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首页> 外文期刊>Journal of Personalized Medicine >Gene-Metabolite Interaction in the One Carbon Metabolism Pathway: Predictors of Colorectal Cancer in Multi-Ethnic Families
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Gene-Metabolite Interaction in the One Carbon Metabolism Pathway: Predictors of Colorectal Cancer in Multi-Ethnic Families

机译：一个碳代谢途径中的基因-代谢物相互作用：多族裔家庭大肠癌的预测因子。

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For personalized healthcare, the purpose of this study was to examine the key genes and metabolites in the one-carbon metabolism (OCM) pathway and their interactions as predictors of colorectal cancer (CRC) in multi-ethnic families. In this proof-of-concept study, we included a total of 30 participants, 15 CRC cases and 15 matched family/friends representing major ethnic groups in southern California. Analytics based on supervised machine learning were applied, with the target variable being specified as cancer, including the ensemble method and generalized regression (GR) prediction. Elastic Net with Akaike’s Information Criterion with correction (AICc) and Leave-One-Out cross validation GR methods were used to validate the results for enhanced optimality, prediction, and reproducibility. The results revealed that despite some family members sharing genetic heritage, the CRC group had greater combined gene polymorphism-mutations than the family controls ( p 0.1) for five genes including MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, and DHFR 19bp. Blood metabolites including homocysteine (7 μmol/L), methyl-folate (40 nmol/L) with total gene mutations (≥4); age (51 years) and vegetable intake (2 cups), and interactions of gene mutations and methylmalonic acid (MMA) (400 nmol/L) were significant predictors (all p 0.0001) using the AICc. The results were validated by a 3% misclassification rate, AICc of 26, and 99% area under the receiver operating characteristic curve. These results point to the important roles of blood metabolites as potential markers in the prevention of CRC. Future intervention studies can be designed to target the ways to mitigate the enzyme-metabolite deficiencies in the OCM pathway to prevent cancer.
机译：对于个性化医疗保健，本研究的目的是检查单碳代谢（OCM）途径中的关键基因和代谢物以及它们在多族裔家庭中作为大肠癌（CRC）预测因子的相互作用。在此概念验证研究中，我们总共包括30名参与者，15名CRC病例和15名匹配的家人/朋友，分别代表南加州的主要种族。应用了基于监督机器学习的分析，将目标变量指定为癌症，包括集成方法和广义回归（GR）预测。带有Akaike的信息校正标准（AICc）和留一法交叉验证GR方法的Elastic Net用于验证结果，以提高优化性，预测性和可重复性。结果表明，尽管有一些家族成员共享遗传遗产，但对于五个基因，包括MTHFR C677T，MTHFR A1298C，MTR A2756G，MTRR A66G和DHFR 19bp，CRC组具有比家族对照组更大的组合基因多态性突变（p <0.1）。 。血液代谢产物，包括高半胱氨酸（7μmol/ L），叶酸甲酯（40 nmol / L）和总基因突变（≥4）;年龄（51岁）和蔬菜摄入量（2杯），以及基因突变和甲基丙二酸（MMA）（400 nmol / L）的相互作用是使用AICc的重要预测因子（所有p <0.0001）。接收器工作特性曲线下的3％错误分类率，26的AICc和大于99％的面积验证了结果。这些结果表明，血液代谢物作为预防CRC的潜在标志物具有重要作用。可以将未来的干预研究设计为针对减轻OCM途径中的酶代谢缺陷的途径，以预防癌症。

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