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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Density
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Disease Susceptibility
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Mammary Glands, Human / abnormalities*
  • Mammary Glands, Human / pathology
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors

Grant support