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Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark
A W Hsing1, J K McLaughlin, J H Olsen
1Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD.
Insights
Men diagnosed with primary hemochromatosis face a significantly higher risk of developing primary liver cancer. This iron overload condition also elevates the risk for non-hepatic cancers, including esophageal cancer and skin melanoma.
Area of Science:
- Hepatology
- Oncology
- Epidemiology
Background:
- Primary hemochromatosis is an iron overload disorder.
- The association between hemochromatosis and cancer risk requires further investigation.
Purpose of the Study:
- To assess the subsequent cancer risk in a population-based cohort of Danish men diagnosed with primary hemochromatosis.
Main Methods:
- Population-based cohort study of 120 Danish men diagnosed with primary hemochromatosis between 1977 and 1989.
- Follow-up until 1989 to track cancer incidence.
- Standardized incidence ratios (SIR) were calculated to compare observed cancer cases with expected rates.
Main Results:
- A significantly elevated risk of primary liver cancer was observed (SIR 92.9), including hepatocellular carcinoma and cholangiocarcinoma, particularly in patients with cirrhosis.
- Elevated risks were also found for non-hepatic cancers (SIR 3.5), specifically esophageal cancer (SIR 42.9) and skin melanoma (SIR 27.8).
Conclusions:
- Patients with primary hemochromatosis have a substantial risk of developing primary liver cancer.
- The study supports the hypothesis linking hemochromatosis to increased liver cancer risk.
- Further research is warranted to clarify the relationship between non-hepatic malignancies and iron stores in the general population.
Abstract:
A population-based cohort of 120 Danish men, discharged with a hospital diagnosis of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for subsequent cancer risk. Nineteen subjects (including 6 with primary liver cancers) were excluded from the analysis, either because they died within the same month of hemochromatosis diagnosis or because they had cancer prior to diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver cancers occurred one year or more after the diagnosis of hemochromatosis, far surpassing the expected number based on incidence rates from the Danish population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to 237.9). The excess of liver cancer was associated with cirrhosis and included cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9 to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this population-based study are in accordance with the hypothesis that patients with primary hemochromatosis have a substantial risk of primary liver cancer. Further studies of hemochromatosis may be useful in clarifying the relation of non-hepatic malignancies to body iron stores in the general population.