Haemochromatosis and gastrointestinal cancer

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Iron overload in patients with haemochromatosis is a strong risk factor for liver cancer, but its influence on other gastrointestinal cancer risk is unclear. The aim was to assess the relative risk of luminal gastrointestinal cancer among patients diagnosed with haemochromatosis. This population-based, nationwide Swedish cohort study included patients with haemochromatosis in Sweden in 1965–2013. The incidence of gastrointestinal cancers was assessed through the Swedish Cancer Registry. The measure of relative risk was the standardised incidence ratio (SIR) with 95% confidence interval (CI), that is, the ratio of the observed number of gastrointestinal cancers in the haemochromatosis cohort divided by the expected number of such cancers, calculated from the entire corresponding background population of Sweden. Among 6,849 patients in the haemochromatosis cohort with up to 48 years of follow-up, the SIRs were 3-fold increased for oesophageal squamous cell carcinoma (SIR = 3.2, 95% CI 1.3–6.6; n = 7) and 40% increased for colon adenocarcinoma (SIR = 1.4, 95% CI 1.1–1.9; n = 54). No associations were found between haemochromatosis and the risk of adenocarcinoma of the oesophagus (SIR = 0.5, 95% CI 0.0–2.5; n = 1), stomach (SIR = 0.7, 95% CI 0.3–1.4; n = 8), small bowel (SIR = 1.2, 95% CI 0.0–6.7; n = 1) or rectum (SIR = 1.0, 95% CI 0.6–1.6; n = 21). These findings indicate that haemochromatosis increases the risk of oesophageal squamous cell carcinoma and colon adenocarcinoma, but might not influence the risk of other types of luminal gastrointestinal cancer. These findings should encourage further research examining the role of iron overload in cancer aetiology.

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Hemochromatosis causes iron overload, resulting in increased oxidative stress and potentially fueling the proliferation of tumor cells. It remains unclear, however, whether iron overload promotes cancer development in hemochromatosis patients. In this population-based study involving nearly 7,000 hemochromatosis patients in Sweden, the iron disorder was strongly associated with liver cancer and was linked to increased risk of esophageal squamous cell carcinoma and colon cancer. No association was found for gastric or rectal cancers, however. Further investigation of a possible role for iron overload in the development of non-hepatic gastrointestinal cancer is needed.

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