title: Risk of primary non-hepatocellular malignancies in hereditary hemochromatosis.
abstract: OBJECTIVE
  The relationship between hemochromatosis, a genetic iron disorder, and the risk of hepatocellular carcinoma is well-documented. However, the true incidence of non-hepatocellular malignancies remains ill defined. We performed a retrospective cohort study to identify a possible association between hereditary hemochromatosis and the development of non-hepatocellular carcinomas.
  
  
  METHODS
  After appropriate institutional review board approval, an extensive chart review was completed on all patients with hereditary hemochromatosis diagnosed between 1986 and 2001. The diagnosis was based on either a genetic study to identify the Cys282Tyr and the His63Asp mutations on the HLA-H gene and/or hepatic tissue diagnosis, in conjunction with a treatment history of therapeutic phlebotomy. Data collection also included documentation of associated malignancies, the presence of co-morbid medical illnesses, and risk factors for cancer. Our database was age-standardized to the United States population using the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program data to obtain a standardized incidence ratio (SIR) of non-hepatocellular malignancies in our study population.
  
  
  RESULTS
  Fifty-nine patients (49 males, 10 females) with a mean age of 46 years (range: 10-68 years) met the criteria for the diagnosis of hereditary hemochromatosis. Of these, 13 patients (22%) had a biopsy-proven diagnosis of a primary non-hepatocellular malignancy giving an age-adjusted SIR of 1.40 (p < 0.04). Histologically, the types of malignancy included: 3 patients with colorectal cancer; 2 patients with gastric carcinoma, 3 patients with prostate cancer; 2 patients with breast cancer; 1 patient with acute myelogenous leukemia, one patient with Hodgkin's lymphoma and one patient with non-Hodgkin's lymphoma.
  
  
  CONCLUSIONS
  While an association between hemochromatosis and hepatocellular carcinoma is well-described, there also appears to be a relationship between hemochromatosis and the development of non-hepatocellular malignancies. Since increased iron stores alone have not been proven to be premalignant in recent studies, interplay between genetic factors in hemochromatosis may play a role as a risk factor in the development of an associated malignancy. Larger cohorts of subjects with hereditary iron overload disorders are needed to confirm our findings. Furthermore, if a causal association between hemochromatosis and common carcinomas does indeed exist, such patients may be candidates for individualized, rigorous cancer screening programs.
authors.affiliation: Department of Internal Medicine, University of North Dakota School of Medicine, 1919, N Elm Street, Fargo, ND 58102, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Geier
authors.forename: Brian
authors.initials: B
authors.lastname: Hebert
authors.forename: Anil
authors.initials: A
authors.lastname: Potti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D002648:Child; D015331:Cohort Studies; D005260:Female; D006432:Hemochromatosis / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D012189:Retrospective Studies