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Biomarkers and Early Detection: Risk Markers and Surrogate Endpoints

TGFß₁ expression in normal-appearing rectal mucosa in individuals with and without sporadic colorectal adenomatous polyps.

Emory University, Atlanta, GA

Abstract

A23

Introduction: TGFß₁, an autocrine/paracrine growth factor that inhibits cell growth and proliferation, may be an important modulator of an individual's risk of colorectal cancer. We hypothesized that TGFß₁ expression in normal-appearing rectal mucosa is lower in persons with sporadic adenomas than in those without, and may serve as a treatable biomarker of risk of colorectal neoplasms. Methods: We conducted a colonoscopy-based case-control study comprised of 49 cases and 152 controls. We measured TGFß₁ expression in biopsies of normal-appearing rectal mucosa in a randomly selected subset of 28 cases and 37 controls using automated immunohistochemical methods and quantitative image analysis software. TGFß₁ values were log transformed to improve normality, and analysis of covariance and graphical methods were used to compare overall mean levels and distributions of TGFß₁ expression in the colorectal crypts between cases and controls. Results: The mean, overall expression level of TGFß₁ in colon crypts did not substantially differ between cases and controls (p = 0.74). However, a graphical analysis revealed that the crypt distribution of TGFß₁ differed between cases and controls, with expression in the upper 40% of the crypt (the non-proliferative zone) higher in cases than in controls, and expression in the lower 60% of the crypt (the proliferative zone) higher in controls than in cases. TGFß₁ expression was 17% lower in persons who where obese (p = 0.01). Conclusions: These preliminary results suggest that, although the overall TGFß₁ expression in normal-appearing rectal tissue may not substantially differ between persons at higher or lower risk for colorectal neoplasms, there may be a shift in the distribution of the expression in the crypts with increased risk. The results also suggest that colon crypt TGFß₁ expression may be associated with obesity, raising the possibility that weight reduction could modify TGFß₁ and thus risk for colorectal neoplasms. Analyses of specimens from the remaining participants are underway.