van Harten-Gerritsen A Suzanne, Balvers Michiel G J, Witkamp Renger F, Kampman Ellen, van Duijnhoven Fränzel J B
Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.
Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands. Clinical Chemistry and Haematology Laboratory, Gelderse Vallei Hospital, Ede, the Netherlands.
Cancer Epidemiol Biomarkers Prev. 2015 Dec;24(12):1820-8. doi: 10.1158/1055-9965.EPI-15-0601. Epub 2015 Sep 22.
Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a valuable next step. This review starts with an overview of inflammatory processes suggested to be involved in colorectal cancer progression and regulated by vitamin D. Next, we provide recommendations on how to study inflammatory markers in future epidemiologic studies on vitamin D and colorectal cancer survival. Mechanistic studies have shown that calcitriol-active form of vitamin D-influences inflammatory processes involved in cancer progression, including the enzyme cyclooxygenase 2, the NF-κB pathway, and the expression of the cytokines TNFα, IL1β, IL6, IL8, IL17, and TGFβ1. Based on this and taking into account methodologic issues, we recommend to include analysis of specific soluble peptides and proteins, such as cytokines, in future epidemiologic studies on this issue. Vitamin D and the markers should preferably be measured at multiple time points during disease progression or recovery and analyzed using mediation analysis. Including these markers in epidemiologic studies may help answer whether inflammation mediates a causal relationship between vitamin D and colorectal cancer survival.
结直肠癌的生存率与维生素D水平呈正相关。然而，这种关联是否具有因果关系仍不明确。炎症过程可能将维生素D与结直肠癌的生存率联系起来，因此，将炎症标志物作为潜在的介导因素进行研究可能是有价值的下一步。本综述首先概述了被认为参与结直肠癌进展并受维生素D调节的炎症过程。接下来，我们就如何在未来关于维生素D与结直肠癌生存率的流行病学研究中研究炎症标志物提供建议。机制研究表明，维生素D的活性形式骨化三醇会影响癌症进展中涉及的炎症过程，包括环氧合酶2、NF-κB途径以及细胞因子TNFα、IL1β、IL6、IL8、IL17和TGFβ1的表达。基于此并考虑到方法学问题，我们建议在未来关于这个问题的流行病学研究中纳入对特定可溶性肽和蛋白质（如细胞因子）的分析。维生素D和这些标志物最好在疾病进展或恢复期间的多个时间点进行测量，并使用中介分析进行分析。在流行病学研究中纳入这些标志物可能有助于回答炎症是否介导了维生素D与结直肠癌生存率之间的因果关系。
