title: Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives.
abstract: OBJECTIVE
  Iron overload may be carcinogenic. Patients with hereditary hemochromatosis (HH) are reportedly at a 20-200-fold risk of intrahepatic cancer, but the reported risks for nonhepatobiliary cancers are conflicting. The risk of cancer in heterozygous individuals (estimated allele frequency, 1/10 to 1/20) is unknown. This study aimed to better assess these risks.
  
  
  METHODS
  We performed a population-based cohort study of 1847 Swedish patients with HH and 5973 of their first-degree relatives using nationwide, population-based health and census registers. We used standardized incidence ratios (SIRs) as relative risk.
  
  
  RESULTS
  With 62 liver cancers and 128 nonhepatobiliary cancers, patients with HH were at a 20-fold risk of liver cancer (SIR, 21; 95% confidence interval [CI], 16-22) but an almost unaltered risk of all other cancers (SIR, 1.2; 95% CI, 1.0-1.4), including nonelevated risks for several gastrointestinal tract cancers. At 10 years of follow-up, the absolute risk of liver cancer was 6% among men and 1.5% among women. With 21 liver cancers and 508 nonhepatobiliary cancers, first-degree relatives were at an unaltered risk of extrahepatic cancer (SIR, 1.0; 95% CI, 0.9-1.1, including unelevated risks for gastrointestinal cancers) but at a modest and historic increased risk of hepatobiliary cancer (SIR, 1.5; 95% CI, 1.0-2.4), the histopathologic spectrum of which differed from the patients.
  
  
  CONCLUSIONS
  Patients (particularly men) with HH are at increased risk for hepatocellular cancer, although the magnitude of the risk is lower than previous estimates. Overall cancer risk in first-degree relatives does not seem to be increased.
authors.affiliation: Department of Gastroenterology and Hepatology, Karolinska Hospital, Stockholm, Sweden. maria.elmberg@ks.se
authors.forename: Maria
authors.initials: M
authors.lastname: Elmberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Hultcrantz
authors.forename: Anders
authors.initials: A
authors.lastname: Ekbom
authors.forename: Lena
authors.initials: L
authors.lastname: Brandt
authors.forename: Sigvard
authors.initials: S
authors.lastname: Olsson
authors.forename: Rolf
authors.initials: R
authors.lastname: Olsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Lindgren
authors.forename: Lars
authors.initials: L
authors.lastname: Lööf
authors.forename: Per
authors.initials: P
authors.lastname: Stål
authors.forename: Sven
authors.initials: S
authors.lastname: Wallerstedt
authors.forename: Sven
authors.initials: S
authors.lastname: Almer
authors.forename: Hanna
authors.initials: H
authors.lastname: Sandberg-Gertzén
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics; D005260:Female; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D012306:Risk
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins