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.

中文翻译：

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结直肠癌患者中的一碳代谢物、B 族维生素以及与全身炎症和血管生成生物标志物的关联：ColoCare 研究的结果


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（例如结直肠癌 (CRC)）的发展有关。然而，一碳代谢在结直肠癌患者炎症和血管生成中的作用仍不清楚。本研究的目的是调查海德堡前瞻性 ColoCare 研究中新诊断的 CRC 患者 (n 238) 的一碳代谢成分与炎症和血管生成生物标志物的关联。我们使用多元线性回归模型对来自术前血清样本的 12 种 B 族维生素和一碳代谢物以及 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。我们通过 Spearman 偏相关分析进一步探讨了这些通路中新型生物标志物之间的关联。我们假设 5'-磷酸吡哆醛 (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，P线性 < 0·0001)、血清淀粉样蛋白 A (SAA) (r –0·23，P线性 = 0·003) 呈负相关， IL-6（r –0·39，P线性 < 0·0001）、IL-8（r –0·20，P线性 = 0·02）和 TNFα（r –0·12，P线性 = 0·045）。在 CRC 患者中，5-甲基四氢叶酸和 CRP (r –0·14)、SAA (r –0·14) 和 TNFα (r –0·15) 也观察到类似的结果。叶酸分解代谢物乙酰基对氨基苯甲酰谷氨酸 (pABG) 与 IL-6 呈正相关（r 0·27，P线性 < 0·0001），pABG 与 IL-8 呈正相关（r 0·21，P线性 <） 0·0001)，表明炎症期间叶酸利用率较高。我们的数据支持 CRC 患者中 PLP 与炎症生物标志物之间呈负相关的假设。 更好地了解 PLP 和其他一碳代谢物与结直肠癌发生和预后中炎症过程的作用和相互关系，可以为结直肠癌患者未来的饮食指导确定目标。