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

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

Author information

1
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA, 06520.
2
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Yale University, CT, USA 06520.
3
Yale Cancer Center, Yale School of Medicine, Yale University, New Haven, CT, USA 06520.

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.

KEYWORDS:

acetaldehyde dehydrogenase; alcohol; colorectal cancer; exposome; metabolomics; microbiome

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