Ursin Giske, Lillie Elizabeth O, Lee Eunjung, Cockburn Myles, Schork Nicholas J, Cozen Wendy, Parisky Yuri R, Hamilton Ann S, Astrahan Melvin A, Mack Thomas
Department of Preventive Medicine, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):102-12. doi: 10.1158/1055-9965.EPI-07-2857.
Although several environmental factors predict mammographic density, estimates of its heritability have been quite high. We investigated whether part of the presumed heritability might be attributed to differential sharing of modifiable risk factors in monozygotic (MZ) and dizygotic (DZ) twins.
We measured percent and absolute mammographic density using mammograms from 257 MZ and 296 DZ twin pairs. The correlation of intrapair mammographic density was compared according to zygosity across strata of modifiable risk factors. Portions of variance attributable to additive genetic factors, shared environment, and individual environment were calculated using a variance component methodology in the entire set, and within twin pairs stratified by environmental trait similarity.
Both percent density and absolute mammographic density were more highly correlated between MZ twins than DZ twins, but the correlations varied across strata. Body mass index (BMI) and parity strongly predicted differences in mammographic density within MZ twin pairs. After adjusting for covariates, 53% of the total variance in percent density and 59% of that in absolute density seemed attributable to genetic effects, but these estimates varied greatly by stratum. For twins dissimilar on BMI (difference >2.5 kg/m(2)), the additive genetic component of absolute density was estimated at only 20% (+/-19%), and the common and individual environment at 21% (+/-14%) and 49%, respectively (P value for heterogeneity across BMI = 0.0001).
Our results confirm that the genome is an important determinant of mammographic density but suggest that an unknown portion of the mammographic density effect attributed to the genome may be due to shared modifiable environmental factors.
尽管有多种环境因素可预测乳腺X线密度，但其遗传度估计值一直很高。我们研究了假定遗传度的部分原因是否可能归因于同卵（MZ）和异卵（DZ）双胞胎中可改变风险因素的差异共享。
我们使用257对MZ和296对DZ双胞胎的乳腺X线照片测量了乳腺X线密度百分比和绝对密度。根据可改变风险因素分层的合子性比较了双胞胎对中乳腺X线密度的相关性。使用方差成分法在整个样本集以及按环境特征相似性分层的双胞胎对中计算了归因于加性遗传因素、共享环境和个体环境的方差部分。
MZ双胞胎之间的密度百分比和绝对乳腺X线密度的相关性均高于DZ双胞胎，但相关性在各层中有所不同。体重指数（BMI）和产次强烈预测了MZ双胞胎对中乳腺X线密度的差异。在调整协变量后，密度百分比总方差的53%和绝对密度总方差的59%似乎归因于遗传效应，但这些估计值在各层中差异很大。对于BMI不同（差异>2.5kg/m²）的双胞胎，绝对密度的加性遗传成分估计仅为20%（±19%），共同环境和个体环境分别为21%（±14%）和49%（BMI异质性的P值 = 0.0001）。
我们的结果证实基因组是乳腺X线密度的重要决定因素，但表明归因于基因组的乳腺X线密度效应中未知部分可能是由于共享的可改变环境因素。
