The heritability of mammographically dense and nondense breast tissue.
BACKGROUND
Percent mammographic density (PMD) is a risk factor for breast cancer. Our previous twin study showed that the heritability of PMD was 63%. This study determined the heritabilities of the components of PMD, the areas of dense and nondense tissue in the mammogram.


METHODS
We combined two twin studies comprising 571 monozygous and 380 dizygous twin pairs recruited from Australia and North America. Dense and nondense areas were measured using a computer-assisted method, and information about potential determinants was obtained by questionnaire. Under the assumptions of the classic twin model, we estimated the heritability of the log dense area and log nondense area and the genetic and environmental contributions to the covariance between the two traits, using maximum likelihood theory and the statistical package FISHER.


RESULTS
After adjusting for measured determinants, for each of the log dense area and the log nondense area, the monozygous correlations were greater than the dizygous correlations. Heritability was estimated to be 65% (95% confidence interval, 60-70%) for dense area and 66% (95% confidence interval, 61-71%) for nondense area. The correlations (SE) between the two adjusted traits were -0.35 (0.023) in the same individual, -0.26 (0.026) across monozygous pairs, and -0.14 (0.034) across dizygous pairs.


CONCLUSIONS
Genetic factors may play a large role in explaining variation in the mammographic areas of both dense and nondense tissue. About two thirds of the negative correlation between dense and nondense area is explained by the same genetic factors influencing both traits, but in opposite directions.
Stone
Jennifer
J
Centre for Molecular Environmental Genetic and Analytic Epidemiology, The University of Melbourne, Carlton, Victoria, Australia. j.stone3@pgrad.unimelb.edu.au
Dite
Gillian S
GS
Gunasekara
Anoma
A
English
Dallas R
DR
McCredie
Margaret R E
MR
Giles
Graham G
GG
Cawson
Jennifer N
JN
Hegele
Robert A
RA
Chiarelli
Anna M
AM
Yaffe
Martin J
MJ
Boyd
Norman F
NF
Hopper
John L
JL
D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000328:Adult; D000367:Age Factors; D000368:Aged; 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