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Risk Factors for Colorectal Cancer in Relation to Number and Size of Aberrant Crypt Foci in Humans

¹ Veterans Affairs Puget Sound Health Care System; ² Cancer Prevention Program, Fred Hutchinson Cancer Research Center; Departments of ³ Medicine, ⁴ Epidemiology, and ⁵ Pathobiology, University of Washington, Seattle, Washington; and ⁶ Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio

Requests for reprints: Rebecca E. Rudolph, Fred Hutchinson Cancer Research Center, P.O. Box 19024, M3-B232, Seattle, WA 98109-1024. Phone: 206-667-4678; Fax: 206-667-5977. E-mail: rrudolph{at}fhcrc.org

Several characteristics of aberrant crypt foci (ACF) suggest that they are precursors of colorectal cancer, but the factors that promote or inhibit their growth are largely unknown. We conducted a pilot study to explore whether factors associated with risk of colorectal cancer are also associated with number or size of rectal ACF. Thirty-two U.S. veterans, ages 50 to 80 years, were recruited to undergo magnifying chromoendoscopy for imaging of rectal ACF and colonoscopy for identification of polyps or cancer. Participants completed a questionnaire on cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and family history of colorectal cancer. Fisher's exact test was used to assess the statistical significance of associations between colorectal cancer risk factors and characteristics of ACF. Cochran-Mantel-Haenszel statistics and polytomous regression were used to test the significance of associations adjusted for age. Participants with a history of adenoma had more ACF than those without (age-adjusted P = 0.02), but the numbers in the two groups overlapped markedly. Older participants had more (P = 0.06) and larger (P = 0.009) ACF than younger participants. No associations were identified between either ACF number or size and cigarette smoking, use of NSAIDs, or family history of colorectal cancer. These findings suggest that persons with adenomas have somewhat more rectal ACF than persons without, and that older age is a risk factor for ACF growth. Future research should be directed toward developing techniques to identify ACF that are likely to progress to cancer and the modifiable factors that promote or inhibit such progression.

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