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 crosssectional 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. adjusted OR, 3.74; 95% CI,). 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. (Cancer Epidemiol Biomarkers Prev 2008;17(2):306 -10)

Association between Rectal Optical Signatures and Colonic Neoplasia: Potential Applications for Screening

“…Our studies on the effect of previous adenomas are inconclusive but potentially suggest contributions from both longer term field carcinogenesis and tumor-related factors analogous to our data for microvascular blood content (38). Other groups have shown that rectal apoptosis rate predicts future development of neoplasia, suggesting that the markers of field carcinogenesis may reflect immediate as well as long-term risk (44). Thus, the utility of rectal LEBS for postpolypectomy surveillance will need to be determined.…”

Apoptosis in the Colonic Crypt, Colorectal Adenomata, and Manipulation by Chemoprevention

“…A recent study having previously measured the levels of apoptosis (using morphology from H&E stained specimens) within the normal rectal mucosa of patients attending for colonoscopy for a variety of reasons, but without colitis, familial adenomatous polyposis (FAP), previous colorectal cancer resection, previous colon cancer or adenoma, then correlated this previously measured apoptosis score with the number, size, histological type, and degree of atypia of polyps found at a subsequent follow-up colonoscopy (54). The followup population included patients with polyps at baseline who returned for follow-up of these, and patients without polyps at baseline but who were scheduled for a clinically indicated colonoscopy.…”

“…The findings were of an inverse relationship between apoptosis and the development of new adenomas, and subjects in the highest tertile of apoptosis were less likely to have adenoma recurrence. Because some patients who initially do not show adenomas will develop them in the future, but will be unlikely to enter surveillance programs because of the lack of an index polyp, it was suggested therefore by the authors, that apoptosis might be used to asses risk of future polyp development, but added that the current methods to assess apoptosis are too ''tedious'' to be clinically useful (54).…”

Suppressor of cytokine signaling 3 (SOCS3) is not an independent biomarker of colorectal adenoma risk

“…Our group has shown that patients with adenoma have reduced apoptosis in their normal mucosa, demonstrating a field effect that predisposes the individual to a higher risk of developing precancerous adenomas [14,15]. We hypothesized that SOCS3 might be a good biomarker of colorectal neoplasia risk, but contrary to expectation the study was negative.…”