There is considerable basic science research to suggest that isothiocyanates (ITC) or several indole analogs (e.g., indole-3carbinol (I3C)) slow cellular proliferation, re-instate apoptotic action, and reduce colon tumor incidence. Humans are exposed to these agents primarily through consuming Brassica vegetables (e.g., broccoli), but it is unknown if greater Brassica consumed could affect colon cancer risk. We propose a short-term pilot dietary intervention to investigate the effects of greater Brassica consumption on markers colon cancer progression. Twenty adenoma patients will participate in a randomized controlled cross-over trial. Recruitment, intervention, and lab protocols have been developed through other on-going studies, improving the cost-efficiency of this pilot project. The intervention-arm of the trial is based on a model developed for the Women's Health Initiative, and provides social support and information to help participants incorporate these vegetables into their daily diet. Biomarkers measured from rectal biopsies will include Bcl-2 (inhibits apoptosis), Bak and Bax (promote apoptosis), Mib-1 (marker of cellular proliferation), and p21 (marker of cellular differentiation). Multiple 24-hour dietary recalls will measure each participant's adherence to the intervention. Dietary adherence will be measured further by urinary ITC level (combined with GST enzyme genotype), a unique and specific biomarker of Brassica vegetable intake. Using mixed-model repeated-measures ANOVA, we will compare molecular marker expression when participants consume Brassica vegetables to when these same participants consume an over-the-counter fiber and vitamin supplement. This pilot study will provide the needed estimates of variance in biomarker response to the dietary change for sample size calculations for future applications. Previously, we found that healthy people were able to increase the consumption of these vegetables with minimal social and instructional support, and we used those pilot data to gain funding for a larger randomized trial enrolling breast cancer survivors. Since Brassica vegetables are widely available, inexpensive, and consumed without harm, a change in molecular marker expression consistent with reduced proliferation and enhanced differentiation and apoptosis would suggest further research to evaluate the application of Brassica consumption to reduce colon cancer risk.
