Associations of Dietary, Lifestyle, and Other Participant Characteristics with APC, β-catenin, E-cadherin, and MSH2 Expression in the Normal Mucosa of Sporadic Colorectal Adenoma Patients Öffentlichkeit

Shu, Timothy (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/ws859g73z?locale=de
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Abstract

Abnormal expression of the Wnt pathway proteins APC, β-catenin, and E-cadherin, as well as of the DNA mismatch repair protein MSH2 is common during colorectal carcinogenesis. To investigate associations of selected demographic, lifestyle, dietary, and medical characteristics with the expression of these proteins in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, we measured APC, β-catenin, E-cadherin, and MSH2 colorectal crypt expression in biopsies of the normal-appearing colorectal mucosa from 104 participants using automated immunohistochemistry and quantitative image analysis. We used multivariable general linear models to compare mean biomarker expression across categories of participant characteristics. For those with the highest total meat consumption versus the lowest, the adjusted mean ratio of APC expression to β-catenin expression (APC/β-catenin) was 33% lower (p=0.03) in the whole crypt. For those with the highest vegetable and fruit consumption versus the lowest, mean E-cadherin expression was 29% higher (p=0.02) in the whole crypt. For those with the highest serum 25-OH vitamin D concentrations versus the lowest, the ratio of MSH2 expression to mib-1 expression (MSH2/mib-1 score) was 29% higher (p=0.03) in the whole crypt. These findings support that (i) lower total meat consumption, higher vegetable and fruit consumption, and higher vitamin D exposure may be favorably associated with the expression of biomarkers of risk for colorectal neoplasms in the normal-appearing colorectal mucosa, and (ii) further investigation into associations of demographic, lifestyle, dietary, and medical characteristics with biomarkers of risk for colorectal neoplasms is warranted.

Table of Contents

Introduction .............................................. 1

Materials and Methods .............................. 4

Results ...................................................... 10

Discussion ................................................ 18

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