title: Iron in relation to gastric cancer in the Alpha-tocopherol, Beta-carotene Cancer Prevention Study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS/Suite 550/Room 5014, Bethesda, MD 20852-7234, USA. michael.cook@nih.gov
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wood
authors.forename: Gayle
authors.initials: G
authors.lastname: Petty
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004311:Double-Blind Method; D005293:Ferritins / Q000097:blood; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D014168:Transferrin / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage*; D019207:beta Carotene / Q000008:administration & dosage*
chemical_list: D010919:Placebos; D014168:Transferrin; D019207:beta Carotene; D005293:Ferritins; D007501:Iron; D024502:alpha-Tocopherol