Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?

Abstract 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 defin...

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Autores principales: Favour A. Akinjiyan, Yunan Han, Jingqin Luo, Adetunji T. Toriola
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Publicado: Springer 2021
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spelling oai:doaj.org-article:c2fd4dc4065b423280d5e5486777ba512021-11-08T11:19:23ZDoes circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?10.1007/s12672-021-00438-12730-6011https://doaj.org/article/c2fd4dc4065b423280d5e5486777ba512021-11-01T00:00:00Zhttps://doi.org/10.1007/s12672-021-00438-1https://doaj.org/toc/2730-6011Abstract 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.Favour A. AkinjiyanYunan HanJingqin LuoAdetunji T. ToriolaSpringerarticleProgesteroneGeneticsMammographic breast densitySNPsBreastPremenopausalNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENDiscover Oncology, Vol 12, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Progesterone
Genetics
Mammographic breast density
SNPs
Breast
Premenopausal
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Progesterone
Genetics
Mammographic breast density
SNPs
Breast
Premenopausal
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Favour A. Akinjiyan
Yunan Han
Jingqin Luo
Adetunji T. Toriola
Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?
description Abstract 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.
format article
author Favour A. Akinjiyan
Yunan Han
Jingqin Luo
Adetunji T. Toriola
author_facet Favour A. Akinjiyan
Yunan Han
Jingqin Luo
Adetunji T. Toriola
author_sort Favour A. Akinjiyan
title Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?
title_short Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?
title_full Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?
title_fullStr Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?
title_full_unstemmed Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?
title_sort does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (pgr)-related genes with mammographic breast density in premenopausal women?
publisher Springer
publishDate 2021
url https://doaj.org/article/c2fd4dc4065b423280d5e5486777ba51
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AT jingqinluo doescirculatingprogesteronemediatetheassociationsofsinglenucleotidepolymorphismsinprogesteronereceptorpgrrelatedgeneswithmammographicbreastdensityinpremenopausalwomen
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