The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Survival and Causes of Death in Cirrhotic and in Noncirrhotic Patients with Primary Hemochromatosis
Niederau, C., Fischer, R., Sonnenberg, A., Stremmel, W., Trampisch, H. J., & Strohmeyer, G. W. (1985) · New England Journal of Medicine · doi:10.1056/nejm198511143132004 · Cited by 1,063
Long-term survival in patients with hereditary hemochromatosis
Niederau, C., Fischer, R., Pürschel, A., Stremmel, W., Häussinger, D., & Strohmeyer, G. W. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8613000 · Cited by 885
Penetrance of 845G→A (C282Y) HFE hereditary haemochromatosis mutation in the USA
Beutler, E., Felitti, V. J., Koziol, J. A., Ho, N. J., & Gelbart, T. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07447-0 · Cited by 823
Prevalence of Hemochromatosis among 11,065 Presumably Healthy Blood Donors
Edwards, C. Q., Griffen, L. M., Goldgar, D. E., Drummond, C., Skolnick, M. H., & Kushner, J. P. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805263182103 · Cited by 628
Body Iron Stores and the Risk of Cancer
Stevens, R. G., Jones, D. Y., Micozzi, M. S., & Taylor, P. R. (1988) · New England Journal of Medicine · doi:10.1056/nejm198810203191603 · Cited by 575
Iron-induced carcinogenesis: The role of redox regulation
Toyokuni, S. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)02111-6 · Cited by 568
Mattsson, B., & Wallgren, A. (1984) · Acta Radiologica Oncology · doi:10.3109/02841868409136026 · Cited by 558
HFE Gene and Hereditary Hemochromatosis: A HuGE Review
Hanson, E. H. (2001) · American Journal of Epidemiology · doi:10.1093/aje/154.3.193 · Cited by 435
Jazwinska, E. C., Cullen, L. M., Busfield, F., Pyper, W. R., Webb, S. I., Powell, L. W., Morris, C. P., & Walsh, T. P. (1996) · Nature Genetics · doi:10.1038/ng1196-249 · Cited by 419
Jouanolle, A. M., Gandon, G., Jézéquel, P., Blayau, M., Campion, M. L., Yaouanq, J., Mosser, J., Fergelot, P., Chauvel, B., Bouric, P., et al. (1996) · Nature Genetics · doi:10.1038/ng1196-251 · Cited by 338
Body iron stores and risk of cancer
Knekt, P., Reunanen, A., Takkunen, H., Aromaa, A., Heliövaara, M., & Hakuunen, T. (1994) · International Journal of Cancer · doi:10.1002/ijc.2910560315 · Cited by 314
Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis
Fletcher, L. M., Dixon, J. L., Purdie, D. M., Powell, L. W., & Crawford, D. H. (2002) · Gastroenterology · doi:10.1053/gast.2002.30992 · Cited by 285
Clinical and Biochemical Abnormalities in People Heterozygous for Hemochromatosis
Bulaj, Z. J., Griffen, L. M., Jorde, L. B., Edwards, C. Q., & Kushner, J. P. (1996) · New England Journal of Medicine · doi:10.1056/nejm199612123352403 · Cited by 283
Prospective study of chemoprevention of hepatocellular carcinoma with sho-saiko-to (TJ-9)
Oka, H., Yamamoto, S., Kuroki, T., Harihara, S., MARUMO, T., Kim, S. R., Monna, T., Kobayashi, K., & Tango, T. (1995) · Cancer · doi:10.1002/1097-0142(19950901)76:5 · Cited by 271
Fracanzani, A. L. (2001) · Hepatology · doi:10.1053/jhep.2001.22506 · Cited by 248
Long-term survival analysis in hereditary hemochromatosis
Adams, P. C., Speechley, M. R., & Kertesz, A. E. (1991) · Gastroenterology · doi:10.1016/0016-5085(91)90013-b · Cited by 242
The person-number systems of Sweden, Norway, Denmark, and Israel.
