INTERNATIONAL CONGRESS OF
PharmacoGenetics
Vitamin D Pharmacogenomics in Cancer: Genetic and Metabolic Insights for Personalized Therapy
-
zahra seifi ,1,*
1. Student research committee, Kermanshah university of Medical sciences
- Introduction: Vitamin D, a hormone similar to steroids, can be produced within the body and is also found in foods such as mushrooms, fish, eggs, liver, and foods that have been fortified. While it has long been associated with maintaining calcium balance and supporting bone health, emerging research has revealed its wider physiological effects, particularly in the realm of cancer prevention and treatment. In addition to its role in mineral regulation, vitamin D also affects gene expression, impacts cell cycle regulators, encourages apoptosis and autophagy, regulates the formation of new blood vessels, and demonstrates anti-inflammatory and antioxidant properties. Its diverse functions make it a compound of significance in cancer research, especially regarding pharmacogenomics, which explores how genetic differences influence drug metabolism and responses.
- Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science, focusing on studies published in the last two decades. Keywords included "vitamin D," "CYP3A4," "pharmacogenomics," "cancer," "miRNA," and "metabolism." Both in vitro and clinical studies were included to assess the influence of vitamin D levels, genetic polymorphisms in metabolizing enzymes, and their impact on cancer risk and chemotherapy efficacy. Special attention was given to studies exploring CYP3A4-mediated metabolism, interactions with chemotherapeutic agents such as irinotecan, and regulatory effects on molecular pathways relevant to tumorigenesis.
- Results: Vitamin D metabolism is primarily facilitated by the microsomal enzyme CYP3A4, which is abundantly expressed in the liver. CYP3A4 is responsible for catalyzing the 24- and 25-hydroxylation of both vitamin D2 and D3, as well as the tissue-specific conversion of these vitamins into inactive forms, such as 4β,25-OH-D3. Genetic polymorphisms affecting CYP3A4 can significantly influence enzyme activity, thereby impacting serum vitamin D levels and subsequent biological effects. Additionally, environmental factors—including medications, herbal supplements, and dietary flavonoids—can further modulate CYP3A4 activity. Functionally, 1,25(OH)2D3, the biologically active form of vitamin D, regulates cellular proliferation by upregulating the proteins p21 and p27. It also induces apoptosis and autophagy and modulates angiogenesis. Moreover, it serves to suppress inflammatory mediators such as IL-2, IL-12, TNF-α, and interferon-gamma, while regulating signaling pathways, including NF-κB, MAPK, and COX-2, which are known to play roles in cancer progression. In the realm of chemotherapy, vitamin D has demonstrated the capacity to enhance the efficacy of irinotecan through a CYP3A4-dependent mechanism, which involves the modulation and induction of miR-627, thereby augmenting anti-tumor activity. Furthermore, in vitro studies indicate that CYP3A4 is capable of metabolizing other active forms of vitamin D and 20(OH)D3, potentially influencing tumor cell proliferation. Pharmacogenomic investigations reveal that polymorphisms within CYP3A4 and associated enzymes may serve as predictors for patient-specific responses to vitamin D supplementation and chemotherapeutic agents. This individualized response underscores the potential for integrating vitamin D pharmacogenomics into precision oncology, thereby optimizing therapeutic outcomes while minimizing adverse effects. The interaction between vitamin D metabolism and genetic variability highlights its significance in personalized cancer therapy. CYP3A4-mediated vitamin D metabolism not only impacts systemic vitamin D levels but also influences the effectiveness of chemotherapeutic agents. By considering individual genetic profiles, clinicians may be better equipped to tailor vitamin D supplementation and combination therapies to enhance therapeutic efficacy. Furthermore, an understanding of the underlying molecular mechanisms—such as the regulation of apoptosis, angiogenesis, inflammation, and miRNA-mediated drug metabolism—yields valuable insights into the anti-cancer potential of vitamin D. Future research should prioritize large-scale clinical studies that integrate pharmacogenomic profiling with vitamin D status to establish predictive biomarkers for cancer risk and therapeutic responsiveness. In addition, investigations into gene-environment interactions, specifically those involving dietary factors and natural compounds that affect CYP3A4, will contribute to the refinement of personalized treatment strategies.
- Conclusion: Vitamin D functions as a versatile regulator of cellular balance and cancer biology. Its metabolism is closely associated with CYP3A4 activity and genetic variations, highlighting the significance of pharmacogenomic factors in clinical practices. Incorporating vitamin D pharmacogenomics into cancer treatment presents encouraging opportunities for personalized medicine, enhancing patient outcomes and potentially aiding in the creation of new therapeutic approaches.
- Keywords: Vitamin D, CYP3A4, Pharmacogenomics, Cancer
