TGFβ₁ expression in normal-appearing rectal mucosa in individuals with and without sporadic colorectal adenomatous polyps.

A23

Introduction: TGFβ₁, 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 TGFβ₁ 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 TGFβ₁ 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. TGFβ₁ values were log transformed to improve normality, and analysis of covariance and graphical methods were used to compare overall mean levels and distributions of TGFβ₁ expression in the colorectal crypts between cases and controls. Results: The mean, overall expression level of TGFβ₁ in colon crypts did not substantially differ between cases and controls (p = 0.74). However, a graphical analysis revealed that the crypt distribution of TGFβ₁ 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. TGFβ₁ expression was 17% lower in persons who where obese (p = 0.01). Conclusions: These preliminary results suggest that, although the overall TGFβ₁ 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 TGFβ₁ expression may be associated with obesity, raising the possibility that weight reduction could modify TGFβ₁ and thus risk for colorectal neoplasms. Analyses of specimens from the remaining participants are underway.