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Biomarkers and Early Detection: Risk Markers and Surrogate Endpoints

Expression of APC in normal-appearing rectal mucosa differs between those with and without incident, sporadic colorectal adenomatous polyps and may be modulated by diet: Results from the markers of adenomatous polyps II (MAP II) case-control study.

Emory University, Atlanta, GA

Abstract

A13

Background : Mutation in the APC tumor suppressor gene, resulting in inactivation of the "APC pathway", occurs in 80% of sporadic colon carcinomas. Expression of APC in normal colonic mucosa may differ between subjects with and without adenomas, and serve as a potential biomarker for risk of adenomas and hence sporadic colon carcinoma. Methods : We conducted a colonoscopy-based case-control study, comprising 49 cases with adenomas and 152 controls between the ages of 30 and 74 years, in Columbia, South Carolina between January and December 2003. We measured APC using automated immunohistochemistry and quantitative image analysis software in a randomly selected subset consisting of 42 cases and 45 controls. We log transformed the values and used t-tests to compare differences in expression between cases and controls. We used multivariable logistic regression to explore associations of APC expression with environmental, clinical, and nutritional risk factors. Results : Mean levels of log-transformed APC expression were lower in cases than in controls; the proportional difference in mean values between cases and controls was -21% (p = 0.60). Cases had higher total intakes of fat than controls (OR 1.02; 95% CI 1.005-1.03; p = 0.01). In a logistic regression model, controlling for age, sex, and total fat intake, cases had lower expression of APC than controls (OR 0.77; 95% CI 0.49-1.19; p = 0.59). Among those with higher fat intake, cases had much lower APC expression than controls (OR 0.48; 95% CI 0.20, 1.11; p = 0.08). Among men, controlling for age, total fat intake and family history of CRC, cases had a significantly lower expression of APC compared to controls (OR 0.42; 95% CI 0.18- 0.96; p = 0.04). There were trends in the direction of higher APC expression among those with higher total intakes of calcium (OR 1.28; 95% CI 0.82- 1.98; p = 0.3) and vitamin D (OR 1.21; 95% CI 0.78-1.89; p = 0.2). Conclusion: These results suggest that APC expression in normal-appearing rectal tissue in humans can be quantitatively measured, and that this potential biomarker is influenced by modifiable dietary and other lifestyle risk factors for colorectal cancer. Thus, it may serve as a biomarker of risk for colorectal neoplasms, and is a putative target for chemoprevention.