folate-depleted diet compared with folate-supplemented diet in preventing colorectal cancer in patients at high risk for colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: chemoprevention therapy is the use of certain agents to try to prevent the development of cancer. the use of folic acid may be effective in preventing colorectal cancer. eating a diet rich in folic acid may prevent the development of colorectal cancer. purpose: this randomized phase i trial is studying how well a folate-depleted diet works compared to a folate-supplemented diet in preventing colorectal cancer in patients who are at high risk for developing colorectal cancer.

objectives: primary * analyze the effects of a folate-depleted vs a folate-supplemented diet on folate-related dna endpoints (e.g., genomic and gene-specific dna methylation and dna strand breaks) in rectal epithelial cells in patients at high risk for colorectal neoplasia. * analyze the effects of these dietary interventions on folate-related dna endpoints (e.g., genomic and gene-specific dna methylation, dna strand breaks, and uracil incorporation into dna) in blood mononuclear cells in these patients. secondary * analyze the effects of these dietary interventions on the patterns of differential gene expression in rectal epithelial cells and blood mononuclear cells in these patients. outline: this is a randomized, single-blind study. * run-in period: patients are placed on an average folate-containing diet for 56 days. * randomization: after completion of the run-in period, patients are randomized to 1 of 2 arms. * arm i (folate depleted diet): patients are placed on a low-folate diet for 84 days. patients receive oral folic acid supplementation once daily on days 57-84. * arm ii (folate supplemented diet): patients continue on an average folate-containing diet for an additional 56 days. patients receive oral folic acid supplementation once daily on days 1-56. patients are followed at 4 weeks. projected accrual: a total of 20 patients (10 per arm) will be accrued for this study within 2.5 years.

Eligibility criteria:
disease characteristics: * healthy persons at increased risk for colorectal neoplasia due to 1 of the following reasons: * personal history of colorectal adenomatous polyps * family history of colorectal adenoma or adenocarcinoma * no history of multiple family members with colorectal neoplasia that is suggestive of dominant hereditary neoplasia patient characteristics: age * 40 to 72 performance status * ambulatory life expectancy * at least 6 months hematopoietic * no excessive bleeding or coagulation disorder hepatic * alt or ast ≤ 2 times upper limit of normal * no unexplained elevated alkaline phosphatase renal * creatinine ≤ 2.0 mg/dl cardiovascular * homocysteine concentration ≤ 17um/l * no sustained blood pressure \> 150/95 mm hg for 3 consecutive readings other * vitamin b_12 ≥ 250 pg/ml * folate level ≤ 20 mg/dl * hiv negative * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 4 weeks after study participation * no intestinal malabsorption or inflammatory bowel disease * no prior malignancy except nonmelanoma skin cancer * no calcium metabolism abnormalities or predisposing conditions, such as hyperparathyroidism * no untreated hyperthyroidism * no untreated insulin-requiring diabetes mellitus * no daily alcohol intake \> 2 ½ shot glasses of whiskey or three 8 ounce glasses of beer or wine * no other serious illness that might limit life expectancy to \< 6 months prior concurrent therapy: biologic therapy * none chemotherapy * none endocrine therapy * no concurrent hormone replacement therapy, including oral, transplanted, or injected contraceptives * concurrent thyroid hormone replacement is allowed as long as the patient is euthyroid for 3 months radiotherapy * none surgery * no prior gastrointestinal surgery, including gastrectomy or small or large bowel resections * prior appendectomy or surgery of the esophagus allowed other * more than 3 months since regular ingestion of ≥ 650 mg per day of aspirin (≥ 2 tablets of 325 mg regular strength or \> 1 tablet of 500 mg extra strength aspirin) * more than 3 months since regular daily ingestion of nonsteroidal anti-inflammatory drugs * at least 1 month since vitamin, mineral, or herbal supplementation * no other concurrent vitamin, mineral, or herbal supplementation * no concurrent anticoagulants * no concurrent sterol-binding resins (i.e., cholestyramine) * no other concurrent investigational drugs or medications that might alter rectal mucosal proliferation, folate metabolism, or renal/hepatic impairment * no concurrent weight control medications * no concurrent supplemental folate preparations containing \> 400 mcg of folic acid per day * no concurrent lipid-lowering medications * the following concurrent statin drugs are allowed provided patient has been taking a stable dose for ≥ 1 month: * atorvastatin 10 or 20 mg/day * fluvastatin 20 or 40 mg/day * lovastatin 10 or 20 mg/day * pravastatin 10 or 20 mg/day * simvastatin 5 or 10 mg/day

Keywords: colon cancer rectal cancer