Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
Breast Cancer Res. 2010;12(2):R19. doi: 10.1186/bcr2488. Epub 2010 Mar 9.
Several studies have examined the effect of genetic variants in genes involved in the estrogen metabolic pathway on mammographic density, but the number of loci studied and the sample sizes evaluated have been small and pathways have not been evaluated comprehensively. In this study, we evaluate the association between mammographic density and genetic variants of the estrogen metabolic pathway.
A total of 239 SNPs in 34 estrogen metabolic genes were studied in 1,731 Swedish women who participated in a breast cancer case-control study, of which 891 were cases and 840 were controls. Film mammograms of the medio-lateral oblique view were digitalized and the software Cumulus was used for computer-assisted semi-automated thresholding of mammographic density. Generalized linear models controlling for possible confounders were used to evaluate the effects of SNPs on mammographic density. Results found to be nominally significant were examined in two independent populations. The admixture maximum likelihood-based global test was performed to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three subpathways for androgen synthesis, androgen-to-estrogen conversion and estrogen removal.
Genetic variants of genes involved in estrogen metabolism exhibited no appreciable effect on mammographic density. None of the nominally significant findings were validated. In addition, global analyses on the overall estrogen metabolic pathway and its subpathways did not yield statistically significant results.
Overall, there is no conclusive evidence that genetic variants in genes involved in the estrogen metabolic pathway are associated with mammographic density in postmenopausal women.
已有多项研究探讨了参与雌激素代谢途径的基因中的遗传变异对乳腺密度的影响，但所研究的基因座数量和评估的样本量都较小，且未全面评估途径。在这项研究中，我们评估了雌激素代谢途径的遗传变异与乳腺密度之间的关系。
我们在参加乳腺癌病例对照研究的 1731 名瑞典女性中研究了 34 个雌激素代谢基因中的 239 个 SNP，其中 891 例为病例，840 例为对照。对侧斜位的胶片乳房 X 光片进行数字化，使用 Cumulus 软件进行计算机辅助半自动阈值化乳腺密度。使用控制可能混杂因素的广义线性模型评估 SNP 对乳腺密度的影响。对具有名义显著性的结果在两个独立的人群中进行了检查。采用混合最大似然全局检验评估整个代谢途径以及雄激素合成、雄激素向雌激素转化和雌激素去除三个亚途径中多个 SNP 的累积效应。
参与雌激素代谢的基因中的遗传变异对乳腺密度没有明显影响。没有一个具有名义显著性的发现得到验证。此外，对整个雌激素代谢途径及其亚途径的全局分析没有产生统计学上显著的结果。
总体而言，没有确凿的证据表明参与雌激素代谢途径的基因中的遗传变异与绝经后女性的乳腺密度有关。
