Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women
Abstract Background Hormones impact breast tissue proliferation. Studies investigating the associations of circulating hormone levels with mammographic breast density have reported conflicting results. Due to the limited number of studies, we investigated the associations of hormone gene expression...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-022-01522-2 |
| _version_ | 1817990513652924416 |
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| author | Rachel Mintz Mei Wang Shuai Xu Graham A. Colditz Chris Markovic Adetunji T. Toriola |
| author_facet | Rachel Mintz Mei Wang Shuai Xu Graham A. Colditz Chris Markovic Adetunji T. Toriola |
| author_sort | Rachel Mintz |
| collection | DOAJ |
| description | Abstract Background Hormones impact breast tissue proliferation. Studies investigating the associations of circulating hormone levels with mammographic breast density have reported conflicting results. Due to the limited number of studies, we investigated the associations of hormone gene expression as well as their downstream mediators within the plasma with mammographic breast density in postmenopausal women. Methods We recruited postmenopausal women at their annual screening mammogram at Washington University School of Medicine, St. Louis. We used the NanoString nCounter platform to quantify gene expression of hormones (prolactin, progesterone receptor (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1 and STAT5), and receptor activator of nuclear factor-kB (RANK) pathway markers (RANK, RANKL, osteoprotegerin, TNFRSF18, and TNFRSF13B) in plasma. We used Volpara to measure volumetric percent density, dense volume, and non-dense volume. Linear regression models, adjusted for confounders, were used to evaluate associations between gene expression (linear fold change) and mammographic breast density. Results One unit increase in ESR1, RANK, and TNFRSF18 gene expression was associated with 8% (95% CI 0–15%, p value = 0.05), 10% (95% CI 0–20%, p value = 0.04) and % (95% CI 0–9%, p value = 0.04) higher volumetric percent density, respectively. There were no associations between gene expression of other markers and volumetric percent density. One unit increase in osteoprotegerin and PGR gene expression was associated with 12% (95% CI 4–19%, p value = 0.003) and 7% (95% CI 0–13%, p value = 0.04) lower non-dense volume, respectively. Conclusion These findings provide new insight on the associations of plasma hormonal and RANK pathway gene expression with mammographic breast density in postmenopausal women and require confirmation in other studies. |
| first_indexed | 2024-04-14T01:00:04Z |
| format | Article |
| id | doaj.art-10b4c79c0dab481882d444deed9d760a |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-04-14T01:00:04Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-10b4c79c0dab481882d444deed9d760a2022-12-22T02:21:26ZengBMCBreast Cancer Research1465-542X2022-04-0124111110.1186/s13058-022-01522-2Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal womenRachel Mintz0Mei Wang1Shuai Xu2Graham A. Colditz3Chris Markovic4Adetunji T. Toriola5Biomedical Engineering Department, Washington UniversityDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineMcDonnell Genome Institute at Washington UniversityDivision of Public Health Sciences, Department of Surgery, Washington University School of MedicineAbstract Background Hormones impact breast tissue proliferation. Studies investigating the associations of circulating hormone levels with mammographic breast density have reported conflicting results. Due to the limited number of studies, we investigated the associations of hormone gene expression as well as their downstream mediators within the plasma with mammographic breast density in postmenopausal women. Methods We recruited postmenopausal women at their annual screening mammogram at Washington University School of Medicine, St. Louis. We used the NanoString nCounter platform to quantify gene expression of hormones (prolactin, progesterone receptor (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1 and STAT5), and receptor activator of nuclear factor-kB (RANK) pathway markers (RANK, RANKL, osteoprotegerin, TNFRSF18, and TNFRSF13B) in plasma. We used Volpara to measure volumetric percent density, dense volume, and non-dense volume. Linear regression models, adjusted for confounders, were used to evaluate associations between gene expression (linear fold change) and mammographic breast density. Results One unit increase in ESR1, RANK, and TNFRSF18 gene expression was associated with 8% (95% CI 0–15%, p value = 0.05), 10% (95% CI 0–20%, p value = 0.04) and % (95% CI 0–9%, p value = 0.04) higher volumetric percent density, respectively. There were no associations between gene expression of other markers and volumetric percent density. One unit increase in osteoprotegerin and PGR gene expression was associated with 12% (95% CI 4–19%, p value = 0.003) and 7% (95% CI 0–13%, p value = 0.04) lower non-dense volume, respectively. Conclusion These findings provide new insight on the associations of plasma hormonal and RANK pathway gene expression with mammographic breast density in postmenopausal women and require confirmation in other studies.https://doi.org/10.1186/s13058-022-01522-2Mammographic breast densityHormonesRANKRANKLGene expression |
| spellingShingle | Rachel Mintz Mei Wang Shuai Xu Graham A. Colditz Chris Markovic Adetunji T. Toriola Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women Breast Cancer Research Mammographic breast density Hormones RANK RANKL Gene expression |
| title | Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women |
| title_full | Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women |
| title_fullStr | Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women |
| title_full_unstemmed | Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women |
| title_short | Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women |
| title_sort | hormone and receptor activator of nf κb rank pathway gene expression in plasma and mammographic breast density in postmenopausal women |
| topic | Mammographic breast density Hormones RANK RANKL Gene expression |
| url | https://doi.org/10.1186/s13058-022-01522-2 |
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