Despite effective use of screening colonoscopy, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths. ‘Interval’ cancers, or those occurring between screening colonoscopy procedures, are often found within the proximal (right) colon, underscoring the need for advanced screening approaches using high-definition chromoendoscopy. To better define the colonic mucosa at-risk, we have focused considerable effort on identification and molecular analysis of aberrant crypt foci (ACF), an early macroscopically detectable lesion commonly found in the distal colon. ACF may serve as a surrogate marker of cancer risk, but have rarely been studied within context of the right colon. We hypothesize that proximal ACF may associate with risk factors for CRC and act as a surrogate marker for CRC risk. While distal ACF are frequent (approximately 13 per patient) proximal ACF are not (<1 per patient). We report that subjects with at least one proximal ACF are significantly more likely to have higher ACF multiplicity (p = 0.0002) and more importantly, are more likely to harbor synchronous colonic neoplasia (OR=2.38 [1.24-4.59], p = 0.0087). Histologically, proximal ACF are more frequently dysplastic (41%) compared to distal colon ACF (8%). ACF (n=49) were analyzed for a panel of oncogenes and tumor suppressors using mass spectrometry (MS)-based genotyping (Sequenom). Among the 112 targets analyzed, after KRAS (20%) and BRAF (22%), APC mutations (12%) were most common and specifically associated with dysplasia. Due to their diminutive size and flat morphology, proximal ACF are almost certainly missed during routine colonoscopy. However, our findings suggest that the identification, removal and analysis of proximal ACF may be especially important during screening colonoscopy of high-risk individuals.

Citation Format: David A. Drew, Matthew P. Hanley, Allen Mo, Gyuhyeong Goh, Nicole A. Horelik, Thomas J. Devers, Joel Levine, Richard G. Stevens, James J. Grady, Daniel W. Rosenberg. Proximal human aberrant crypt foci as surrogate markers of colorectal cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3240. doi:10.1158/1538-7445.AM2014-3240