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Anticancer Res. 2002 Nov-Dec;22(6B):3797-9.

Risk of primary non-hepatocellular malignancies in hereditary hemochromatosis.

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1
Department of Internal Medicine, University of North Dakota School of Medicine, 1919, N Elm Street, Fargo, ND 58102, USA.

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.

MATERIALS AND 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.

CONCLUSION:

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.

PMID:
12552996
[Indexed for MEDLINE]
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