Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non–iron-related chronic liver disease

Fracanzani, Anna Ludovica; Conte, Dario; Fraquelli, Mirella; Taioli, Emanuela; Mattioli, Michela; Losco, Alessandra; Fargion, Silvia

doi:10.1053/jhep.2001.22506

Cited by 222 publications

(148 citation statements)

References 28 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…(Most of the untreated patients were from an era before the introduction of phlebotomy therapy; some were patients who refused treatment or were diagnosed at autopsy). In two recent studies 20% [84] and 21% [85] of cirrhotic patients with hemochromatosis developed this tumor. Non-cirrhotic patients also appear to be at risk.…”

Section: Treatment Of Iron Overloadmentioning

confidence: 92%

Iron storage disease: Facts, fiction and progress

Beutler

2007

Blood Cells, Molecules, and Diseases

View full text Add to dashboard Cite

There are many forms of iron storage disease, some hereditary and some acquired. The most common of the hereditary forms is HFE-associated hemochromatosis, and it is this disorder that is the main focus of this presentation. The body iron content is regulated by controlling absorption, and studies in the past decade have clarified, in part, how this regulation functions. A 25 amino acid peptide hepcidin is upregulated by iron and by inflammation, and it inhibits iron absorption and traps iron in macrophages by binding to and causing degradation of the iron transport protein ferroportin. Most forms of hemochromatosis results from dysregulation of hepcidin or defects of hepcidin or ferroportin themselves.Hereditary hemochromatosis was once considered to be very rare, but in the 1970s and 1980s, with the introduction of better diagnostic tests, it became to be considered the most common disease of Europeans. Controlled epidemiologic studies carried out in the last decade have shown, however, the disease itself actually is rare, and it is only the genotype and associated biochemical changes that are common. We do not understand why only a few homozygotes develop severe disease. It now seems unlikely that there are important modifying genes, and although alcohol is known to have some effect, excess drinking probably plays only a modest role in determining the hemochromatosis phenotype.Hereditary hemochromatosis is readily treated by phlebotomy. Secondary forms of the disease require chelation therapy, and the recent introduction of effective oral chelating agents is an important step forward in treating patients with disorders in which iron overload often proves to be fatal, such as thalassemia, myelodysplastic anemias, and dyserythropoietic anemias.While much has been learned about the regulation of iron homeostasis in the past decade, many mysteries remain and represent challenges that will keep us occupied for years to come.It is a great honor for me to present this lecture in memory of my good friend Bracha Ramot. It is because this lecture is in honor of Bracha that I do not feel the least bit uncomfortable speaking about iron storage diseases in a symposium entitled "Genomics and Molecular Biology of Hematopoietic Malignancies". I know that had it been possible to ask her whether this might be appropriate Bracha would have said: "Of course, Ernie. Talk about whatever you want to". That was her way. And, of course, Bracha was no stranger to iron metabolism. She was scientifically broad, a Renaissance hematologist. A MEDLINE search reveals 261 publications by Bracha and eight of those deal with iron --iron in thalassemia, iron in sideroblastic anemia, and iron in iron deficiency anemia.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable...

show abstract

Section: Treatment Of Iron Overloadmentioning

confidence: 92%

Iron storage disease: Facts, fiction and progress

Beutler

2007

Blood Cells, Molecules, and Diseases

View full text Add to dashboard Cite

show abstract

“…HCC complicating HH is most commonly attributed (in 70-95% of patients) to homozygosity for the C282Y mutation of the HFE gene [7,[9][10][11][12][13]. This mutation impairs the expression of HFE protein on cell membranes, thereby compromising iron sensing by hepatocytes and the transcription and release of hepcidin [14]. Inappropriately low secretion of hepcidin is postulated to be the mechanism for the consequent iron overload [6].…”

Section: Hepatic Iron Overload In Hereditary Hemochromatosismentioning

confidence: 99%

“…HCC accounts for as many as 45% of deaths in patients afflicted with HH [11][12][13][14]. A relative risk of tumor formation in the iron-loaded liver of between 20 and 200 has been calculated [11][12][13][14].…”

Section: Hepatocellular Carcinoma In Hereditary Hemochromatosismentioning

confidence: 99%

See 1 more Smart Citation

Hepatic iron overload and hepatocellular carcinoma

Kew

2009

Cancer Letters

108

View full text Add to dashboard Cite

In recent years it has become increasingly evident that excess body iron may be complicated by the supervention of hepatocellular carcinoma (HCC). Hereditary hemochromatosis (HH) was the first condition in which hepatic iron overload was shown to predispose to the development of HCC. The inherited predisposition to excessive absorption of dietary iron in HH is almost always the result of homozygosity of the C282Y mutation of the HFE gene, which causes inappropriately low secretion of hepcidin. HCC develops in 8-10% of patients with HH and is responsible for approximately 45% of deaths in the HCC patients. Cirrhosis is almost always present when HCC is diagnosed. Dietary iron overload is a condition which occurs in rural-dwelling Black Africans in southern Africa as a result of the consumption, over time, of large volumes of alcohol home-brewed in iron containers and having, as a consequence, a high iron content. Iron loading of the liver results and may be complicated by malignant transformation of the liver (relative risk of approximately 10.0). Accompanying cirrhosis does occur but is less common than that in HH. The development of HCC as a consequence of increased dietary iron, and the fact that it may develop in the absence of cirrhosis, has been confirmed in an animal model. Drinking water with a high iron content might contribute to the high incidence of HCC in parts of Taiwan. The metabolic syndrome [obesity, insulin resistance type 2 (or diabetes mellitus type 2), non-alcoholic fatty liver or non-alcoholic steatohepatitis] has in recent years become a major public health problem in some resource-rich countries. A link between excess body iron and insulin resistance or the metabolic syndrome has become apparent. The metabolic syndrome may be complicated by the supervention of HCC, and recent evidence suggests that increased body iron may contribute to this complication.

show abstract

“…1 The risk of HCC developing in HH patients is higher than that of patients with non-HH-related chronic liver diseases, matched for sex, age, and severity of liver fibrosis. 2 It has been shown in case-control studies that African subjects with dietary iron overload have a higher HCC risk as well. 3 Moreover, HCC has been described in several patients with transfusion-associated iron overload or iron overload related to ineffective erythropoiesis.…”

mentioning

confidence: 99%