Division of Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.
Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
Br J Nutr. 2020 May 28;123(10):1187-1200. doi: 10.1017/S0007114520000422. Epub 2020 Feb 5.
B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
参与一碳代谢的 B 族维生素与炎症和血管生成相关的慢性疾病（如结直肠癌（CRC））的发展有关。然而，一碳代谢在 CRC 患者的炎症和血管生成中的作用尚不清楚。本研究的目的是在海德堡前瞻性 ColoCare 研究中，调查初诊 CRC 患者（n=238）中一碳代谢成分与炎症和血管生成生物标志物之间的关联。我们使用多变量线性回归模型，对术前血清样本中 12 种 B 族维生素和一碳代谢物与 10 种炎症和血管生成生物标志物之间的关联进行了横断面分析。我们进一步通过斯皮尔曼部分相关分析探索了这些途径中的新型生物标志物之间的关联。我们假设吡哆醛-5'-磷酸（PLP）与炎症生物标志物呈负相关。我们观察到 PLP 与 C 反应蛋白（CRP）（r=-0.33，Plinear <0.0001）、血清淀粉样蛋白 A（SAA）（r=-0.23，Plinear=0.003）、白细胞介素-6（IL-6）（r=-0.39，Plinear <0.0001）、白细胞介素-8（IL-8）（r=-0.20，Plinear=0.02）和肿瘤坏死因子-α（TNFα）（r=-0.12，Plinear=0.045）呈负相关。在 CRC 患者中，也观察到 5-甲基四氢叶酸与 CRP（r=-0.14）、SAA（r=-0.14）和 TNFα（r=-0.15）之间的类似相关性。叶酸代谢物乙酰-对氨基苯甲酰谷氨酸（pABG）与白细胞介素-6（r=0.27，Plinear <0.0001）呈正相关，与白细胞介素-8（r=0.21，Plinear <0.0001）呈正相关，表明炎症期间叶酸利用率较高。我们的数据支持 PLP 与 CRC 患者炎症生物标志物呈负相关的假设。更好地了解 PLP 和其他一碳代谢物在结直肠癌变和预后中的炎症过程中的作用和相互关系，可以确定未来 CRC 患者饮食指导的目标。
