title: Heritability of mammographic density, a risk factor for breast cancer.
abstract: BACKGROUND
  Women with extensive dense breast tissue visible on a mammogram have a risk of breast cancer that is 1.8 to 6.0 times that of women of the same age with little or no density. Menopausal status, weight, and parity account for 20 to 30 percent of the age-adjusted variation in the percentage of dense tissue.
  
  
  METHODS
  We undertook two studies of twins to determine the proportion of the residual variation in the percentage of density measured by mammography that can be explained by unmeasured additive genetic factors (heritability). A total of 353 pairs of monozygotic twins and 246 pairs of dizygotic twins were recruited from the Australian Twin Registry, and 218 pairs of monozygotic twins and 134 pairs of dizygotic twins were recruited in Canada and the United States. Information on putative determinants of breast density was obtained by questionnaire. Mammograms were digitized, randomly ordered, and read by a blinded investigator.
  
  
  RESULTS
  After adjustment for age and measured covariates, the correlation coefficient for the percentage of dense tissue was 0.61 for monozygotic pairs in Australia, 0.67 for monozygotic pairs in North America, 0.25 for dizygotic pairs in Australia, and 0.27 for dizygotic pairs in North America. According to the classic twin model, heritability (the proportion of variants attributable to additive genetic factors) accounted for 60 percent of the variation in density (95 percent confidence interval, 54 to 66) in Australian twins, 67 percent (95 percent confidence interval, 59 to 75) in North American twins, and 63 percent (95 percent confidence interval, 59 to 67) in all twins studied.
  
  
  CONCLUSIONS
  These results show that the population variation in the percentage of dense tissue on mammography at a given age has high heritability. Because mammographic density is associated with an increased risk of breast cancer, finding the genes responsible for this phenotype could be important for understanding the causes of the disease.
authors.affiliation: Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada. boyd@uhnres.utoronto.ca
authors.forename: Norman F
authors.initials: NF
authors.lastname: Boyd
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dite
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stone
authors.forename: Anoma
authors.initials: A
authors.lastname: Gunasekara
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.forename: Margaret R E
authors.initials: MR
authors.lastname: McCredie
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: David
authors.initials: D
authors.lastname: Tritchler
authors.forename: Anna
authors.initials: A
authors.lastname: Chiarelli
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Yaffe
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001940:Breast / Q000033:anatomy & histology*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D012307:Risk Factors; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics