Zheng Sijie, Zhu Lizhu, Wang Yufei, Hua Yixin, Ying Jie, Chen Jianxiang
College of Pharmacy and Department of Hepatology, Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Department of Gastroenterology, Affiliated Nanjing Jiangbei Hospital of Xinglin College, Nantong University, Nanjing, China.
Front Genet. 2025 Jun 24;16:1598525. doi: 10.3389/fgene.2025.1598525. eCollection 2025.
Vitamin D is an essential vitamin for normal human metabolism and plays pivotal roles in various biological processes, such as maintaining calcium and phosphorus balance, regulating immune responses, and promoting cell differentiation while inhibiting proliferation. Vitamin D is obtained through sunlight exposure and diet, and is metabolized into its active form via hydroxylation in liver and kidney. Vitamin D deficiency is linked to various diseases, including skeletal disorders, diabetes, and cardiovascular diseases. Recent epidemiology and oncology research have demonstrated that serum vitamin D level, as well as genetic polymorphisms and expression dysregulation of genes related with vitamin D metabolism, have significantly influences on the incidence and prognosis of various types of cancer, including breast cancer, prostate cancer, liver cancer, gastrointestinal malignancy, and hematologic malignancies. The mechanisms linking vitamin D metabolism dysregulation to malignancy are multifactorial, such as the alteration in cell metabolism, proliferation, differentiation, and tumor microenvironment. These findings suggest potential therapeutic benefits of targeting the vitamin D signaling pathway for the diagnosis and treatment of cancer. However, there is still a lack of clinical applications regarding the knowledge of vitamin D metabolic pathway, and future research is urgently needed to illustrate the underlying mechanisms for the rationale design of clinical trials. Therefore, this review summarizes the metabolic pathways of vitamin D and its association with cancer, highlighting the importance of genetic polymorphisms and expression dysregulation of genes involved in vitamin D metabolism in cancer susceptibility and prognosis.
维生素D是人体正常代谢所必需的维生素，在维持钙磷平衡、调节免疫反应、促进细胞分化并抑制增殖等多种生物学过程中发挥关键作用。维生素D可通过阳光照射和饮食获取，并在肝脏和肾脏中经羟基化代谢为其活性形式。维生素D缺乏与多种疾病相关，包括骨骼疾病、糖尿病和心血管疾病。近期的流行病学和肿瘤学研究表明，血清维生素D水平以及与维生素D代谢相关的基因多态性和基因表达失调，对包括乳腺癌、前列腺癌、肝癌、胃肠道恶性肿瘤和血液系统恶性肿瘤在内的各类癌症的发病率和预后均有显著影响。维生素D代谢失调与恶性肿瘤之间的关联机制是多因素的，如细胞代谢、增殖、分化及肿瘤微环境的改变。这些发现提示，针对维生素D信号通路进行癌症诊断和治疗可能具有潜在的治疗益处。然而，关于维生素D代谢途径的知识仍缺乏临床应用，迫切需要未来的研究阐明其潜在机制，以便为临床试验的合理设计提供依据。因此，本综述总结了维生素D的代谢途径及其与癌症的关联，强调了参与维生素D代谢的基因多态性和基因表达失调在癌症易感性和预后中的重要性。
