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结直肠癌病因中的环境影响:代谢组学的前提

Environmental influences in the etiology of colorectal cancer: the premise of metabolomics.

作者信息

Rattray Nicholas J W, Charkoftaki Georgia, Rattray Zahra, Hansen James E, Vasiliou Vasilis, Johnson Caroline H

机构信息

Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA, 06520.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Yale University, CT, USA 06520.

出版信息

Curr Pharmacol Rep. 2017 Jun;3(3):114-125. doi: 10.1007/s40495-017-0088-z. Epub 2017 Apr 7.

Abstract

PURPOSE OF REVIEW

In this review we discuss how environmental exposures predominate the etiology of colorectal cancer (CRC). With CRC being a personalized disease influenced by genes and environment, our goal was to explore the role metabolomics can play in identifying exposures, assessing the interplay between co-exposures, and the development of personalized therapeutic interventions.

RECENT FINDINGS

Approximately 10 % of CRC cases can be explained by germ-line mutations, whereas the prevailing majority are caused by an initiating exposure event occurring decades prior to diagnosis. Recent research has shown that dietary metabolites are linked to a procarcinogenic or protective environment in the colon which is modulated by the microbiome. In addition, excessive alcohol has been shown to increase the risk of CRC and is dependent on diet (folate), the response of microbiome, and genetic polymorphisms within the folate and alcohol metabolic pathways. Metabolomics can not only be used to identify this modulation of host metabolism, which could affect the progression of the tumors but also response to targeted therapeutics.

SUMMARY

This review highlights the current understanding of the multifaceted etiology and mechanisms of CRC development but also highlights where the field of metabolomics can contribute to a greater understanding of environmental exposure in CRC.

摘要

综述目的

在本综述中,我们讨论环境暴露如何在结直肠癌(CRC)的病因中占主导地位。由于CRC是一种受基因和环境影响的个体化疾病,我们的目标是探讨代谢组学在识别暴露、评估共同暴露之间的相互作用以及开发个性化治疗干预措施方面可以发挥的作用。

最新发现

约10%的CRC病例可由种系突变解释,而绝大多数是由诊断前数十年发生的起始暴露事件引起的。最近的研究表明,饮食代谢产物与结肠中的促癌或保护环境有关,这种环境由微生物群调节。此外,过量饮酒已被证明会增加CRC风险,并且取决于饮食(叶酸)、微生物群的反应以及叶酸和酒精代谢途径中的基因多态性。代谢组学不仅可用于识别这种可能影响肿瘤进展以及对靶向治疗反应的宿主代谢调节。

总结

本综述强调了目前对CRC发生发展的多方面病因和机制的理解,但也突出了代谢组学领域可在哪些方面有助于更深入了解CRC中的环境暴露。

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本文引用的文献

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Development of cell metabolite analysis on microfluidic platform.微流控平台上细胞代谢物分析的发展
J Pharm Anal. 2015 Dec;5(6):337-347. doi: 10.1016/j.jpha.2015.09.003. Epub 2015 Sep 30.
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Cancer Statistics, 2017.《2017 年癌症统计》
CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
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Alcohol and cancer-individual risk factors.酒精与癌症——个体风险因素
Addiction. 2017 Feb;112(2):232-233. doi: 10.1111/add.13664. Epub 2016 Dec 1.
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Diet, microorganisms and their metabolites, and colon cancer.饮食、微生物及其代谢产物与结肠癌
Nat Rev Gastroenterol Hepatol. 2016 Dec;13(12):691-706. doi: 10.1038/nrgastro.2016.165. Epub 2016 Nov 16.

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