Iron in Relation to Gastric Cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Background: Iron is an essential micronutrient that can have carcinogenic effects when at high or low concentrations. Previous studies of iron in relation to gastric cancer have not assessed subtype-specific relationships. We used the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to assess whether iron metrics were associated with gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Methods: We selected 341 incident gastric cancer cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of follow-up, and 341 individually matched controls. We measured prediagnostic serum iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total iron-binding capacity (TIBC) and transferrin saturation were estimated from these metrics. Dietary iron exposures were estimated from a food frequency questionnaire. Multivariable logistic regression was used for analysis. Results: Serum iron metrics were not associated with GCC, except for a potential "n"-shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and, possibly, transferrin saturation. TIBC appeared to share a "u"-shaped relationship with GNCC (global P = 0.033). Dietary iron exposures were not associated with either subsite. Adjustment for Helicobacter pylori and gastric atrophy had little effect on observed associations. Conclusions: We found little evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC was associated with an iron profile similar to that of iron deficiency. Impact: Our findings indicate that inverse associations between iron metrics and gastric cancer are driven by associations with GNCC. Further elucidation of potential mechanisms is warranted. Cancer Epidemiol Biomarkers Prev; 21(11); 2033-42. (C)2012 AACR.