Mammographic Density and Candidate Gene Variants: A Twins and Sisters Study

Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1479-84. doi: 10.1158/1055-9965.EPI-07-0107.

Abstract

Background: Mammographic density, the light/white radiographic appearance on a mammogram that represents connective and epithelial tissue, is a strong risk factor for breast cancer which seems to be highly heritable. Little is known about its genetic determinants.

Methods: We studied 457 women from 207 sisterhoods (104 monozygotic twins, 182 dizygotic twins, and 171 singletons). Percentage mammographic density (PMD) as well as dense area and nondense area were calculated using a computer-assisted method. We measured six single nucleotide polymorphisms from six candidate genes (COMT, HSD3B1, IGFBP3, HER2, XPD, and XRCC3). Associations between genotypes and mammographic measures were tested (a) cross-sectionally using a multivariate normal model fitted using FISHER that allowed separate correlations for monozygotic, dizygotic, and nontwin pairs and (b) within sister pairs using paired t tests.

Results: Cross-sectionally, each additional copy of the HSD3B1 Asn(367)Thr variant allele was associated with lower PMD (-3.47% per allele; SE = 1.65; P = 0.035). Within-pair regression estimates confirmed this association. There was no evidence for an association between the mammographic density measures and any of the other variants studied.

Conclusion: We have replicated an association between a variant in the HSD3B1 gene and PMD, which suggests that HSD3B1 may be genetic determinant of mammographic density.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / genetics
  • Adult
  • Aged
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / genetics*
  • Catechol O-Methyltransferase / genetics
  • Cohort Studies
  • Cross-Sectional Studies
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Variation*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Mammography*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Receptor, ErbB-2 / genetics
  • Siblings*
  • Twins, Dizygotic / genetics*
  • Twins, Monozygotic / genetics*
  • Xeroderma Pigmentosum Group D Protein / genetics

Substances

  • DNA-Binding Proteins
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Neoplasm Proteins
  • X-ray repair cross complementing protein 3
  • 3-Hydroxysteroid Dehydrogenases
  • Catechol O-Methyltransferase
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human