Inclusion Criteria

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)