Body iron stores and risk of colonic neoplasia

Body iron stores and dietary iron intake have both been shown to be positively associated with subsequent risk of colon cancer. This finding comes from a cohort study involving 14,000 men, but the positive association occurred in only 12 cases.

We performed a case-control study of 264 men and 98 women to test for an association between serum ferritin levels and the presence of adenoma of the colon that would be independent of other known risk factors.

Serum ferritin levels were determined in this study from sera, frozen at -80 degrees C for 5-8 years, that had been originally obtained between 1984-1987 at the Walter Reed Army Medical Center from adult male and postmenopausal female patients undergoing routine colonoscopic examination and previously enrolled in a case-control study that assessed the potential dietary and environmental risk factors for colonic neoplasia. The presence of fecal occult blood in the stool or the suggestion of colonic polyps seen on barium enema defined eligibility for the study. Patients with known preexisting colonic disease were excluded. Eligible patients had their blood drawn and serum prepared. Following colonoscopy and histologic review, the patients were classified into three groups: normal (without neoplastic disease), 159 subjects; adenoma, 145 subjects; and colon cancer, 29 subjects. Body iron stores were determined by measuring serum ferritin levels by a competitive-binding radiometric immunoassay. Ferritin levels categorized into quintiles for adenoma were defined. Crude and adjusted odds ratios (ORadj) with 95% confidence intervals (CIs) for cancer and adenoma related to ferritin were calculated, controlling for known or suspected risk factors including sex, age, race, body mass index, family history, tobacco use, and alcohol consumption.

Statistically significant associations of adenoma risk were seen in the third ([ORadj] = 3.8; 95% CI = 1.5-9.5) and fourth (ORadj = 5.1; 95% CI = 2.0-12.7) quintiles of ferritin relative to the first quintile, for smoking history (ORadj = 2.4; 95% CI = 1.3-4.3), for male sex (ORadj = 1.9; 95% CI = 1.0-3.7), and for family history of polyps or cancer (ORadj = 1.8; 95% CI = 1.0-3.4). From a second set of analyses that excluded 36 patients with serum ferritin of greater than or equal to 399 ng/mL, the greatest effect of ferritin on adenoma risk by anatomic subsite was seen in the right colon.

The apparent dose-response for serum ferritin level and adenoma risk suggest that exposure to iron may be related to adenoma formation.