Tagliabue Elena, Raimondi Sara, Gandini Sara
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
Adv Food Nutr Res. 2015;75:1-52. doi: 10.1016/bs.afnr.2015.06.003. Epub 2015 Aug 5.
Antiproliferative effects of 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, are well established in various cell types by influencing cell differentiation and decreasing cell proliferation, growth, invasion, angiogenesis, and metastasis. Several meta-analyses showed that low serum levels of 25(OH)D was associated with colorectal cancer and overall mortality, while the association with cancer mortality was less consistent. VDR is a crucial mediator for the cellular effects of vitamin D and conflicting data have been reported for most malignancies. Beyond VDR, the biological effects of vitamin D are mediated by the vitamin D-binding protein. The GC (group-specific component) gene, encoding DBP, is highly polymorphic and several polymorphisms were investigated in association with cancer development with controversial results. Vitamin D supplementation was found to be associated with a reduced risk of overall mortality, reviewing all published trials on healthy subjects, whereas the evidence of an effect on cancer risk and mortality is less clear. Furthermore, long-term health effects of high doses of vitamin D, extended duration of supplementation, and the association with different baseline vitamin D levels remain to be investigated. In summary, epidemiological and preclinical studies support the development of vitamin D as preventative and therapeutic anticancer agents, with significant associations especially found for low vitamin D status with overall mortality and cancer outcome, more than cancer incidence. However, a definitive conclusion cannot be drawn and only large randomized clinical trials, both in healthy subjects and in cancer patients, will allow to draw definitive conclusions on the effect of vitamin D supplementation on cancer risk, prognosis, and mortality.
1,25 - 二羟基维生素D（维生素D的生物活性形式）的抗增殖作用已在多种细胞类型中得到充分证实，它通过影响细胞分化以及降低细胞增殖、生长、侵袭、血管生成和转移来发挥作用。多项荟萃分析表明，血清25(OH)D水平低与结直肠癌及全因死亡率相关，而与癌症死亡率的关联则不太一致。维生素D受体（VDR）是维生素D细胞效应的关键介质，对于大多数恶性肿瘤，都有相互矛盾的数据报道。除了VDR，维生素D的生物学效应还由维生素D结合蛋白介导。编码DBP的GC（群体特异性成分）基因具有高度多态性，多项多态性与癌症发生的关联研究结果存在争议。对所有已发表的关于健康受试者的试验进行综述发现，补充维生素D与降低全因死亡风险相关，而对癌症风险和死亡率影响的证据则不太明确。此外，高剂量维生素D的长期健康影响、延长补充时间以及与不同基线维生素D水平的关联仍有待研究。总之，流行病学和临床前研究支持将维生素D开发为预防和治疗癌症的药物，尤其是低维生素D状态与全因死亡率和癌症结局之间存在显著关联，这种关联在癌症发病率方面更为明显。然而，目前尚不能得出明确结论，只有针对健康受试者和癌症患者的大型随机临床试验才能就补充维生素D对癌症风险、预后和死亡率的影响得出明确结论。
