Colorectal Epithelial Cell Proliferation and Risk for Incident, Sporadic Colorectal Adenomatous Polyps Open Access

Chen, Dan (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/db78tc256?locale=en
Published

Abstract

Background: It is hypothesized that colorectal epithelial cell proliferation kinetics are altered in the normal mucosa of patients at increased risk for colon cancer, the second leading cause of cancer deaths in the United States; however, there are no reports of well-conducted observational epidemiologic studies that have investigated this hypothesis.

Objective: To assess whether colorectal epithelial cell proliferation in the normal-appearing colorectal mucosa may be a valid, potentially modifiable biomarker of risk for colorectal neoplasms.

Methods: We conducted a pilot, colonoscopy-based case-control study (30 cases, 50 controls) of incident, sporadic colorectal adenoma. Cell proliferation was measured using immunohistochemistry for MIB1 (epitope of Ki-67). The labeling index (LI), the indicator of overall proliferation, was calculated as the proportion of labeled cells in the crypt; an LIb40 and LIt40 were also calculated to indicate the degree of proliferation in the upper 40% of the crypts (differentiation zone) and the lower 60% of the crypts (proliferative zone), respectively. A distributional index (Φh) to indicate expansion of the proliferative zone into the differentiation zone was calculated as the proportion of labeled cells in the crypts that were in the upper 40% of the crypts. Cases and controls were compared using analysis of covariance and logistic regression.

Results: In the adenoma cases relative to the controls, the LI, LIb60, LIt40, and Φh were proportionately lower by 17% (p = 0.03), 17% (p = 0.02), 28% (p = 0.08) and 28% (p = 0.33), respectively; the corresponding crude odds ratios (OR) and 95% confidence intervals were 0.39 (0.15, 1.05), 0.50 (0.19, 1.31), 0.62 (0.25, 1.54), and 0.88 (0.35, 2.17). The inverse associations tended to be stronger with adjustment for other risk factors, such as calcium and total fat intakes. The Φh was 36% higher (p = 0.05) among those with total calcium consumption above the mean.

Conclusion: Opposite to our hypotheses, these preliminary data suggest that lower cell proliferation as indicated by MIB1 expression in the normal colonic mucosa may be associated with increased risk of incident, sporadic colorectal adenoma as well as with modifiable risk factors thought to decrease risk for colorectal neoplasms.

Table of Contents

Tabel of Contents

Illustration

List of Tables

Chapter I. Literature Review............................................................................ 1

1... Colorectal Cancer and Descriptive Epidemiology................................................. 2

2... Molecular Basis of Colon Carcinogenesis........................................................... 2

3... Risk Factors for Colorectal Neoplasms.............................................................. 4

4... Colorectal Adenomatous Polyps..................................................................... 12

5... Role of Cell proliferation in the Development of Colorectal Adenoma...................... 12

6... Biomarkers of Risk for Colorectal Neoplasms..................................................... 13

Hypothesis................................................................................................... 15

Chapter II. Manuscript................................................................................... 16

Abstract........................................................................................................ 17

1... Introduction.............................................................................................. 19

2... Methods................................................................................................... 20

3... Resault..................................................................................................... 26

4... Discussion................................................................................................. 28

Chapter III. Summary, and Possible Future Directions...................................... 33

Reference..................................................................................................... 44

Appendix...................................................................................................... 60


About this Master's Thesis

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
School
Department
Subfield / Discipline
Degree
Submission
Language
  • English
Research field
Keyword
Committee Chair / Thesis Advisor
Partnering Agencies
Last modified

Primary PDF

Supplemental Files