Volumetric mammographic density: heritability and association with breast cancer susceptibility loci

Judith S Brand, Keith Humphreys, Deborah J Thompson, Jingmei Li, Mikael Eriksson, Per Hall, Kamila Czene

Research output: Contribution to journalArticle (Academic Journal)

13 Citations (Scopus)

Abstract

BACKGROUND: Mammographic density is a strong heritable trait, but data on its genetic component are limited to area-based and qualitative measures. We studied the heritability of volumetric mammographic density ascertained by a fully-automated method and the association with breast cancer susceptibility loci.

METHODS: Heritability of volumetric mammographic density was estimated with a variance component model in a sib-pair sample (N pairs = 955) of a Swedish screening based cohort. Associations with 82 established breast cancer loci were assessed in an independent sample of the same cohort (N = 4025 unrelated women) using linear models, adjusting for age, body mass index, and menopausal status. All tests were two-sided, except for heritability analyses where one-sided tests were used.

RESULTS: After multivariable adjustment, heritability estimates (standard error) for percent dense volume, absolute dense volume, and absolute nondense volume were 0.63 (0.06) and 0.43 (0.06) and 0.61 (0.06), respectively (all P < .001). Percent and absolute dense volume were associated with rs10995190 (ZNF365; P = 9.0 × 10(-6) and 8.9 × 10(-7), respectively) and rs9485372 (TAB2; P = 1.8 × 10(-5) and 1.8 × 10(-3), respectively). We also observed associations of rs9383938 (ESR1) and rs2046210 (ESR1) with the absolute dense volume (P = 2.6 × 10(-4) and 4.6 × 10(-4), respectively), and rs6001930 (MLK1) and rs17356907 (NTN4) with the absolute nondense volume (P = 6.7 × 10(-6) and 8.4 × 10(-5), respectively).

CONCLUSIONS: Our results support the high heritability of mammographic density, though estimates are weaker for absolute than percent dense volume. We also demonstrate that the shared genetic component with breast cancer is not restricted to dense tissues only.

Original languageEnglish
Article numberdju334
JournalJournal of the National Cancer Institute
Volume106
Issue number12
Early online date5 Nov 2014
DOIs
Publication statusPublished - Dec 2014

Keywords

  • Adult
  • Aged
  • Breast Density
  • Breast Neoplasms
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Linear Models
  • Mammary Glands, Human
  • Mammography
  • Middle Aged
  • Organ Size
  • Polymorphism, Single Nucleotide
  • Journal Article
  • Research Support, Non-U.S. Gov't

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