Rectal mucosal proliferation, dietary factors, and the risk of colorectal adenomas

Colorectal cancer arises from a series of precursor stages, the so called adenoma-carcinoma sequence. Increased rectal mucosal proliferation may be an early step in this sequence. Because dietary factors are implicated in the etiology of colorectal cancer, one might predict that diet would also be associated with proliferation. We conducted this study to examine the association of diet with rectal mucosal proliferation. Rectal mucosal proliferation was measured in endoscopic biopsy specimens by proliferating cell nuclear antigen (PCNA) immunohistochemistry and whole crypt mitotic counts (WCMCs). Diet was evaluated using a validated quantitative food frequency questionnaire. The correlation between PCNA labeling index (LI) and WCMCs was determined using Kendall's tau, a nonparametric measure of correlation. Logistic regression was used to examine the effect of proliferation on adenoma status, controlling for confounders. The relationship between proliferation and dietary and demographic factors was examined using linear regression. There were 308 patients who had one or both measures of proliferation. There was no significant correlation between PCNA LI and WCMCs (Kendall's tau = 0.04; P = 0.35). Neither measure of proliferation was predictive of adenoma status, even after adjusting for potential confounders. Body mass index and calories per day were significant predictors of WCMC (P = 0.01 and P = 0.03, respectively). PCNA labeling index was not associated with any dietary variables, although its association with dietary fat nearly reached statistical significance (P = 0.09). The association between proliferation and diet were generally inconsistent. There appears to be no simple relationship between colorectal cancer risk factors, colorectal adenomas, and these two measures of rectal mucosal proliferation. We need simpler, more reliable intermediate markers for use in etiological and intervention studies.