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Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives
Open accessAbstract
Background & aims Iron overload may be carcinogenic. Patients with hereditary hemochromatosis (HH) are reportedly at a 20-200-fold risk of intrahepatic cancer, but the reported risks for nonhepatobiliary cancers are conflicting. The risk of cancer in heterozygous individuals (estimated allele frequency, 1/10 to 1/20) is unknown. This study aimed to better assess these risks. Methods We performed a population-based cohort study of 1847 Swedish patients with HH and 5973 of their first-degree relatives using nationwide, population-based health and census registers. We used standardized incidence ratios (SIRs) as relative risk. Results With 62 liver cancers and 128 nonhepatobiliary cancers, patients with HH were at a 20-fold risk of liver cancer (SIR, 21; 95% confidence interval [CI], 16-22) but an almost unaltered risk of all other cancers (SIR, 1.2; 95% CI, 1.0-1.4), including nonelevated risks for several gastrointestinal tract cancers. At 10 years of follow-up, the absolute risk of liver cancer was 6% among men and 1.5% among women. With 21 liver cancers and 508 nonhepatobiliary cancers, first-degree relatives were at an unaltered risk of extrahepatic cancer (SIR, 1.0; 95% CI, 0.9-1.1, including unelevated risks for gastrointestinal cancers) but at a modest and historic increased risk of hepatobiliary cancer (SIR, 1.5; 95% CI, 1.0-2.4), the histopathologic spectrum of which differed from the patients. Conclusions Patients (particularly men) with HH are at increased risk for hepatocellular cancer, although the magnitude of the risk is lower than previous estimates. Overall cancer risk in first-degree relatives does not seem to be increased.
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“Murine erythroleukemia cells that overexpress ferritin H displayed lower levels of the labile iron pool and ROS (78).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [78]
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“Accumulating evidence shows that ferritin acts as an antioxidant protein (59, 60, 78, 159, 227, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [78]
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“induction of ferritin mRNA was observed in mouse liver (303) and erythroid cells (78) treated with oxidative stress–inducing compounds.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [78]
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“overexpression or knockdown of ferritin expression in mammalian cells has proven the cytoprotective role of ferritin under prooxidative conditions (59, 60, 78, 159, 227, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [78]
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Surveillance for Hepatocellular Carcinoma
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Delima, R. D., Chua, A. C. G., Tirnitz‐Parker, J. E. E., Gan, E. K., Croft, K. D., Graham, R. M., Olynyk, J. K., & Trinder, D. (2012) · Hepatology · doi:10.1002/hep.25689 · Cited by 55
“LPO-induced DNA lesions are increased 2- to 3-fold in the livers of HH patients and, together with the iron overload observed in HH, are associated with an approximately 20-fold increased risk of hepatocellular carcinoma.(15,16) Oxidative stress has been shown to activate apoptosis and necrosis, promoting the synthesi…”
BackgroundHepatocellular Carcinoma and Other Malignancies in Autoimmune Hepatitis
Czaja, A. J. (2013) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2525-5 · Cited by 55
Prevention of mutation, Cancer, and other Age-Associated diseases by optimizing micronutrient intake
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“[117] Elmberg M, Hultcrantz R, Ekbom A, et al.”
BackgroundLi, S., Saviano, A., Erstad, D. J., Hoshida, Y., Fuchs, B. C., Baumert, T., & Tanabe, K. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9123817 · Cited by 46
“The risk of HCC in patients with hemochromatosis is approximately 20 times higher than the general population [86].”
BackgroundHepatocellular Carcinoma: State of the Art Imaging and Recent Advances
Navin, P. J., & Venkatesh, S. K. (2019) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2018.00032 · Cited by 49
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Screening for hepatocellular carcinoma
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Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy
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Trace Element Concentration in Primary Liver Cancers—A Systematic Review
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“The incidence of HCC in primary hemochromatosis is around 20–200 times higher than in the normal population [26–29].”
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“respect to properly matched patients with nonhemochromatosis liver diseases,(4) results on extrahepatic cancers are contradictory.(5) The results reported by Zacharski et al.”
ResultOutcome of liver transplantation in hereditary hemochromatosis
Dar, F. S., Faraj, W. G., Zaman, M. B., Bartlett, A. S., Bomford, A. B., O’Sullivan, A., O’Grady, J., Heneghan, M. A., Rela, M., & Heaton, N. D. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00863.x · Cited by 45
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Elmberg, M., Hultcrantz, R. W., Simard, J. F., Carlsson, Å., & Askling, J. (2012) · Arthritis Care & Research · doi:10.1002/acr.21883 · Cited by 44
“In contrast to these studies, our study showed only a slight increased risk of OA but no other joint disease in FDRs of patients with GH (48).”
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The antioxidant status of the plasma in patients with breast cancer undergoing chemotherapy
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“Studies linked increased serum iron to the development of cancer [51,52].”
BackgroundNrf2 Is a Potential Modulator for Orchestrating Iron Homeostasis and Redox Balance in Cancer Cells
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Hepatocellular Carcinoma in Asia: A Challenging Situation
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“chronic HBV and HCV infections, alcoholic hepatitis, Aflatoxin B1 [3–5], and some diseases inherited by monogenic and polygenic mechanisms [18–30] (Table 1).”
BackgroundPathological investigation of oxidative stress in the post‐genomic era
Toyokuni, S., & Akatsuka, S. (2007) · Pathology International · doi:10.1111/j.1440-1827.2007.02127.x · Cited by 40
Prevention of hepatocellular carcinoma in nonviral‐related liver diseases
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Metadata
- Authors
- Elmberg, M., Hultcrantz, R., Ekbom, A., Brandt, L., Olsson, S., Olsson, R., Lindgren, S., Lööf, L., Stål, P., Wallerstedt, S., Almer, S., Sandberg-Gertzén, H., & Askling, J.
- Affiliations
- Karolinska University Hospital (SE)
- Sahlgrenska University Hospital (SE)
- Uppsala University Hospital (SE)
- Linköping University Hospital (SE)
- Corresponding author
- Elmberg, Maria
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 125
- Issue
- 6
- Pages
- 1733-1741
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2165680505
- Cited by
- 273
- References
- 41
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 14 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 14 · 2019: 12 · 2018: 8 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 15 · 2013: 19 · 2012: 17
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Cancerfonden
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hereditary hemochromatosis, cancer risk, iron overload, hepatocellular carcinoma, liver cancer, gastrointestinal cancer, first-degree relatives, heterozygous carriers, familial cancer risk
- MeSH terms
- Hemochromatosis Protein, Adolescent, Adult, Aged, Aged, 80 and over, Female, Hemochromatosis, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Membrane Proteins, Middle Aged, Mutation, Risk, Histocompatibility Antigens Class I
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