Dietary Components Modify Gene Expression: Implications for Carcinogenesis

Abstract

Mouse genetic models that probe important pathways in intestinal cell maturation, such as cell-cycle regulation, apoptosis, and, especially, lineage specific differentiation, have provided profound insight into the underlying mechanisms of intestinal tumor formation and progression. However, a wealth of epidemiological and experimental data indicates that environment, especially the diet, is a principal determinant of relative risk for tumor development. We have demonstrated that even in mouse models in which tumor incidence is strongly initiated by genetic manipulation of genes, such as Apc, p21(WAF1/cip1), and p27(Kip1), a Western-style diet that is high in fat and low in calcium and vitamin D can dramatically increase and accelerate tumor formation. Moreover, experiments show that modulation of calcium and vitamin D levels can substantially influence tumor formation in both the mouse genetic models, as well as in a new dietary model that appears to mimic the development of sporadic colon cancer. Finally, analysis of gene expression profiles provides important insights into how diets may alter metabolic profiles and regulatory pathways that influence probability of tumor formation in the histologically and physiologically normal intestinal mucosa.

Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials

“…In the last decade, excellent reviews have been published about omega-3 FAs as chemopreventive agents able to interfere with colon cancer pathways signaling. The etiology of CRC is a multifactorial process, which includes specific oncogene mutations, tumor suppressor genes, environmental factors and lifestyle, especially diet habits [122]. DHA suppresses the proliferation, induces apoptosis in colon cancer cells in vitro and decreases the formation and growth of induced tumors in vivo.…”

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

“…The pathogenesis of CRC is a long and multifactorial process which involves mutations in specific oncogenes and tumour suppressor genes and alterations in gene expression which are induced by epigenetic and non-genotoxic mechanisms 46 . This process is significantly influenced by environmental factors and lifestyle, especially diet composition 47 . Experimental studies have shown that DHA functions as a potent suppressor of colon cancer cell proliferation in vitro 48 as well as in vivo 49 , simultaneously inducing cell death in a dose-and time-dependent manner 50 .…”

Epigenetics and Pancreatic Cancer: The Role of Nutrigenomics

“…In the nutritional field, epigenetics is important because nutrients and bioactive food components can modify the expression of genes at the transcriptional level (91)(92)(93). There is a critical lack of research examining the role of critical nutrients on the etiology of cancers such as pancreatic cancer, although animals studies have indicated its role in cancer development for a number of years (94,95).…”