Rattray Nicholas J W, Charkoftaki Georgia, Rattray Zahra, Hansen James E, Vasiliou Vasilis, Johnson Caroline H
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.
Curr Pharmacol Rep. 2017 Jun;3(3):114-125. doi: 10.1007/s40495-017-0088-z. Epub 2017 Apr 7.
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.
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.
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.
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。
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。
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。