title: Decreased cardiovascular and extrahepatic cancer-related mortality in treated patients with mild HFE hemochromatosis.
abstract: OBJECTIVE
  Mortality studies in patients with hemochromatosis give conflicting results especially with respect to extrahepatic causes of death. Our objective was to assess mortality and causes of death in a cohort of patients homozygous for the C282Y mutation in the HFE gene, diagnosed since the availability of HFE testing.
  
  
  METHODS
  We studied 1085 C282Y homozygotes, consecutively diagnosed from 1996 to 2009, and treated according to current recommendations. Mortality and causes of death were obtained from death certificates and compared to those of the general population. Standardized mortality ratios (SMRs) were used to assess specific causes of death and the Cox model was used to identify prognostic factors for death.
  
  
  RESULTS
  Patients were followed for 8.3±3.9 years. Overall the SMR was the same as in the general population (0.94 CI: 0.71-1.22). Patients with serum ferritin⩾2000 μg/L had increased liver-related deaths (SMR: 23.9 CI: 13.9-38.2), especially due to hepatic cancer (SMR: 49.1 CI: 24.5-87.9). Patients with serum ferritin between normal and 1000 μg/L had a lower mortality than the general population (SMR: 0.27 CI: 0.1-0.5), due to a decreased mortality, related to reduced cardiovascular events and extrahepatic cancers in the absence of increased liver-related mortality. Age, diabetes, alcohol consumption, and hepatic fibrosis were independent prognostic factors of death.
  
  
  CONCLUSIONS
  In treated HFE hemochromatosis, only patients with serum ferritin higher than 2000 μg/L have an increased mortality, mainly related to liver diseases. Those with mild iron burden have a decreased overall mortality in relation to reduced cardiovascular and extrahepatic cancer-related events. These results support a beneficial effect of early and sustained management of patients with iron excess, even when mild.
authors.affiliation: CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France. Electronic address: edouard.bardou-jacquet@chu-rennes.fr.
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
authors.affiliation: INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France.
authors.forename: Jeff
authors.initials: J
authors.lastname: Morcet
authors.affiliation: INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Manet
authors.affiliation: CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lainé
authors.affiliation: INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Perrin
authors.affiliation: CHU Rennes, Service de génétique moléculaire, Rennes, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jouanolle
authors.affiliation: CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France; University of Rennes 1, UFR médecine, Rennes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.affiliation: CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France; University of Rennes 1, UFR médecine, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Moirand
authors.affiliation: University of Rennes 1, UFR médecine, Rennes, France; CHU Rennes, Service d'épidémiologie et de santé publique, Hôpital Pontchaillou, Rennes, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viel
authors.affiliation: CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France; INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France; University of Rennes 1, UFR médecine, Rennes, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000401:mortality; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D005602:France / Q000453:epidemiology; D006432:Hemochromatosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins
keywords: Cancer; Cardiovascular disease; HFE; Hemochromatosis; Iron overload; Survival