors: Rulla M
authors: RM
authors: Tamimi
authors: 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.
authors: Sara
authors: S
authors: Lindstrom
authors: 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.
authors: Peter
authors: P
authors: Kraft
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors: Aditi
authors: A
authors: Hazra
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors: Jingmei
authors: J
authors: Li
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Louise
authors: L
authors: Eriksson
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Kamila
authors: K
authors: Czene
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Per
authors: P
authors: Hall
authors: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors: Matt
authors: M
authors: Jensen
authors: Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors: Julie
authors: J
authors: Cunningham
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
authors: Janet E
authors: JE
authors: Olson
authors: Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan.
authors: Kristen
authors: K
authors: Purrington
authors: 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.
authors: Fergus J
authors: FJ
authors: Couch
authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Judith
authors: J
authors: Brown
authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Jean
authors: J
authors: Leyland
authors: Department of Radiology, University of Cambridge, Addenbrooke's NHS Foundation Trust, Cambridge, United Kingdom.
authors: Ruth M L
authors: RM
authors: Warren
authors: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Robert N
authors: RN
authors: Luben
authors: MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival (CNC), University of Cambridge, Cambridge, United Kingdom.
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors: Paula
authors: P
authors: Smith
authors: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors: Nicholas J
authors: NJ
authors: Wareham
authors: 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.
authors: Sebastian M
authors: SM
authors: Jud
authors: 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.
authors: Katharina
authors: K
authors: Heusinger
authors: 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.
authors: Matthias W
authors: MW
authors: Beckmann
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Julie A
authors: JA
authors: Douglas
authors: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Kaanan P
authors: KP
authors: Shah
authors: Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Heang-Ping
authors: HP
authors: Chan
authors: Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Mark A
authors: MA
authors: Helvie
authors: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors: Loic
authors: L
authors: Le Marchand
authors: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors: Laurence N
authors: LN
authors: Kolonel
authors: Department of Obstetrics and Genecology, IWK Health Centre, Halifax, Canada.
authors: Christy
authors: C
authors: Woolcott
authors: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors: Gertraud
authors: G
authors: Maskarinec
authors: Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Christopher
authors: C
authors: Haiman
authors: 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.
authors: Graham G
authors: GG
authors: Giles
authors: 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.
authors: Laura
authors: L
authors: Baglietto
authors: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors: Kavitha
authors: K
authors: Krishnan
authors: Department of Pathology, University of Melbourne, Melbourne, Australia.
authors: Melissa C
authors: MC
authors: Southey
authors: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors: Carmel
authors: C
authors: Apicella
authors: Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Irene L
authors: IL
authors: Andrulis
authors: 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.
authors: Julia A
authors: JA
authors: Knight
authors: Institute of Basic Medical Sciences, University of Oslo, Norway. Department of Preventive Medicine, University of Southern California, California.
authors: Giske
authors: G
authors: Ursin
authors: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors: Grethe I Grenaker
authors: GI
authors: Alnaes
authors: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors: Vessela N
authors: VN
authors: Kristensen
authors: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors: Anne-Lise
authors: AL
authors: Borresen-Dale
authors: Faculty of Health Sciences, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors: Inger Torhild
authors: IT
authors: Gram
authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Manjeet K
authors: MK
authors: Bolla
authors: Faculty of Health Sciences, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors: Qin
authors: Q
authors: Wang
authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Kyriaki
authors: K
authors: Michailidou
authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: Joe
authors: J
authors: Dennis
authors: Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec, Canada.
authors: Jacques
authors: J
authors: Simard
authors: 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.
authors: Paul
authors: P
authors: Pharoah
authors: Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
authors: Alison M
authors: AM
authors: Dunning
authors: 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.
authors: Douglas F
authors: DF
authors: Easton
authors: 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.
authors: Peter A
authors: PA
authors: Fasching
authors: Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors: V Shane
authors: VS
authors: Pankratz
authors: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors: John L
authors: JL
authors: Hopper
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota. vachon.celine@mayo.edu.
authors: Celine M
authors: CM
authors: Vachon
mesh_terms: D000368:Aged; D000071060:Breast Density; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities* / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors