Vitamin D receptor polymorphisms and their role in invasive breast cancer progression

Vitamin D plays a critical role not only in maintaining bone health and regulating calcium levels, but is also involved in several extra-skeletal functions, including cell physiology, proliferation, differentiation, anti-cancer effects, modulation of immune responses, and inflammation control. Its biological effects are mediated by the nuclear vitamin D receptor (VDR), a member of the steroid hormone receptor family. Genetic variations in this VDR gene, such as the FokI (rs2228570) and TaqI (rs731236) single nucleotide polymorphisms (SNPs), may alter VDR expression levels, impair protein function, and potentially increase the risk of breast cancer. However, the relationship between these polymorphisms and breast cancer remains controversial. This study aims to assess the association between the FokI and TaqI polymorphisms of the VDR gene and breast cancer susceptibility in Moroccan women. For this study, breast cancer tissues and control samples were collected, and genomic DNA was extracted. Genotyping of FokI and TaqI SNPs was performed using TaqMan Real-Time Polymerase Chain Reaction (RT-PCR). Our findings revealed a significant difference in the distribution of FokI genotypes between breast cancer patients and controls (p = 0.031). The FokI polymorphism was significantly associated with histoprognostic grade (p < 0.001), tumor stage (p = 0.011), and progesterone receptor (PR) status (p = 0.004), while the TaqI polymorphism showed a significant association with estrogen receptor (ER) status (p = 0.016). These results suggest that the FokI polymorphism of the VDR gene may influence breast cancer susceptibility. Identifying these genetic variations could provide valuable insights into breast cancer pathogenesis and open avenues for personalized treatment strategies, including the use of VDR agonists as targeted therapies against breast cancer.