Effect of Folate on DNA in Colon Tissue and Blood Samples From Patients at Increased Risk of Developing Colorectal Neoplasia

DISEASE CHARACTERISTICS:

• At increased risk for developing colorectal neoplasia due to 1 of the following:

  • Personal history of colorectal adenomatous polyps
  • Family history of colorectal adenoma or adenocarcinoma
• No hereditary nonpolyposis colorectal cancer (HNPCC)
• No more than one first-degree family member with colorectal or endometrial malignancies

PATIENT CHARACTERISTICS:

• Ambulatory
• Female patients must be ≥ 2 years post-menopausal (i.e., 2 years after the last menstrual period)
• Negative pregnancy test
• Male patients must use effective contraception during and for 2 months after completion of study treatment (for male patients enrolled in the folate depletion group)
• Serum folate level ≤ 20 ng/mL
• Plasma vitamin B12 level ≥ 250 pg/mL
• Serum homocysteine level ≤ 17 μmol/L
• ALT or AST ≤ 2 times upper limit of normal
• No unexplained elevated alkaline phosphatase
• Creatinine ≤ 2.0 mg/dL
• HIV negative
• No folate metabolism abnormalities or predisposing conditions
• No prior malignancy except nonmelanoma skin cancer
• No intestinal malabsorption or inflammatory bowel disease
• No excessive bleeding or coagulation disorder
• No untreated hyperthyroidism
• No diabetes mellitus requiring insulin
• No daily alcohol intake > 2 ½ shot glasses of whisky or three 8-ounce glasses of beer or wine
• No sustained blood pressure > 150/95 mm Hg for three consecutive readings
• No other serious illness that would limit life expectancy to < 6 months

PRIOR CONCURRENT THERAPY:

• No prior gastrointestinal surgery, including gastrectomy or small or large bowel resections

  • Prior appendectomy or surgery of the esophagus allowed

• More than 3 months since regular ingestion of ≥ 650 mg of aspirin (≥ 2 tablets of 325 mg regular strength OR > 1 tablet of 500 mg extra strength aspirin) per day

  • The following drugs are allowed for cardiovascular prophylaxis provided the patient has been taking the drug regularly for ≥ 1 month and continues to take the same dose during study participation:

    • One or two regular strength aspirin tablets (i.e., 325 mg per tablet) per day
    • One baby aspirin tablet (81 mg tablet) per day
• More than 3 months since regular daily ingestion of other non-steroidal anti-inflammatory drugs (NSAIDs)
• No concurrent anticoagulation therapy
• No concurrent sterol-binding resins, such as cholestyramine (for the treatment of high blood cholesterol)
• No other concurrent investigational drugs
• No other concurrent medications that might, in the view of the study physicians, alter rectal mucosal proliferation, folate metabolism, or renal/hepatic metabolism
• No concurrent weight control medications
• No concurrent supplemental folate preparation containing > 400 mcg of folic acid per day

• No concurrent hormone replacement therapy, including oral, transplanted, or injected contraceptives

  • Concurrent thyroid hormone replacement allowed provided the patient is euthyroid

• No concurrent medication interfering with folic acid metabolic effects, including any of the following:

  • Methotrexate
  • Phenytoin
  • Phenobarbital
  • Primidone
  • Sulfonamides
  • Folinic acid derivatives

• No concurrent lipid-lowering medications other than usual doses of the class of drugs known as statins

  • The following statin drugs are allowed provided the patient has been taking the drug regularly for ≥ 1 month and continues to take the same dose during study participation:

    • Atorvastatin (10 or 20 mg/day)
    • Fluvastatin (20 mg or 40 mg/day)
    • Lovastatin (10 or 20 mg/day)
    • Pravastatin (10 or 20 mg/day)
    • Simvastatin (5 or 10 mg/day)