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Biomarkers and Early Detection: Risk Markers and Surrogate Endpoints

Aberrant crypt foci (ACF) in an inner city population undergoing routine colorectal cancer (CRC) screening: A prospective study.

UIC, Chicago, IL

Abstract

A17

Background: ACFs are the earliest histopathological lesion associated with malignant transformation in the colon, and are commonly used as a surrogate marker in animal models of CRC. Because of their small size, magnification and the use of vital stains are typically needed to visualize these microscopic structures. In humans, studies to date performed in highly selected populations suggest that ACF# correlates with CRC, but nothing is known about their prevalence and association with environmental risk factors in a general population of patients undergoing standard CRC screening. Methods: We recently devised a novel approach to rapidly enumerate ACF# during endoscopy called magnification chromo-colonoscopy (MCC, Endoscopy 2004; 36: 609). Since 1/05 MCC has been the primary modality offered by the University of Illinois at Chicago (UIC) CRC Screening Clinic, with 457 consecutive exams performed to date (all by REC or RVB). Of these, 83% allowed their clinical and endoscopic information to be evaluated as a part of our ACF Database (n= 380). Results: The UIC Medical Center serves as a community hospital to an economically depressed adjacent population (median 1999 household income: $25,143 vs. US average $41,994). The average age of those screened was 58.6 ± 0.4 (mean ± SE), of whom 59.9% were female. The racial distribution was 57% African American, 17% Caucasian, and 12% Latino; with 25% covered by Public Aid or Medicaid. Overall, 12% had no ACF; 28% had 1-5 ACF, 20% had 5-9 ACF, and 40% had 10 or more ACF. ACF# increased with advancing age (r= 0.25, p<0.0001); was lower in patients without adenomatous polyps (10.7 ± 1.0) than those with 1 polyp (12.4 ± 1.8) or 2+ polyps (17.3 ± 2.4); and was higher in smokers (15.3 ± 2.0) than those who have never smoked (9.5 ± 1.2)(p= 0.03) as well as correlated with the amount smoked (i.e., pack-years; r= 0.17, p= 0.02). In contrast, there was no difference in ACF# between Caucasians (13.5 ± 2.6), African Americans (12.6 ± 1.1) or Latinos (9.7 ± 1.7). There also was no association for ACF# with body mass index, aspirin or multivitamin consumption. Of these patients, 178 also completed a 36-page NIH Dietary Recall Questionnaire, allowing for diet quantification using Diet*Calc Analysis (v.1.3.2, NCI Applied Research Program). Although no one dietary agent significantly correlated with ACF#, those with the strongest associations included calcifediol (r= -0.12, p= 0.10), fiber (r= -0.11, p= 0.13) and manganese (r= -0.11, p= 0.14). Intriguingly, persons with 10+ ACF consumed less theobromine than those with 10 ACF (p= 0.07). Conclusions: ACF# correlates with adenomatous polyp presence and number, as well as with smoking. Economically depressed populations may have higher ACF# independently of race. Selected dietary agents may protect against ACF formation.