Effects of Ginger Supplementation on Markers of Apoptosis, Proliferation, and Differentiation in the Normal-Appearing Colonic Mucosa of Patients at High Risk for Colorectal Cancer: Results from a Pilot, Randomized, Controlled Trial Public

Abstract

Background: To estimate the effects of ginger on apoptosis, proliferation, and
differentiation in the normal human colorectal mucosa, we measured the expression of cell
cycle markers in the normal-appearing colon mucosa of patients at increased for CRC in a
pilot, randomized, double-blinded, placebo-controlled, clinical trial.

Methods: A total of 20 patients were treated with either 2.0 g (eight 250 mg capsules) of
encapsulated ginger (standardized to 5%-gingerols) or placebo daily for 28 days. Overall
expression and distributions of Bax, Bcl-2, p21, hTERT and MIB-1 in colorectal crypts in
biopsies of normal-appearing colon mucosa were detected and measured using automated
immunohistochemistry and quantitative image analysis. Percent changes in biomarker
expression over the treatment period were calculated, categorized, assigned a score and then
summed to construct a "cell-cycle score."

Results: Image analysis measurement intra-rater reliability was ≥ 0.90 for all biomarkers. In
the ginger group relative to the placebo group, Bax expression decreased 15.6% (p = 0.81)
along the full length of the crypts, 6.6% (p = 0.38) in the upper 40% (differentiation zone) of
the crypts, and 21.7% (p = 0.77) in the lower 60% (proliferative zone) of the crypts;
however, there was a 19% increase (p = 0.80) in the proportion of the expression of Bax in
the upper 40% relative to the whole crypt. While p21 and Bcl-2 expression remained
relatively unchanged, hTERT expression along the full length of crypts decreased by 41.2%
(p = 0.05); the estimated treatment effect on hTERT expression was slightly more
pronounced in the canonical differentiation zone of crypts (-47.9%; p = 0.04). In the ginger
group relative to the placebo group, MIB-1 expression decreased along the entire crypt,
upper 40% of crypts, and lower 60% of crypts by 16.9% (p = 0.39), 46.8% (p = 0.39), and
15.3% (p = 0.41), respectively.

Conclusions: These preliminary results 1) suggest that ginger may reduce proliferation in the
normal-appearing colorectal epithelium and increase apoptosis and differentiation relative to
proliferation-especially in the proliferative zone of the crypts, and 2) support a full-scale
clinical trial to further investigate these results.

Table of Contents

BACKGROUND ................................................................................................................................ 1
INTRODUCTION ............................................................................................................................. 8
METHODS ........................................................................................................................................ 10
RESULTS ............................................................................................................................................ 17
DISCUSSION .................................................................................................................................... 19
TABLES AND FIGURES ............................................................................................................... 25
CONCLUSIONS AND PUBLIC HEALTH IMPLICATIONS .............................................. 33
REFERENCES .................................................................................................................................. 35
APPENDICES ................................................................................................................................... 48

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Mot-clé	MIB-1 (Ki-67) Chemoprevention Ginger Bax Bcl-2 hTerT p21 Colorectal cancer Biomarkers of risk
Committee Chair / Thesis Advisor	Bostick, Roberd M, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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