Apoptosis in Normal Rectal Mucosa, Baseline Adenoma Characteristics, and Risk of Future Adenomas

Abstract

Low apoptosis in the normal rectal mucosa has been associated with colorectal adenomas in cross-sectional studies. It is unknown whether apoptosis can predict the occurrence of new adenomas. We evaluated whether apoptosis at baseline colonoscopy, as well as patient and adenoma characteristics, could predict future occurrence of adenomas. Study subjects were participants in the Diet and Health Study III, a cross-sectional study of adenoma risk factors between August 1998 and March 2000. At baseline, subjects underwent colonoscopy and provided normal rectal mucosal biopsies to evaluate apoptosis as well as information about diet and lifestyle. The present study includes 257 subjects who returned for follow-up colonoscopy between 2000 and 2005. Apoptosis, number of adenomas, size, and atypia at baseline colonoscopy were evaluated as predictors of new adenomas. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). At baseline, low apoptosis was significantly associated with increased risk of adenomas (P = 0.0001). Compared with those in the lowest tertile, subjects with high apoptosis were less likely to have an adenoma at follow-up (crude OR, 0.25; 95% CI, 0.09-0.65; adjusted OR, 0.29; 95% CI, 0.08-1.06). Having three or more adenomas at baseline was associated with increased risk of new adenomas (crude OR, 2.46; 95% CI, 1.14-5.31; adjusted OR, 3.74; 95% CI, 1.01-13.83). This study suggests that lower apoptosis is associated with increased risk of future adenoma development. If confirmed in larger studies, apoptosis could potentially be used to identify patients at highest risk for developing new adenomas.