Nutrigenomic approach to understanding the mechanisms by which dietary long-chain fatty acids induce gene signals and control mechanisms involved in carcinogenesis

Abstract

Nutrigenomic approaches are enhancing our understanding of how dietary lipids affect cell signaling and carcinogenesis. Novel technologies such as microarrays and Serial Analysis of Gene Expression (SAGE) allow the simultaneous measurement of mRNA expression levels of hundreds or thousands of genes. These are the forerunner genomic technologies currently being applied to nutrition; however, they are increasingly being combined with other global analytical emerging strategies including proteomics and metabolomics. Lipids are components of most foods. Aside from their principal dietary role of delivering energy to the body, dietary lipids are involved in normal and aberrant mitogenic processes and have been linked to the development and progression of colon cancer, colon carcinogenesis, hepatocarcinogenesis, breast cancer, and mammary carcinogenesis and metastasis. Lipids influence multiple signaling pathways involved in disease progression, some of which are difficult to study with a single gene, protein, or biomarker approach. Therefore, the mechanisms by which lipids influence cancer are for the large part unknown, partly due to the lack of research tools that can adequately cover the complex mechanisms involved. Long-chain polyunsaturated fatty acids (LC-PUFA) are probably the most commonly studied dietary lipids with respect to their effects on carcinogenesis. The effects of diets high in LC-PUFA have been studied for decades. Bougnoux1 extensively reviewed the influence of LC-PUFAs on cancer and carcinogenesis. The inhibitory effects of fish oil, which is rich in -3 LC-PUFA, on carcinogenesis have been shown in various models including an azoxymethane-induced rat colon carcinogenesis model and an HT29 colon tumor growth and metastasis nude mouse model.2,3 Although cell culture and animal studies support a preventive action of LC-PUFA, there is divided opinion on the association between LC-PUFA intake and cancer risk in humans. For example, case control, international comparisons, and animal studies have suggested an association between fat intake and breast cancer incidence, but cohort studies have not reported this association.4 Recent studies have applied nutrigenomic approaches to better elucidate the complex cell regulation processes affected by LCPUFAs.5–7 In this review we describe a few selected mechanisms through which LC-PUFA can affect carcinogenesis and then review studies that used a nutrigenomics approach to study LCPUFA effects on carcinogenesis.