Vitamin D and Vitamin D Receptor FokI, ApaI, and BsmI Gene Polymorphisms and their Relation with the Risk of Breast Carcinoma: A Case-control Study

Abstract

Introduction: Breast cancer stands as the leading cause of mortality among women in developing nations. The potential role of Vitamin D in mitigating the incidence of breast cancer is thought to stem from its ability to impede cell proliferation by interacting with the Vitamin D Receptor (VDR). The VDR gene is responsible for encoding the VDR, which plays a pivotal role in mediating the effects of vitamin D. Aim: To analyse vitamin D levels and the association of VDR FokI, ApaI, and BsmI genotypic distribution frequency with the risk of breast cancer. Materials and Methods: The case-control study included 220 samples, including 110 breast cancer patients and 110 agematched control women aged 30-70 years. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) genotyping was performed using Deoxyribonucleic acid (DNA) extracted from blood, and the circulating levels of 25-hydroxyvitamin D by case/control were estimated by chemiluminescence immunoassay. Results: The 3’ VDR polymorphism BsmI sequence showed minimal association with breast cancer risk. The bb genotype had a significantly lower odds ratio of 0.056 (p-value<0.05). Conversely, the BB and Bb genotypes exhibited no statistically significant associations with odds ratios of 1.76 (95% CI: 0.36-8.54; p-value>0.05) and 1.30 (95% CI: 0.27- 6.25; p-value>0.05), respectively. Isolated analysis of the FokI variant revealed a significant association with increased breast cancer risk, with odds ratios of 5.49 (FF) and 6.00 (Ff), both demonstrating statistical significance (p-value<0.05), and a Chi-square value of 0.006. Additionally, the p-value for serum Vitamin D levels was found to be highly significant at p-value<0.001, indicating that the levels were significantly lower in individuals newly diagnosed with breast cancer compared to those in the healthy control group. Conclusion: The study found a significant link between breast cancer susceptibility and VDR (FokI) polymorphism FF and Ff genotypes, with minimal impact observed for (BsmI) polymorphism bb genotype. This implies that certain genetic variations, especially in the FokI polymorphism of the VDR gene, are associated with an elevated risk of breast cancer.