- Rectal epithelial proliferation (REP) measurements are used as a biomarker of risk for colorectal neoplasia and response to chemoprevention. The authors evaluated REP in screenees with and without a history of adenoma and its association with demographic and adenoma characteristics, diet, and other lifestyle habits. Long term lifestyle habits were evaluated and proliferation assessed by in vitro bromodeoxyuridine labeling of rectal biopsies in 223 screenees, 132 of whom had adenomas removed > 3 years previously. Analyses included the total population, screenees with a previous history of adenomas and adenoma free screenees separately, and a subgroup of 55 matched adenoma cases and controls. Crypt proliferation measurements were not elevated in screenees with a history of adenomas compared with adenoma free screenees (mean total labeling index [LI] of 4.8% and 4.9%, respectively). This was confirmed by the case-control analysis, in which the LI of the most superficial crypt compartment was lower in the adenoma cases (P=0.05). Moreover, their total LI correlated negatively with the number of adenomas removed previously (P < 0.01). Proliferation was more frequent in the most superficial crypt compartments of female adenoma free screenees than in female screenees with a history of adenomas (P=0.02), and in men age > 65 years compared with younger men (P=0.06). In the total population, negative Spearman rank correlations were found between total LI and long term dietary intake of calcium (correlation coefficient [r]=-0.15; P=0.02), LI of the two most superficial crypt compartments and intake of fiber (r=-0.18; P=0.01), water (r=-0.12; P=0.08), and carbohydrates (not significant). A positive correlation was found between LI of the most superficial crypt compartment and cigarette smoking (r=0.4; P=0.02). REP measurements did not discriminate between screenees with a history of adenomas and adenoma free screenees. Long-term lifestyle habits, gender, and age were associated with REP levels and need to be considered when evaluating human intervention studies.