As, L., Lundeborg, S., Gs, L., Thygesen, L. C., & Huebner, J. (1980) · PubMed · Cited by 206
Surival and Prognostic Factors in 212 Italian Patients With Genetic Hemochromatosis
Fargion, S. R., Mandelli, C., Piperno, A., Cesana, B. M., Fracanzani, A. L., Fraquelli, M., Bianchi, P. A., Fiorelli, G., & Conte, D. (1992) · Hepatology · doi:10.1002/hep.1840150417 · Cited by 199
Bradbear, R. A., Bain, C. J., Siskind, V., Schofield, F. D., Webb, S. I., Axelsen, E., Halliday, J. W., Bassett, M. L., & Powell, L. W. (1985) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/75.1.81 · Cited by 195
Crawford, D. H., Jazwinska, E. C., Cullen, L. M., & Powell, L. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70320-8 · Cited by 166
Yang, Q., McDonnell, S. M., Khoury, M. J., Cono, J., & Parrish, R. G. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-129-11_part_2-199812011-00005 · Cited by 150
Persson, G., Boström, G., Diderichsen, F., Lindberg, G., Pettersson, B., Rosén, M., Stenbeck, M., & Wall, S. (2001) · Scandinavian Journal of Public Health · doi:10.1177/14034948010290032901 · Cited by 148
Cancer risk following primary hemochromatosis: A population‐based cohort study in Denmark
Hsing, A. W., McLaughlin, J. K., Olsen, J. H., Mellemkjar, L., Wacholder, S., & Fraumeni, J. F. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910600204 · Cited by 145
Association Between Hemochromatosis (HFE) Gene Mutation Carrier Status and the Risk of Colon Cancer
Shaheen, N. J., Silverman, L. M., Keku, T. O., Lawrence, L. B., Rohlfs, E. M., Martin, C. F., Galanko, J., & Sandler, R. S. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.2.154 · Cited by 130
Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis
Fargion, S. R., Fracanzani, A. L., Piperno, A., Braga, M., D’Alba, R., Ronchi, G., & Fiorelli, G. (1994) · Hepatology · doi:10.1002/hep.1840200608 · Cited by 111
HFE mutations in patients with hereditary haemochromatosis in Sweden
Cardoso, E. M., Stal, P. I., Hagen, Cabeda, Cabeda, Esin, Sousa, D., & Hultcrantz (1998) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1998.00270.x · Cited by 104
Beckman, L. E. (1999) · Carcinogenesis · doi:10.1093/carcin/20.7.1231 · Cited by 100
Hultén, L., Gramatkovski, E., Gleerup, A., & Hallberg, L. (1995) · PubMed · Cited by 95
Brissot, P., Moirand, R., Jouanolle, A., Guyader, D., Gall, J. L., Deugnier, Y., & David, V. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80188-3 · Cited by 89
van Asperen, I. A., Feskens, E. J. M., Bowles, C. H., & Kromhout, D. (1995) · International Journal of Epidemiology · doi:10.1093/ije/24.4.665 · Cited by 70
Deshpande, A. (2002) · Toxicological Sciences · doi:10.1093/toxsci/67.2.275 · Cited by 61
High Incidence of Extrahepatic Carcinomas in Idiopathic Hemochromatosis
Ammann, R., Müller, E., Bansky, J., Schüler, G., & Häcki, W. H. (1980) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365528009181523 · Cited by 52
Underdiagnosis of hereditary haemochromatosis: lack of presentation or penetration?
Ryan, E. M., Byrnes, V., Coughlan, B., Flanagan, A.-M., Barrett, S., O’Keane, J. C., & Crowe, S. F. (2002) · Gut · doi:10.1136/gut.51.1.108 · Cited by 47
Höhler, T., Leininger, S., Köhler, H. H., Schirmacher, P., & Galle, P. R. (2000) · Liver International · doi:10.1034/j.1600-0676.2000.020006482.x · Cited by 44
Lucotte, G. (2001) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2001.0417 · Cited by 37
Macdonald, G. A., Tarish, J., Whitehall, V., Sally, J.-C., Mellick, G. D., Buttenshaw, R. L., Johnson, A. G., Young, J. P., & Leggett, B. (1999) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.1999.02027.x · Cited by 36
Tiniakos, G., & Williams, R. C. (1988) · PubMed · Cited by 32
Biochemical expression of heterozygous hereditary hemochromatosis
Valk, B. D., Witlox, R. S. G. M., van der Schouw, Y. T., & Marx, J. J. M. (2000) · European Journal of Internal Medicine · doi:10.1016/s0953-6205(00)00111-4 · Cited by 27
Hereditary hemochromatosis and alcohol: A fibrogenic cocktail
Britton, R. S., & Bacon, B. R. (2002) · Gastroenterology · doi:10.1053/gast.2002.31652 · Cited by 23
Boström, G. (2001) · PubMed · Cited by 6
Chapter 6. Habits of Life and Public Health
Bostrom, G. (2001) · Scandinavian Journal of Public Health · doi:10.1177/14034948010290033601 · Cited by 3
Flagged first, then by citations
Research works printed but not linked: 2
- Tiniakos, 1988, Cirrhotic process, liver cell carcinoma and extrahepatic malignant tumors in idiopathic haemochromatosis, Appl Pathol, 6, 128
- Hulten, 1995, Iron absorption from the whole diet, Eur J Clin Nutr, 49, 794
Cited by
Sorted by citations
Management of Hepatocellular Carcinoma *
Bruix, J., & Sherman, M. (2005) · Hepatology · doi:10.1002/hep.20933 · Cited by 5,913
Marrero, J. A., Kulik, L., Sirlin, C. B., Zhu, A. X., Finn, R. S., Abecassis, M. M., Roberts, L. R., & Heimbach, J. K. (2018) · Hepatology · doi:10.1002/hep.29913 · Cited by 4,597
“9%.(51) In a recent systematic review, a total of 6,528 patients with autoimmune hepatitis (AIH) had a median follow-up of 8 years were evaluated for HCC incidence.”
BackgroundHepatocellular carcinoma in cirrhosis: Incidence and risk factors
Fattovich, G., Stroffolini, T., Zagni, I., & Donato, F. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.09.014 · Cited by 2,587
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Martin, P., DiMartini, A., Feng, S., Brown, R., & Fallon, M. (2014) · Hepatology · doi:10.1002/hep.26972 · Cited by 1,045
“5% of women, most often but not always in those with cirrhosis.(166,167) The risk of HCC in cirrhosis due to hereditary hemochromatosis appears to be greater than in other causes of cirrhosis.”
Background
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
