Stone Jennifer, Dite Gillian S, Gunasekara Anoma, English Dallas R, McCredie Margaret R E, Giles Graham G, Cawson Jennifer N, Hegele Robert A, Chiarelli Anna M, Yaffe Martin J, Boyd Norman F, Hopper John L
Centre for Molecular Environmental Genetic and Analytic Epidemiology, The University of Melbourne, Carlton, Victoria, Australia.
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):612-7. doi: 10.1158/1055-9965.EPI-05-0127.
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.
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.
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.
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.
乳腺钼靶密度百分比（PMD）是乳腺癌的一个风险因素。我们之前的双生子研究表明，PMD的遗传度为63%。本研究确定了PMD各组成部分的遗传度，即乳腺钼靶片中致密组织和非致密组织的面积。
我们合并了两项双生子研究，其中包括从澳大利亚和北美招募的571对同卵双生子和380对异卵双生子。使用计算机辅助方法测量致密和非致密区域，并通过问卷获取有关潜在决定因素的信息。在经典双生子模型的假设下，我们使用最大似然理论和统计软件包FISHER估计了对数致密面积和对数非致密面积的遗传度，以及这两个性状之间协方差的遗传和环境贡献。
在对测量的决定因素进行调整后，对于对数致密面积和对数非致密面积中的每一个，同卵双生子的相关性均大于异卵双生子的相关性。致密面积的遗传度估计为65%（95%置信区间，60 - 70%），非致密面积的遗传度估计为66%（95%置信区间，61 - 71%）。同一受试者中两个调整后性状之间的相关性（标准误）为 -0.35（0.023），同卵双生子对之间为 -0.26（0.026），异卵双生子对之间为 -0.14（0.034）。
遗传因素可能在解释致密组织和非致密组织的乳腺钼靶面积变异中起很大作用。致密和非致密面积之间约三分之二的负相关性是由影响这两个性状但方向相反的相同遗传因素所解释的。
