Mammographic breast density--evidence for genetic correlations with established breast cancer risk factors.
Mammographic breast density--evidence for genetic correlations with established breast cancer risk factors.
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乳房 X 光检查乳腺密度——与已确定的乳腺癌危险因素遗传相关的证据。
DOI：
10.1158/1055-9965.epi-08-0480
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Helvie MA
中科院分区：
文献类型：
--
作者：
Douglas JA;Roy-Gagnon MH;Zhou C;Mitchell BD;Shuldiner AR;Chan HP;Helvie MA
以前的双胞胎和家庭研究表明，乳腺密度的家庭聚集是由于（部分）遗传因素。然而，这些遗传影响是否与其他乳腺癌风险因素共享尚不清楚。使用标准的电影屏幕乳房X光检查，我们筛选了550名妇女，包括611对姐妹篇，从旧秩序阿米什人口的兰开斯特县，宾夕法尼亚州。我们将乳房X线照片数字化，并使用计算机辅助方法量化乳房的致密和非致密区域。通过问卷调查和体格检查收集其他乳腺癌危险因素的信息，使用基于家系的方差分量法，我们估计了几个乳腺癌危险因素的遗传贡献，包括乳房密度，并评估了它们之间共享遗传影响的证据。调整协变量后，遗传效应占每个风险因素总方差的33%以上（p<0.001），包括乳房密度，乳房的致密和非致密区域分别与产次（遗传相关性（ρG）=-0.47; p=0.013）和初潮年龄（ρG=-0.38; p=0.008）显著遗传相关。乳腺的非致密区，以及乳腺密度（以致密区与总面积的比值表示），也与大多数肥胖指标存在遗传相关性，但方向相反（ρG≥0.75;非致密区p<10−7）。我们的结论是，影响乳腺密度的遗传成分并不独立于影响其他乳腺癌风险因素的遗传成分。这种共同的遗传结构应该在未来的乳腺密度遗传研究中加以考虑。
Previous twin and family studies indicate that the familial aggregation of breast density is due (in part) to genetic factors. Whether these genetic influences are shared with other breast cancer risk factors, however, is not known. Using standard film-screen mammography, we screened 550 women, including 611 pairs of sisters, from the Old Order Amish population of Lancaster County, Pennsylvania. We digitized mammograms and quantified the dense and non-dense areas of the breast using a computer-assisted method. Information about other breast cancer risk factors was collected via questionnaires and a physical exam. Using pedigree-based variance component methods, we estimated the genetic contributions to several breast cancer risk factors, including breast density, and evaluated the evidence for shared genetic influences between them. After adjusting for covariates, genetic effects accounted for more than 33% of the total variance of each risk factor (p<0.001), including breast density, and the dense and non-dense areas of the breast were significantly genetically correlated with parity (genetic correlation (ρG)=−0.47; p=0.013) and age at menarche (ρG=−0.38; p=0.008), respectively. The non-dense area of the breast, and in turn, breast density, expressed as a ratio of dense area to total area, were also genetically correlated with most measures of adiposity but in opposite directions (ρG≥0.75; p<10−7 for non-dense area). We conclude that the genetic components that influence breast density are not independent of the genetic components that influence other breast cancer risk factors. This shared genetic architecture should be considered in future genetic studies of breast density.