Markers of the APC/beta-catenin signaling pathway as potential treatable, pre-neoplastic biomarkers of risk for colorectal neoplasms

Cancer Epidemiology, Biomarkers & Prevention, 05/11/2012

Ahearn TU et al. – These preliminary data suggest that the combined expression of APC and beta-catenin in the normal rectal mucosa may be associated with risk for incident, sporadic colorectal neoplasms, as well as with modifiable risk factors for colorectal neoplasms. Our results may help advance the development of treatable, pre-neoplastic biomarkers of risk for colorectal neoplasms

Methods

  • We evaluated APC, beta-catenin, and E-cadherin expression in normal mucosa from the rectum and ascending and sigmoid colon using automated immunohistochemistry and quantitative image analysis.
  • Diet, lifestyle, and medical history were assessed with validated questionnaires.

Results

  • In the normal rectal mucosa, the ratio of the proportion of APC expression in the upper 40% of crypts with total ?-catenin expression (APC/beta-catenin score) was 14.3% greater in controls than in cases (p=0.02) (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.14 - 1.14).
  • Compared to controls, in cases, APC expression was 3.2% lower, ?-catenin expression was 3.0% higher, and E-cadherin expression was 0.7% lower; however, none of these differences was statistically significant.
  • The APC/?-catenin score statistically significantly differed according to categories of plausible risk factors for colorectal cancer (e.g., it was 17.7% higher among those with 25[OH]-vitamin D3 concentrations >/= 27 ng/ml).

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