Effect of Exercise on Biomarkers of Colon Cancer Risk

The specific aims of the proposed study are:

• To measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. a delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on proliferation rate in the upper part of colon and rectal mucosa crypts.
• To also measure the effects of a one-year moderate/vigorous intensity aerobic exercise program vs. delayed-exercise control program in persons that have undergone a colonoscopy within the past 36 months on:

• expression of apoptosis-related proteins (bax/bcl-2 ratio) in colon and rectal mucosal biopsies
• rectal mucosal prostaglandin levels
• fasting serum/plasma insulin, glucose, triglycerides, insulin-like growth factor 1(IGF-1), and IGF binding protein-3 (IGFPB-3)
• body fat mass and distribution (body mass index, waist and hip circumferences, bioelectrical impedance, DEXA scan)
• subcutaneous abdominal and intra-abdominal fat mass (measured by one-slice CT scan at the L4 level)
• fitness (VO2max)
• quality of life (measured by standardized self-report instruments)
• sleep quality

Inclusion criteria

• Male or female
• Completed a colonoscopy within the past 36 months
• Ages 40-75 years at time of identification
• Sedentary activity pattern
• Gives informed consent, agrees to be randomly assigned
• Able to perform all study requirements, able to follow directions and complete forms

Exclusion criteria

• Colorectal cancer at any time; any other invasive cancer within the past 10 years (simple basal or squamous cell carcinoma okay)
• Plans to leave Western Washington during the follow-up period
• Morbidly obese (BMI > 41), weight loss of > 10 pounds in the previous 3 months
• Familial polyposis, Gardner's syndrome, or other known familial colorectal cancer syndrome
• Ulcerative colitis or short bowel
• "Excessive"(> 3 x week) laxative or enema use that might interfere with rectal crypt studies
• Current use of certain medications likely to interfere with success of the intervention, or with outcomes measures (for example, anticoagulants because of risk from colorectal biopsy, diet medications within past 6 months)
• Diabetes mellitus or fasting glucose > 140
• Hemochromatosis- if diagnosed by physician
• Abnormal screening labs (hematocrit < 32 or > 48, white blood cells < 3.0 or > 15.0, potassium < 3.5 or > 5.3, fasting glucose > 140, creatinine > 2.0), or abnormalities on screening physical exam judged by study physicians to contraindicate participation in an exercise program
• Contraindications for entry into a training program 131 including: unstable angina, uncontrolled hypertension (systolic > 200, diastolic > 100), orthostatic hypotension (>20 mm fall in systolic), moderate/severe aortic stenosis, uncontrolled arrhythmia, uncontrolled congestive heart failure, third degree heart block, pericarditis, myocarditis, pulmonary/systemic embolism within the past 6 months, thrombophlebitis, ST displacement > 3 mm at rest, history of cardiac arrest)
• Contraindications for exercise testing 131 including: recent (within 6 months) cardiac event (MI, pulmonary edema, myocarditis, pericarditis), unstable angina, uncontrolled arrhythmia, third degree heart block, left bundle branch block, acute congestive failure, recent (within 6 months) pulmonary/systemic embolus, severe electrolyte abnormality
• Meets criteria to stop screening exercise test 131 as decided by overseeing physician
• Volunteering in order to lose weight; alcohol or drug abuse, significant mental or emotional problems such as would interfere with compliance (as assessed by study staff impression)