Evaluation of Expression Levels of Vitamin D Receptor and Metabolizing Enzymes (CYP24A1 and CYP27B1) in a cohort of Egyptian Females with Breast Cancer

Abstract

Background:Active vitamin D has recognized antitumor properties. Its tissue concentration is mainly regulated by 24-hydroxylase (CYP24A1) and 1α-hydroxylase (CYP27B1). This study investigated the expression of CYP24A1, CYP27B1, and the vitamin D receptor (VDR) mRNA in breast cancer tissues compared with adjacent normal tissues of Egyptian females, and examined their associations with clinicopathological features and molecular subtypes.Methods:A total of 44 operable primary breast cancer patients were included. Biopsies from malignant and adjacent normal breast tissues were analyzed for relative mRNA expression of CYP24A1, CYP27B1, and VDR using quantitative methods. Correlations with clinical, pathological, and molecular characteristics were assessed.Results:No overall significant differences in CYP24A1, CYP27B1, or VDR mRNA expression were observed across clinicopathological variables. A significant positive correlation was found between VDR and CYP27B1 expression. In patients >50 years, VDR correlated positively with CYP27B1, CYP27B1 correlated positively with molecular subtype and negatively with progesterone receptor status, while CYP24A1 correlated negatively with tumor grade. In patients ≤50 years, VDR correlated positively with estrogen and progesterone receptors and with CYP27B1, but negatively with tumor stage.Conclusion:Vitamin D metabolism–related genes may play an important role in breast cancer biology. CYP24A1 and CYP27B1 mRNA expression could be considered potential markers for disease progression. Dysregulated vitamin D catabolism and anabolism in malignant breast tissue may attenuate its antitumor effects.Keywords: Breast cancer; CYP24A1; CYP27B1; VDR; molecular subtypes