文章：

维生素D在降低癌症风险和进展中的作用

The role of vitamin D in reducing cancer risk and progression

原文发布日期：2014-04-04

DOI: 10.1038/nrc3691

类型: Review Article

开放获取: 否

要点：

1. Vitamin D₃ is the precursor to the potent steroid hormone calcitriol (1,25 dihydroxyvitamin D₃ (1,25(OH)₂D₃)) that regulates the expression of many genes in most tissues of the body.
2. Dietary vitamin D₃ is converted into 25 hydroxyvitamin D₃ (25(OH)D₃) in the liver; this is the circulating form of vitamin D, which is subsequently hydroxylated to form calcitriol by the cytochrome P450 enzyme CYP27B1 in the kidneys. Calcitriol is also synthesized locally by CYP27B1 present in most extrarenal tissues, including many cancer cells, where it acts in a paracrine manner. Levels of calcitriol are additionally regulated by the cytochrome P450 enzyme CYP24A1, which begins the inactivation of calcitriol through 24-hydroxylation.
3. Calcitriol regulates multiple signalling pathways involved in proliferation, apoptosis, differentiation, inflammation, invasion, angiogenesis and metastasis, and it therefore has the potential to affect cancer development and growth. Recent findings indicate that calcitriol also regulates microRNA expression and may affect cancer stem cell biology.
4. Multiple cell culture and animal models of cancer support a role for dietary vitamin D₃ and calcitriol in retarding cancer development and progression; however, data from human clinical trials are thus far inconsistent.
5. Epidemiological studies suggest that vitamin D deficiency is associated with increased incidence of cancer and worse outcomes, although many studies do not demonstrate these associations.
6. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D₃ synthesis and degradation pathways have been implicated in affecting the risk of cancer development.
7. Given the interest in using vitamin D₃ to reduce cancer risk, further research is needed, particularly randomized controlled trials (RCTs), to demonstrate in humans whether individuals with low levels of circulating 25(OH)D are at increased risk of developing cancer and whether calcitriol or vitamin D supplements can reduce cancer risk and progression and improve outcomes.

要点翻译：

1. 维生素D3是强效类固醇激素骨化三醇（1,25-二羟基维生素D3）的前体，这种激素可调节人体大多数组织中多种基因的表达。
2. 膳食中的维生素D3在肝脏中转化为25-羟基维生素D3，这是维生素D的循环形式，随后通过肾脏中细胞色素P450酶CYP27B1羟化形成骨化三醇。骨化三醇也可由存在于大多数肾外组织（包括多种癌细胞）中的CYP27B1局部合成，并以旁分泌方式发挥作用。骨化三醇的水平还受到细胞色素P450酶CYP24A1的调控，该酶通过24-羟化反应启动骨化三醇的失活过程。
3. 骨化三醇调控涉及增殖、凋亡、分化、炎症、侵袭、血管生成和转移的多种信号通路，因此可能影响癌症的发生与发展。最新研究表明，骨化三醇还能调控微小RNA的表达，并可能影响癌症干细胞生物学。
4. 多项细胞培养和动物癌症模型研究支持膳食维生素D3与骨化三醇具有延缓癌症发生发展的作用，但截至目前，人体临床试验数据仍不一致。
5. 流行病学研究表明维生素D缺乏与癌症发病率上升及预后不良相关，但许多研究并未证实这些关联。
6. 维生素D受体（VDR）及维生素D3合成与降解通路中的单核苷酸多态性（SNPs）已被证实与癌症发生风险相关。
7. 鉴于维生素D3在降低癌症风险方面的应用潜力，需要开展进一步研究（特别是随机对照试验），以在人体中证实循环25(OH)D水平偏低者是否具有更高的患癌风险，以及骨化三醇或维生素D补充剂能否降低癌症风险和进展并改善预后。

英文摘要：

Vitamin D is not really a vitamin but the precursor to the potent steroid hormone calcitriol, which has widespread actions throughout the body. Calcitriol regulates numerous cellular pathways that could have a role in determining cancer risk and prognosis. Although epidemiological and early clinical trials are inconsistent, and randomized control trials in humans do not yet exist to conclusively support a beneficial role for vitamin D, accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.

摘要翻译： 

维生素D并非真正的维生素，而是强效类固醇激素骨化三醇的前体，其在全身具有广泛作用。骨化三醇可调节众多可能参与决定癌症风险和预后的细胞通路。尽管流行病学和早期临床试验结果不一致，且目前尚缺乏人类随机对照试验明确证实维生素D的益处，但越来越多的临床前研究及部分临床研究结果强烈提示，维生素D缺乏会增加患癌风险，而避免缺乏并补充维生素D可能是一种经济且安全的方法，有助于降低癌症发病率、改善癌症预后和结局。

原文链接：

The role of vitamin D in reducing cancer risk and progression