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氨基酸与结肠癌腺瘤风险:一项孟德尔随机化研究。

Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study.

机构信息

Cancer Clinical Research Ward, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China.

Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China.

出版信息

BMC Cancer. 2023 Oct 28;23(1):1041. doi: 10.1186/s12885-023-11514-w.

DOI:10.1186/s12885-023-11514-w
PMID:37898769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10612249/
Abstract

BACKGROUND

The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of colon adenocarcinoma remains largely unexplored.

METHODS

We utilized Mendelian randomization (MR) analysis to examine the association between 20 amino acids in the blood and the risk of colon adenocarcinoma. Additionally, reverse MR analysis was employed to identify the presence of reverse causality. A two-step MR analysis was conducted to ascertain the potential mediating effect. Lastly, the alanine detection data from colon adenocarcinoma patients in our hospital were utilized to investigate the differences in alanine levels among healthy individuals and patients with colon cancer, as well as among patients with different stages and locations of colon cancer. Furthermore, a Kaplan-Meier curve was employed to examine the correlation between alanine and overall survival, followed by the implementation of COX univariate analysis.

RESULTS

The results of our study indicate that there is an inverse correlation between alanine and the risk of colon adenocarcinoma. Additionally, we found no significant evidence to support a causal relationship between colon adenocarcinoma and alanine. Furthermore, our analysis revealed that alanine aminotransferase (ALT) and blood glucose do not act as mediators in this causal pathway. Moreover, individuals diagnosed with colon adenocarcinoma exhibited a significant decrease in alanine levels, particularly in cases of stage IV colon adenocarcinoma with distant metastasis. Additionally, elevated alanine levels were associated with improved overall survival rates among colon adenocarcinoma patients.

CONCLUSIONS

The results of this study indicate that alanine exhibits protective characteristics against the onset of colon adenocarcinoma and may play a role in promoting a more favorable disease prognosis. Consequently, dietary interventions aimed at increasing alanine intake may serve as a potential strategy for the prevention and treatment of colon adenocarcinoma.

摘要

背景

肿瘤细胞中氨基酸代谢重编程的存在已得到充分证实。然而,血液氨基酸与结直肠腺癌风险之间的潜在相关性在很大程度上仍未得到探索。

方法

我们利用孟德尔随机化(MR)分析来研究血液中 20 种氨基酸与结直肠腺癌风险之间的关联。此外,还进行了反向 MR 分析以确定是否存在反向因果关系。采用两步 MR 分析来确定潜在的中介效应。最后,我们利用我院结直肠腺癌患者的丙氨酸检测数据,研究健康个体与结直肠癌患者、不同结直肠癌分期和部位患者之间的丙氨酸水平差异。此外,还绘制了 Kaplan-Meier 曲线来研究丙氨酸与总生存期之间的相关性,随后进行 COX 单因素分析。

结果

我们的研究结果表明,丙氨酸与结直肠腺癌风险呈负相关。此外,我们没有发现结直肠癌与丙氨酸之间存在因果关系的显著证据。此外,我们的分析表明,丙氨酸氨基转移酶(ALT)和血糖在该因果途径中不起中介作用。此外,诊断为结直肠腺癌的个体丙氨酸水平显著降低,尤其是伴有远处转移的 IV 期结直肠腺癌患者。此外,升高的丙氨酸水平与结直肠腺癌患者的总生存率提高相关。

结论

本研究结果表明,丙氨酸对结直肠腺癌的发生具有保护作用,可能在促进更有利的疾病预后方面发挥作用。因此,增加丙氨酸摄入的饮食干预可能是预防和治疗结直肠腺癌的一种潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/6bc5b8fbd9bb/12885_2023_11514_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/938c727cc679/12885_2023_11514_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/3286e4fcd3e0/12885_2023_11514_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/d85b6f0f1258/12885_2023_11514_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/6bc5b8fbd9bb/12885_2023_11514_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/938c727cc679/12885_2023_11514_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/3286e4fcd3e0/12885_2023_11514_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/d85b6f0f1258/12885_2023_11514_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b088/10612249/6bc5b8fbd9bb/12885_2023_11514_Fig4_HTML.jpg

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