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)