Janice Drew's work on diet and cancer

Abstract

Obesity and associated reduced consumption of plant derived foods are linked to increased risk of colon cancer as well as a number of other organ specific cancers. Inflammatory processes are a contributing factor but the precise mechanisms remain elusive. Obesity and cancer incidence are increasing worldwide, presenting bleak prospects for reducing, or preventing, obesity related cancers. The incidence of these preventable cancers can be achieved with greater understanding of the molecular mechanisms linking diet and carcinogenesis. Janice Drew has developed a research program over recent years to investigate molecular mechanisms related to consumption of anti-inflammatory metabolites generated from consumption of plant based diets, the impact of high fat diets and associated altered metabolism and obesity on regulation of colon inflammatory responses and processes regulating the colon epithelium. Comprehensive strategies have been developed incorporating transcriptomics, including the novel gene expression technology, the GenomeLab System and proteomics, together with biochemical analyses of plasma and tissue samples to assess correlated changes in oxidative stress, inflammation and pathology. The approaches developed have achieved success in establishing antioxidant and anti-inflammatory activity of dietary antioxidants and associated genes and pathways that interact to modulate redox status in the colon. Cellular processes and genes altered in response to obesity and high fat diets have provided evidence of molecular mechanisms that are implicated in obesity related cancer.

Keywords: Adipokines; Diet and cancer; Leptin; Mitochondria; Multiplex gene expression; Obesity-related cancer; Phenolic acids; Proteomics.

Figure 1

Dr. Janice Drew, PhD, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, United Kingdom

Figure 2

Obesity cancer links. Obesity and colon cancer are both associated with increased consumption of diets rich in saturated fats, together with reduced consumption of fruit, vegetables and fibre. Consumption of high fat diets and diets deficient in fruit, vegetables and fibre promotes metabolic stress. This is manifested by increased oxidative stress and inflammatory responses, altered levels of adipokines, insulin and triglycerides and changes in protein profiles of mitochondrial multiple protein expression forms (MPEFs). Research investigating the metabolic changes associated with obesity is elucidating molecular mechanisms linked to associated increased cancer risk

Figure 3

Application of a custom designed multiplex of inflammatory cytokines associated with early events in colon carcinogenesis. GeXP profiling generates gene expression signatures to reveal molecular characteristics associated with pathology. GeXP facilitates a rapid analysis of multiple gene targets simultaneously and is feasible for analysis of small tissue biopsy samples (either fresh or frozen archived tissues) available from clinical specimens since only nanogram quantities of total RNA are required. Custom designed multiplex GeXP assays present opportunities to conduct gene regulatory studies in response to dietary metabolites and links with pathology. Studies in our lab are focused on clinical applications of novel custom designed assays to identify signature gene expression profiles and biomarkers of dysplasia, identification of novel disease sub-types and responses to dietary intervention and therapeutics.