title: Systemic and tumor level iron regulation in men with colorectal cancer: a case control study.
abstract: BACKGROUND
  Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC.
  
  
  METHODS
  The participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls' iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained.
  
  
  RESULTS
  Cases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 μg/mL, p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ(2) = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0 ng/mL, p < 0.05).
  
  
  CONCLUSIONS
  While CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611, USA.
authors.forename: Cenk K
authors.initials: CK
authors.lastname: Pusatcioglu
authors.affiliation: Department of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor St, Chicago, IL 60612, USA.
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
authors.affiliation: Section of Digestive Disease and Nutrition, University of Illinois at Chicago, 840 S Wood St, Chicago, IL 60612, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.affiliation: Division of Epidemiology and Biostatistics, University of Illinois at Chicago, 1603 W Taylor St, Chicago, IL 60612, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Freels
authors.affiliation: Department of Medicine, University of Illinois at Chicago, 1747 W Roosevelt Rd, Chicago, IL 60608, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Tussing-Humphreys
authors.affiliation: Department of Pathology, University of Illinois at Chicago, 840 S Wood St, Chicago, IL 60612, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cabay
authors.affiliation: Department of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.
authors.forename: Rose
authors.initials: R
authors.lastname: Linzmeier
authors.affiliation: Department of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.
authors.forename: Damond
authors.initials: D
authors.lastname: Ng
authors.affiliation: Section of Digestive Disease and Nutrition, University of Illinois at Chicago, 840 S Wood St, Chicago, IL 60612, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Clark
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 W Taylor St, Chicago, IL 60612, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Braunschweig
keywords: Anemia; Colorectal cancer; Hepcidin; Inflammation; Iron metabolism