Grant Number:	5R01CA077572-05 Interpret this number
Primary Investigator:	Mctiernan, Anne
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Exercise Intervention in Colorectal Polyp Patients
Fiscal Year:	2004

DESCRIPTION (Adapted from the Applicant's Abstract): Strong observational evidence points to a link between physical activity and reduction in risk of colon cancer. The mechanisms for this association have not been delineated, nor have the amounts and types of exercise needed for a putative protective effect been determined. We propose a randomized controlled clinical trial of a one-year moderate aerobic/strength training exercise intervention in adenomatous colon polyp patients (n=100 men, 100 women). We hypothesize that polyp patients in an exercise intervention will experience significant biological effects on colorectal epithelium, specifically Ki67 indices of proliferation, bax and bc1-2 markers of apoptosis, and prostaglandin concentrations (PGE2 and PGF2cc). Patients will be recruited on-site from gastroenterology physicians' offices and secondarily from a high-risk colorectal cancer family registry. Sedentary individuals with newly diagnosed (within the past 18 months) adenomatous colon polyp(s) will be screened for eligibility and randomized to either the exercise intervention or a stretching-control group. The exercise intervention will use existing proven methods for adopting and maintaining exercise, taken from our ongoing research program. It will consist of 3 months' facility-based exercise instruction in small groups, followed by 9 months' home-based exercise program supplemented with group behavior change meetings. The goal for exercise will be moderate-level aerobic exercise 5-6 days per week for 30-45 minutes, plus strength training 2 days per week for 15-20 minutes. Colon and rectal biopsies will be taken at baseline and 12-months, and examined for amount and patterns of epithelial cell proliferation (with Ki67 marker) and apoptosis markers (bc1-2 and bax, an inhibitor and an inducer of apoptosis, respectively). Additional potential markers of exercise effect on colon cancer risk will be measured, including rectal mucosal biopsy prostaglandin concentrations, stool frequency, insulin-like growth factor (IGF-1) and IGF binding protein (IGFBP-3), insulin, glucose, C-peptide, triglycerides, and measures of fat mass and fat distribution. Other measures at baseline and 12 months include fitness (V02max), self-reported physical activity, diet, and quality of life. Results from this unique human experimental study will provide important information about mechanisms of exercise effects on colon carcinogenesis and about potential




Exercise effects on DNA methylation in EVL, CDKN2A (p14, ARF), and ESR1 in colon tissue from healthy men and women.
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PMID: 34550860
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Predicting adherence of adults to a 12-month exercise intervention.
Authors: Cadmus-Bertram L. , Irwin M. , Alfano C. , Campbell K. , Duggan C. , Foster-Schubert K. , Wang C.Y. , McTiernan A. .
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EPub date: 2013-10-31.
PMID: 24176780
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Effects of physical activity on melatonin levels in previously sedentary men and women.
Authors: Thrift A.P. , Xiao L. , Patel S.R. , Tworoger S.S. , McTiernan A. , Duggan C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Aug; 23(8), p. 1696-9.
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Authors: Imayama I. , Alfano C.M. , Mason C.E. , Wang C. , Xiao L. , Duggan C. , Campbell K.L. , Foster-Schubert K.E. , Wang C.Y. , McTiernan A. .
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Injuries in sedentary individuals enrolled in a 12-month, randomized, controlled, exercise trial.
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A 12-month moderate-intensity exercise intervention does not alter serum prolactin concentrations.
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Authors: Imayama I. , Alfano C.M. , Cadmus Bertram L.A. , Wang C. , Xiao L. , Duggan C. , Campbell K.L. , Foster-Schubert K.E. , McTiernan A. .
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A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk.
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No reduction in C-reactive protein following a 12-month randomized controlled trial of exercise in men and women.
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No effect of exercise on colon mucosal prostaglandin concentrations: a 12-month randomized controlled trial.
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Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Nov; 16(11), p. 2351-6.
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Effect of a 12-month exercise intervention on the apoptotic regulating proteins Bax and Bcl-2 in colon crypts: a randomized controlled trial.
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