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Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers

Hagström, Hannes ; Ndegwa, Nelson ; Jalmeus, Molly ; Ekstedt, Mattias ; Posserud, Iris ; Rorsman, Fredrik ; Nyhlin, Nils ; Klintman, Daniel LU ; Werner, Mårten and Marschall, Hanns Ulrich , et al. (2021) In Liver International 41(3). p.545-553
Abstract

Background & Aims: Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods: We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast... (More)

Background & Aims: Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods: We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinson’s disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. Results: Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of <1%. Conclusions: Individuals found to be HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
C282Y, epidemiology, H63D, hemochromatosis, prognosis
in
Liver International
volume
41
issue
3
pages
545 - 553
publisher
Wiley-Blackwell
external identifiers
  • pmid:33450138
  • scopus:85099978527
ISSN
1478-3223
DOI
10.1111/liv.14792
language
English
LU publication?
no
id
525c7167-b980-426f-b381-d63d82579a48
date added to LUP
2021-02-10 09:36:26
date last changed
2022-08-11 20:17:26
@article{525c7167-b980-426f-b381-d63d82579a48,
  abstract     = {{<p>Background &amp; Aims: Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods: We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinson’s disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. Results: Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of &lt;1%. Conclusions: Individuals found to be HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.</p>}},
  author       = {{Hagström, Hannes and Ndegwa, Nelson and Jalmeus, Molly and Ekstedt, Mattias and Posserud, Iris and Rorsman, Fredrik and Nyhlin, Nils and Klintman, Daniel and Werner, Mårten and Marschall, Hanns Ulrich and Askling, Johan and Stål, Per}},
  issn         = {{1478-3223}},
  keywords     = {{C282Y; epidemiology; H63D; hemochromatosis; prognosis}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{545--553}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Liver International}},
  title        = {{Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers}},
  url          = {{http://dx.doi.org/10.1111/liv.14792}},
  doi          = {{10.1111/liv.14792}},
  volume       = {{41}},
  year         = {{2021}},
}