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

Journal article

Publication Details

Author(s): Stone J, Thompson DJ, Silva IDS, Scott C, Tamimi RM, Lindstrom S, Kraft P, Hazra A, Li J, Eriksson L, Czene K, Hall P, Jensen M, Cunningham J, Olson JE, Purrington K, Couch FJ, Brown J, Leyland J, Warren RML, Luben RN, Khaw KT, Smith P, Wareham NJ, Jud S, Heusinger K, Beckmann M, Douglas JA, Shah KP, Chan HP, Helvie MA, Le Marchand L, Kolonel LN, Woolcott C, Maskarinec G, Haiman C, Giles GG, Baglietto L, Krishnan K, Southey MC, Apicella C, Andrulis IL, Knight JA, Ursin G, Alnaes GIG, Kristensen VN, Borresen-Dale AL, Gram IT, Bolla MK, Wang Q, Michailidou K, Dennis J, Simard J, Pharoah P, Dunning AM, Easton DF, Fasching P, Pankratz VS, Hopper JL, Vachon CM
Journal: Cancer Research
Publication year: 2015
Volume: 75
Journal issue: 12
Pages range: 2457-67
ISSN: 0008-5472


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.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Jud, Sebastian Dr.

External institutions with authors

Brigham and Women's Hospital (BWH)
Cancer Council Victoria
Centre hospitalier universitaire de Québec
Dalhousie University
Harvard University
Karolinska Institute
London School of Hygiene and Tropical Medicine
Mayo Clinic
Mount Sinai Hospital (MSH)
Oslo University Hospital / Oslo Universitetssykehus
The University of Melbourne
University of Cambridge
University of Hawaii (U.H.)
University of Michigan
University of Oslo
University of Southern California (USC)
University of Tromsø
University of Western Australia (UWA)
Wayne State University (WSU)

How to cite

Stone, J., Thompson, D.J., Silva, I.D.S., Scott, C., Tamimi, R.M., Lindstrom, S.,... Vachon, C.M. (2015). Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures. Cancer Research, 75(12), 2457-67.

Stone, Jennifer, et al. "Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures." Cancer Research 75.12 (2015): 2457-67.


Last updated on 2019-21-07 at 07:53