Akinjiyan Favour A, Han Yunan, Luo Jingqin, Toriola Adetunji T
Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110 USA.
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Campus Box 8100, 660 South Euclid Ave, St. Louis, MO 63110 USA.
Discov Oncol. 2021;12(1):47. doi: 10.1007/s12672-021-00438-1. Epub 2021 Nov 3.
Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through circulating progesterone are not clearly defined. We, therefore, investigated these associations in 364 premenopausal women with a median age of 44 years. We sequenced 179 progesterone receptor (PGR)-related single nucleotide polymorphisms (SNPs). We measured volumetric percent density (VPD) and non-dense volume (NDV) using Volpara. Linear regression models were fit on circulating progesterone or VPD/NDV separately. We performed mediation analysis to evaluate whether the effect of a SNP on VPD/NDV is mediated through circulating progesterone. All analyses were adjusted for confounders, phase of menstrual cycle and the Benjamini-Hochberg false discovery (FDR) adjusted p-value was applied to correct for multiple testing. In multivariable analyses, only PGR rs657516 had a direct effect on VPD (averaged direct effect estimate = - 0.20, 95%CI = - 0.38 ~ - 0.04, p-value = 0.02) but this was not statistically significant after FDR correction and the effect was not mediated by circulating progesterone (mediation effect averaged across the two genotypes = 0.01, 95%CI = - 0.02 ~ 0.03, p-value = 0.70). Five SNPs (PGR rs11571241, rs11571239, rs1824128, rs11571150, PGRMC1 rs41294894) were associated with circulating progesterone but these were not statistically significant after FDR correction. SNPs in PGR-related genes were not associated with VPD, NDV and circulating progesterone did not mediate the associations, suggesting that the effects, if any, of these SNPs on MD are independent of circulating progesterone.
The online version contains supplementary material available at 10.1007/s12672-021-00438-1.
孕酮是乳腺中的一种增殖激素，但绝经前女性中孕酮调节途径的基因变异与乳腺X线密度（MD）之间的关联，以及这些关联是否通过循环孕酮介导尚不清楚。因此，我们在364名中位年龄为44岁的绝经前女性中研究了这些关联。我们对179个孕酮受体（PGR）相关的单核苷酸多态性（SNP）进行了测序。我们使用Volpara测量了体积百分比密度（VPD）和非致密体积（NDV）。分别对循环孕酮或VPD/NDV拟合线性回归模型。我们进行了中介分析，以评估SNP对VPD/NDV的影响是否通过循环孕酮介导。所有分析均对混杂因素、月经周期阶段进行了校正，并应用Benjamini-Hochberg错误发现率（FDR）校正后的p值来校正多重检验。在多变量分析中，只有PGR rs657516对VPD有直接影响（平均直接效应估计值=-0.20，95%置信区间=-0.38-0.04，p值=0.02），但在FDR校正后无统计学意义，且该效应未通过循环孕酮介导（两种基因型的平均中介效应=0.01，95%置信区间=-0.020.03，p值=0.70）。五个SNP（PGR rs11571241、rs11571239、rs1824128、rs11571150、PGRMC1 rs41294894）与循环孕酮相关，但在FDR校正后无统计学意义。PGR相关基因中的SNP与VPD、NDV无关，循环孕酮也未介导这些关联，这表明这些SNP对MD的影响（如果有的话）独立于循环孕酮。
在线版本包含可在10.1007/s12672-021-00438-1获取的补充材料。
