Nutrient-gene interaction: metabolic genotype-phenotype relationship.
ABSTRACT The U.S. Department of Health and Human Services (DHHS)/USDA Dietary Guidelines for Americans is a science and population evidence-based guide on diet and physical activity, providing advice and recommendations to promote a healthier lifestyle and reduce the risk of chronic diseases, including cancer. These recommendations are supported by the comprehensive evidence-based review on diet and cancer prevention conducted by the American Institute for Cancer Research, National Cancer Institute, World Health Organization/International Agency for Research on Cancer, and others. However, influencing dietary effects are the individual genetic predispositions that are the basis for considerable interindividual variations in cancer risk within the population and in nutrient homeostasis, which is maintained by genomic-nutrient and metabolic-phenotype interactions. Although genetics is an important component, it accounts for only a portion of this variation. An individual's overall phenotype, including health status, is achieved and maintained by the sum of metabolic activities functioning under differing circumstances within the life cycle and the complex interactions among genotype, metabolic phenotype, and the environment. In this postgenomic era, high-throughput groups of technologies in genomics, proteomics, and metabolomics measure and analyze DNA sequences, RNA transcripts, proteins, and nutrient-metabolic fluxes in a single experiment. These advances have transformed biomarker studies on nutrient-gene interactions from a reductionist concept into a holistic practice in which many regulated genes involved in metabolism, along with its metabolic phenotypes, can be measured through functional genomics and metabolic profiling. The overall integration of data and information from the building blocks of metabolism-based nutrient-gene interaction can lead to future individualized dietary recommendations to diminish cancer risk.
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ABSTRACT: There is much current interest in how biological systems respond to environmental changes. In this article, we address this question from a theoretical systems biology perspective. Specifically, we examine linear enzyme pathways, including all processes from transcription to enzyme action, and incorporating biologically-realistic negative feedback in the form of competitive inhibition. We investigated how steady state biomarker concentrations changed in response to variable rates of precursor material inflow across genetically variable systems, with alleles conferring different expression rates. We observed a non- equivalence of response across these systems, implying a gene-environment interaction. Furthermore, we observed that total variance in populations of systems increased dramatically in response to increased precursor material influx. These results imply that gene-environment interaction effects are likely to occur at the most basic levels of biological organization, even in the presence of negative feedback.BioMedical Engineering and Informatics, 2008. BMEI 2008. International Conference on; 06/2008
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ABSTRACT: Pancreatic cancer is one of the most aggressive malignancies in US adults. Experimental studies have found that antioxidant nutrients could reduce oxidative DNA damage, suggesting that these antioxidants may protect against pancreatic carcinogenesis. Several epidemiologic studies showed that dietary intake of antioxidants was inversely associated with the risk for pancreatic cancer, demonstrating the inhibitory effects of antioxidants on pancreatic carcinogenesis. Moreover, nutraceuticals, the anticancer agents from diet or natural plants, have been found to inhibit the development and progression of pancreatic cancer through the regulation of cellular signaling pathways. Importantly, nutraceuticals also up-regulate the expression of tumor-suppressive microRNAs (miRNAs) and down-regulate the expression of oncogenic miRNAs, leading to the inhibition of pancreatic cancer cell growth and pancreatic cancer stem cell self-renewal through modulation of cellular signaling network. Furthermore, nutraceuticals also regulate epigenetically deregulated DNAs and miRNAs, leading to the normalization of altered cellular signaling in pancreatic cancer cells. Therefore, nutraceuticals could have much broader use in the prevention and/or treatment of pancreatic cancer in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are needed to realize the true value of nutraceuticals in the prevention and/or treatment of pancreatic cancer.Pancreas 01/2015; 44(1):1-10. DOI:10.1097/MPA.0000000000000257 · 3.01 Impact Factor
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ABSTRACT: A centenary review presents an opportunity to ponder over the processes of concept development and give thought to future directions. The current review aims to ascertain the ontogeny of current concepts, underline the connection between ideas and people and pay tribute to those pioneers who have contributed significantly to modelling in animal nutrition. Firstly, the paper draws a brief portrait of the use of mathematics in agriculture and animal nutrition prior to 1925. Thereafter, attention turns towards the historical development of growth modelling, feed evaluation systems and animal response models. Introduction of the factorial and compartmental approaches into animal nutrition is noted along with the particular branches of mathematics encountered in various models. Furthermore, certain concepts, especially bioenergetics or the heat doctrine, are challenged and alternatives are reviewed. The current state of knowledge of animal nutrition modelling results mostly from the discernment and unceasing efforts of our predecessors rather than serendipitous discoveries. The current review may stimulate those who wish for greater understanding and appreciation.The Journal of Agricultural Science 04/2008; 146(02). DOI:10.1017/S0021859608007703 · 2.89 Impact Factor