Abstract Vitamin D3 (1,25-dihydroxyvitamin D3 (1,25(OH)2D3)), has been hypothesized to be associated with breast cancer initiation and progression through several different mechanisms. In addition to playing a key role calcium and phosphate homeostasis, it has been shown to be involved in various processes associated with carcinogenesis, including immune modulation, proliferation, and cellular differentiation. Population-based studies have consistently shown circulating levels of vitamin D3 are lower among African American populations compared to other racial and ethnic groups in the United States. Epidemiologic evidence is mixed as to whether circulating vitamin D3 levels are associated with risk of developing breast cancer, with a recent meta-analysis reporting null results. Fewer reports examine the association between tissue-based markers of vitamin D3 metabolism and breast cancer risk. Here, we seek to determine whether the target of vitamin D3, the Vitamin D Receptor (VDR), and vitamin D3 synthesizing and degrading enzymes (CYP24A1, CYP27B1, respectively) are present in normal breast tissue, and if so, whether presence in the tissue is associated with risk of subsequent breast cancer. We utilized tissue specimens from the Susan G. Komen Tissue Bank at Indiana University to determine the expression of VDR, CYP24a1 and CYP27b1 in tissue from healthy, cancer-free donors. We selected n=14 women who developed a subsequent breast cancer, age, self-reported race and ethnicity-matched to n=28 women who did not develop cancer. Healthy breast tissue from n=4 men were also included, although results are preliminary and will only be described. Immunohistochemistry (IHC) was performed for VDR (Cell Signaling), CYP24A1 (Invitrogen) and CYP27B1 (Santa Cruz Biotechnology) on the formalin-fixed, paraffin-embedded tissue. Slides will be scored by a breast pathologist to determine the amount and intensity of the staining. Descriptive statistics will be used to summarize donor characteristics and IHC markers, including results stratified by self-reported race. Correlations between IHC markers will also be assessed. Logistic regression models will be performed to determine if an association exists between VDR, CYP24A1, CYP27B1 and development of breast cancer. Understanding the protein expression of normal breast tissue in those who do and do not develop breast cancer may identify pathways amenable to prevention strategies. Citation Format: Anastasia Ebersole, Rana German, Michele L. Cote. Markers of vitamin D3 activity in normal breast tissue and subsequent breast cancer: A pilot study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B067.
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