Effects of Ginger Supplementation on Cell-Cycle Biomarkers in the Normal-Appearing Colonic Mucosa of Patients at Increased Risk for Colorectal Cancer: Results from a Pilot, Randomized, and Controlled Trial

• Authors: Jessica Citronberg, Emory University; Roberd Bostick, Emory University; Thomas Ahearn, Emory University; D. Kim Turgeon, University of Michigan; Mack T. Ruffin, University of Michigan; Zora Djuric, University of Michigan; Ananda Sen, University of Michigan; Dean E. Brenner, University of Michigan; Suzanna M. Zick, University of Michigan
• Journal Title: Cancer Prevention Research
• Volume: Volume 6, Number 4
• Publisher: American Association for Cancer Research | 2013-04-01, Pages 271-281
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1940-6207.CAPR-12-0327
• Subjects: Health Sciences, Oncology; Health Sciences, Epidemiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; ZINGIBER-OFFICINALE ROSCOE; CONTROLLED CLINICAL-TRIAL; ANGIOGENESIS IN-VITRO; PROLIFERATIVE ACTIVITY; ADENOMATOUS POLYPS; HL-60 CELLS; DNA-DAMAGE; MOUSE SKIN; VITAMIN-D; APOPTOSIS

Abstract

To estimate the effects of ginger on apoptosis, proliferation, and differentiation in the normal-appearing colonic mucosa, we randomized 20 people at increased risk for colorectal cancer to 2.0 g of ginger or placebo daily for 28 days in a pilot trial. Overall expression and distributions of Bax, Bcl-2, p21, hTERT, and MIB-1 (Ki-67) in colorectal crypts in rectal mucosa biopsies were measured using automated immunohistochemistry and quantitative image analysis. Relative to placebo, Bax expression in the ginger group decreased 15.6% (P = 0.78) in the whole crypts, 6.6% (P = 0.95) in the upper 40% (differentiation zone) of crypts, and 21.7% (P = 0.67) in the lower 60% (proliferative zone) of crypts; however, there was a 19% increase (P = 0.14) in Bax expression in the upper 40% relative to the whole crypt. While p21 and Bcl-2 expression remained relatively unchanged, hTERT expression in the whole crypts decreased by 41.2% (P = 0.05); the estimated treatment effect on hTERT expression was larger in the upper 40% of crypts (-47.9%; P = 0.04). In the ginger group, MIB-1 expression decreased in the whole crypts, 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. These pilot study results suggest that ginger may reduce proliferation in the normal-appearing colorectal epithelium and increase apoptosis and differentiation relative to proliferation-especially in the differentiation zone of the crypts and support a larger study to further investigate these results.