Folic Acid in Preventing Colorectal Polyps in Patients With Previous Colorectal Polyps

The Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) Folic Acid Prevention Trial

RATIONALE: Chemoprevention is the use of certain substances to keep cancer from forming. The use of folic acid may prevent colorectal cancer.

PURPOSE: This randomized clinical trial is studying how well folic acid works compared with a placebo in preventing colorectal polyps in patients who have had previous colorectal polyps.

OBJECTIVES:

Primary

• Determine if folic acid supplementation lowers the adenoma recurrence rate.

Secondary

• Determine the number of adenomas per patient and the size and histology of the adenoma.
• Assess the interaction between folic acid and alcohol, methionine, and aspirin intake.
• Assess the interaction between folic acid and pretrial and midtrial folate levels.
• Assess other complementary biomarkers such as DNA methylation and blood folate level as risk factors for polyp recurrence.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral folic acid once daily.
• Arm II: Patients receive oral placebo once daily. At least 1 year after beginning treatment, patients are sent a blood collection kit in order to measure plasma vitamin B12 levels, to measure folate to assess compliance.

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Participated in the Nurses' Health Study (NHS I) or the Health Professionals Follow-Up Study (HPFS) and have had a previous confirmed diagnosis of adenomatous polyp of the colon or rectum
• Plan on having an endoscopy within 4 years after initiation of the trial
• Must release medical records regarding past and any future endoscopies

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Plasma vitamin B12 concentration of ≥ 300 pg/mL or have a vitamin B12 concentration between 200 and 299 pg/mL and a methylmalonic acid (MMA) level ≤ 32 µg/L

Exclusion criteria:

• Diagnosis of cancer other than non-melanoma skin cancer, or early stage breast or prostate cancer
• Diagnosis of homocystinemia
• Diagnosis of pernicious anemia
• Any gastrointestinal disorder that could lead to a vitamin B12 deficiency
• Diagnosis of cirrhosis or pancreatitis
• Diagnosis of epilepsy, Alzheimer's disease, Parkinsonism, and psychiatric disorders that may interfere with normal functioning

PRIOR CONCURRENT THERAPY:

Exclusion criteria:

• No prior gastrectomy, total colectomy, or pancreatectomy
• Other concurrent multivitamins or supplements that contain folic acid (they may take specific supplements, such as A, C, E, calcium, and iron, or antioxidant formula vitamins)
• No concurrent methotrexate or anticonvulsant