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

This is an interventional prevention trial for Colorectal Cancer focused on measuring colon cancer, rectal cancer Read More

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)