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

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

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Oncology Health Sciences, Epidemiology
关键词	colorectal adenoma colorectal cancer MIB1 (Ki-67) cell proliferation
Committee Chair / Thesis Advisor	Bostick, Roberd M, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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