Genetic Models for the Familial Aggregation of Mammographic Breast Density
Genetic Models for the Familial Aggregation of Mammographic Breast Density
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DOI：
10.1158/1055-9965.epi-08-0568
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发表时间：
2009-04-01
影响因子：
3.8
通讯作者：
Easton, Doug
中科院分区：
文献类型：
--
作者：
Kataoka, Masako;Antoniou, Antonis;Easton, Doug
背景：乳腺钼靶摄影乳腺密度（MBD）有很强的遗传成分。研究乳腺X线摄影密度的遗传模型可以进一步了解影响乳腺癌风险的遗传因素。目的：评估MBD的家族聚集性，并研究易感性的遗传模型。使用了来自305个家庭的746名妇女的数据，这些妇女参加了乳房筛查研究中的姐妹篇。将检索的乳房X线照片数字化，并使用Cumulus软件确定乳房X线照片密度百分比。采用线性回归分析确定影响乳腺摄影密度的因素，并建立多元回归模型。使用这些模型的残差计算亲属对之间的家族相关性。结果：经协变量校正后，姐妹间残差的组内相关系数为0.26（95%可信区间为0.16-0.36），同卵双生子为0.67（0.27-1.00）。最简约的模型是孟德尔单主基因模型，其中等位基因的群体频率为0.39（95%置信区间，0.33-0.46）影响乳腺摄影密度的加性方式。该模型解释了66%的残差方差。结论：这些结果证实了MBD有很强的遗传基础，并建议主基因可能解释一些家庭聚集性。这些结果可能对寻找控制乳腺摄影密度的基因有意义。（Cancer Epidemiol Biomarkers Prev 2009;18（4）：1277-84）
Background: Mammographic breast density (MBD) has a strong genetic component. Investigating the genetic models for mammographic density may provide further insights into the genetic factors affecting breast cancer risk.Purpose: To evaluate the familial aggregation of MBD and investigate the genetic models of susceptibility.Methods: WE! used data on 746 women from 305 families participating in the Sisters in Breast Screening study. Retrieved mammograms were digitized, and percent mammographic density was determined using the Cumulus software. Linear regression analysis was done to identify the factors that are associated with mammographic density and a multivariate regression model was constructed. Familial correlations between relative pairs were calculated using the residuals from these models. Genetic models of susceptibility were investigated using segregation analysis.Results: After adjusting for covariates, the intraclass correlation coefficient among the residuals was 0.26 (95% confidence interval, 0.16-0.36) in sister-sister pairs and 0.67 (0.27-1.00) among the monozygotic twin pairs. The most parsimonious model was a Mendelian single major gene model in which an allele with population frequency 0.39 (95% confidence interval, 0.33-0.46) influenced mammographic density in an additive fashion. This model explained 66% of the residual variance.Conclusion: These results confirm that MBD has a strong heritable basis, and suggest that major genes may explain some of the familial aggregation. These results may have implications for the search of genes that control mammographic density. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1277-84)