Effects of milk and milk products on rectal mucosal cell proliferation in humans

Intake of dairy products and major dairy constituents (e.g., calcium) has been proposed to reduce the risk of colorectal cancer, although epidemiological studies have yielded inconclusive results. We conducted a randomized cross-over trial to test the effects of high- and low-dairy consumption diets on rectal mucosal proliferation, a possible intermediary marker for large bowel cancer. From a gastroenterology clinic at an academic medical center, we recruited 40 patients, ages 25-79 years, who had either a history of a large bowel adenoma or a first-degree relative with large bowel cancer. Participants completed a baseline questionnaire covering demographic characteristics, health history, and habits and a food frequency questionnaire. They were randomized to a 12-week diet of either high dairy intake (six dairy servings/day) or low dairy intake (<0.5 serving of dairy products/day), with an intervening 12-week washout period in which they were asked to resume their usual diet before crossing over to the alternate study diet for the last 12-week period of the study. Adherence to the study diets was monitored by a daily dairy intake checklist and periodic, unscheduled 24-h dietary recalls. Biopsies of the rectal mucosa were obtained at the beginning and end of each intervention phase. Two assays of rectal mucosal cell proliferation were performed: immunohistochemical determination of proliferating cell nuclear antigen and whole crypt mitotic count. We found no statistically significant changes in either of these proliferation measures as a result of high or low dairy intake. There was no correlation between the labeling index for proliferating cell nuclear antigen and whole crypt mitotic count; however, measures of the location and intensity of cell proliferation within the rectal crypt were highly correlated between the two assays. Thus, our study indicates that greater consumption of dairy products over a 12-week period does not change rectal mucosal cell proliferation.