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. 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

Nicholas J W Rattray  1 , Georgia Charkoftaki  1 , Zahra Rattray  2 , James E Hansen  2   3 , Vasilis Vasiliou  1 , Caroline H Johnson  1
Affiliations

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

Nicholas J W Rattray et al. Curr Pharmacol Rep. 2017 Jun.

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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Conflict of interest statement

Disclosure There are no conflicts of interests within this article.

Figures

Figure 1
Figure 1
Metabolomics within the gene-environmental continuum. The causation of most cancers resides at the interface of genetic and environmental exposure. By using multiple platforms, a more comprehensive analysis of the effects the exposome plays on cancer phenotype can be assessed. By analyzing the downstream metabolic products of this modulated gene expression, metabolomics can be used to refine mechanistic understanding of exposure whilst also potentially identifying novel biomarkers. Adapted from (138).
Figure 2
Figure 2
The biochemical breakdown of ethanol is dependent on genetic polymorphisms in the ethanol and folate metabolic pathways. Many consecutive enzymes play important roles in maintaining redox homeostasis and protecting the cells from oxidative stress but dysregulation within these systems can lead to the formation of reactive oxygen species (ROS) that can damage cellular components.
See this image and copyright information in PMC

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