Strategies for dietary intervention studies in colon cancer

Abstract

As a result of many studies in descriptive and analytic epidemiology, in animal carcinogenesis, and in the direct examination of body fluids for mutagens/carcinogens, it is possible to develop a list of dietary factors that may be associated with the high rate of colon cancer and related cancers in Western countries. This paper is concerned with the design of intervention studies to clarify which of these factors is important. The size of such intervention trials is influenced primarily by two factors: the incidence of the disease outcome studied in a control population and the magnitude of risk reduction in a treated group. Calculations based on a variety of assumptions suggest that a randomized trial in which cancer mortality is measured as the outcome of the intervention in a healthy population is probably too costly to be justified by current evidence linking the disease to diet. However, precursor lesions can be considered as an alternative outcome. The choice of the precursor lesion depends on the link to the disease in question, the prevalence of the lesion in the population, and the ease of detection. Recent developments in the application of endoscopic methods and in the description of the pathologic process leading to cancer suggest the use of gastrointestinal polyps as "precursor lesions" as the outcome of a trial. We illustrate these points with a protocol for a study in progress, a randomized double-blind study of the effect of ascorbic acid and alpha-Tocopherol on the rate of recurrence of colorectal polyps.

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

“…This may have been a consequence of the cumbersome method that has been used to test possible interventions. The primary approach used has been randomised controlled trials in which the end point was the appearance of colonic polyps (Bruce et al, 1981). These tumours take years to develop and many subjects are needed to yield significant results.…”

n‐3 fatty acids decrease colonic epithelial cell proliferation in high‐risk bowel mucosa

“…Colorectal adenomatous polyps with abnormal cell-kinetics characteristics has been suggested to be putative precursor lesions to carcinoma (14). Bruce et al (15) and Lippmann et al (16) showed that hyperproliferation of colonic epithelium is an appropriate intermediate end-point for chemopreventive intervention.…”

Diet and colorectal cancer with special reference to fiber intake

“…There has been considerable interest in the potential association of diet and colorectal cancer (Graham and Mettlin, 1979;Jain et al, 1980;Zaridze, 1981Zaridze, , 1983Bruce et al, 1981;Miller et al, 1983;McKeown-Eyssen and Bruce, 1985; Kolonel, 1987). Dietary fiber has been studied in this respect, as well as fat, protein, micronutrients, cruciferous vegetables, and other selected food groups.…”