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与癌症预防相关的营养素的分子靶点。

Molecular targets for nutrients involved with cancer prevention.

作者信息

Milner J A, McDonald S S, Anderson D E, Greenwald P

机构信息

Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA.

出版信息

Nutr Cancer. 2001;41(1-2):1-16. doi: 10.1080/01635581.2001.9680606.

Abstract

Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention.

摘要

膳食营养素可通过多种作用机制抑制或促进致癌作用,从而影响癌症风险。四十多年来,确定其作用位点并阐明其作用机制一直是营养与癌症研究的重点。将营养与癌症研究从主要的观察性方法转变为分子方法,为真正识别哪些人会从膳食干预策略中受益、哪些人不会受益提供了令人兴奋的机会。营养基因组学这一新兴领域(本文定义为对任何与营养素的基因或表观遗传相互作用的研究)将是这一演变的关键。弄清楚哪些基因上调或下调会导致随后的表型变化并非易事。有证据表明,基因多态性可影响营养素与分子靶点之间的动态关系,进而导致个体间反应的差异。由于可能会识别出许多分子靶点,因此可能有必要对营养素进行鉴定,即确定哪些与营养素相关的特定基因和表观遗传变化会引起表型变化,以确定哪些相互作用最为重要以及在何种情况下最为重要。重点介绍了维生素D、钙、叶酸、硒、染料木黄酮和白藜芦醇,因为它们代表了特定类别的营养素,并说明了对各种营养素进行鉴定以了解其在癌症预防中的生理意义的必要性。随着营养科学的不断发展,人们将更清楚地了解营养素如何通过分子相互作用调节癌症风险,以及农艺方法和/或生物技术如何改变食物。不可否认,采用新的基因组技术为营养领域的广泛进展,尤其是与癌症预防相关的进展,提供了令人兴奋的机会。

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