COLORECTAL EPITHELIAL-CELL PROLIFERATIVE KINETICS AND RISK-FACTORS FOR COLON-CANCER IN SPORADIC ADENOMA PATIENTS

Colorectal epithelial cell proliferative kinetics are altered in patie nts at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that in cludes the entire crypt (higher empty set(h)). To assess factors assoc iated with LI and empty set(h), we performed a cross-sectional analysi s using baseline rectal mucosal biopsies from sporadic adenoma patient s participating in a chemoprevention trial, Biopsies (taken without pr eparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associa ted proliferating cell nuclear antigen by immunohistochemical methods, High-quality, scorable biopsies were obtained for 115 patients, and u sing analysis of covariance and multiple linear regression, the LI and empty set(h) were evaluated in relation to diet and other lifestyle f actors, demographics, anthropometrics, family history of colon cancer, and polyp history, Statistically significant findings included the fo llowing: (a) The LI for those in the upper versus the lowest tertile o f vegetable and fruit consumption was, proportionately, 35% lower (3.4 % versus 5.3%; P < 0.001); for vitamin supplement users versus nonuser s, it was 36% lower (3.3 versus 5.2%; P < 0.001); for recurrent versus incident polyp patients, it was 36% higher (6.2 versus 4.0%; P < 0.00 1); and for those with rectal polyps only versus those with colon poly ps only, it was 28% higher (6.0 versus 4.3%; P = 0.05); and (b) the em pty set(h) for those in the upper versus the lowest tertile of sucrose consumption was, proportionately, 48% higher (7.1% versus 3.7%; P = 0 .01). These results indicate that (a) colorectal epithelial cell proli feration rates are higher in recurrent adenoma patients than in incide nt adenoma patients and in patients with rectal adenomas only versus t hose with colon adenomas only, but they are lower in patients with hig her intakes of vegetables and fruit and in those who take vitamin/mine ral supplements, and (b) the distribution of proliferating cells is sh ifted toward more inclusion of the upper 40% of the crypt in patients with higher intakes of sucrose, The pattern of positive, negative, and null associations of potential risk factors with cell proliferation i s similar to that commonly found with colonic neoplasms.