ISPO

Published in Cancer Detection and Prevention 2004; 28(2):107-113.

Effects of low dose aspirin (81 mg) on proliferating cell nuclear antigen and Amaranthus caudatus labeling in normal-risk and high-risk human subjects for colorectal cancer

Koyamangalath Krishnan, MD, FRCPa, Toshihiro Aoki, MDb, Mack T. Ruffin, MD, MPHc, Daniel P. Normolle, PhDd, C. Richard Boland, MDb, Dean E. Brenner, MDe

aMedical Service, James H. Quillen Veterans Administration Medical Center and Division of Hematology­Oncology, Department of Internal Medicine, East Tennessee State University, Johnson City, TN 37614, USA bDivision of Gastroenterology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA cDepartment of Family Medicine, University of Michigan School of Medicine and Ann Arbor VA Medical Center, Ann Arbor, MI 48109, USA dDepartment of Comprehensive Cancer Center Biostatistics Unit, University of Michigan School of Medicine and Ann Arbor VA Medical Center, Ann Arbor, MI 48109, USA eDepartment of Internal Medicine, University of Michigan School of Medicine and Ann Arbor VA Medical Center, Ann Arbor, MI 48109, USA

Epidemiological, experimental, and clinical observations provide support for a colorectal cancer chemopreventive role for aspirin. We have evaluated the effects of aspirin on proliferation biomarkers in normal-risk and high-risk human subjects for colorectal cancer. Colorectal biopsies were obtained at baseline and at 24 h after 28 daily doses of 81 mg of aspirin from 13 high-risk and 15 normal-risk subjects for colorectal cancer. We evaluated aspirin's effects on proliferating cell nuclear antigen (PCNA) immunohistochemistry and epithelial mucin histochemistry using the lectin, Amaranthus caudatus agglutinin (ACA) in crypt sections from rectal biopsies. The baseline whole crypt PCNA LIs differed significantly between normal-risk and high-risk subjects. PCNA LIs are not affected by 28 days of aspirin at 81 mg daily. ACA LIs are decreased by 28 days of aspirin at 81 mg daily in both normal-risk and high-risk subjects. Aspirin's effects on ACA LIs may have mechanistic and biological implications that deserve further attention. PCNA and ACA LIs are not useful as proliferation biomarkers for aspirin's chemopreventive activity in morphologically normal human colorectal mucosa.

KEY WORDS: Aspirin, Colon cancer chemoprevention, Proliferation markers.

http://www.cancerprev.org/Journal/Issues/28/2/4868