Risk of Hepatocellular Carcinoma in Patients with Various HFE Genotypes

Natarajan, Yamini; Patel, Parth; Chu, Jinna; Xin, Yu; Hernáez, Rubén; El–Serag, Hashem B.; Kanwal, Fasiha

doi:10.1007/s10620-022-07602-9

Cited by 10 publications

(5 citation statements)

References 30 publications

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“…In our study, hepatocellular cancer incidence was not increased in homozygous p.C282Y patients when compared with a propensity score‐matched control cohort. Previous studies reported a higher cancer incidence in p.C282Y homozygotes when compared with matched controls 35–38 . Our study provides longitudinal data on cancer incidence.…”

Section: Discussionsupporting

confidence: 54%

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Penetrance, cancer incidence and survival in HFE haemochromatosis—A population‐based cohort study

Schaefer,

Pammer,

Pfeifer

et al. 2024

Liver International

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Background and AimsHaemochromatosis is characterized by progressive iron overload affecting the liver and can cause cirrhosis and hepatocellular carcinoma. Most haemochromatosis patients are homozygous for p.C282Y in HFE, but only a minority of individuals with this genotype will develop the disease. The aim was to assess the penetrance of iron overload, fibrosis, hepatocellular carcinoma and life expectancy.MethodsA total of 8839 individuals from the Austrian region of Tyrol were genotyped for the p.C282Y variant between 1997 and 2021. Demographic, laboratory parameters and causes of death were assessed from health records. Penetrance, survival, and cancer incidence were ascertained from diagnosed cases, insurance‐ and cancer registry data. Outcomes were compared with a propensity score‐matched control population.ResultsMedian age at diagnosis in 542 p.C282Y homozygous individuals was 47.8 years (64% male). At genotyping, the prevalence of iron overload was 55%. The cumulative penetrance of haemochromatosis defined as the presence of provisional iron overload was 24.2% in males and 10.5% in females aged 60 years or younger. Among p.C282Y homozygotes of the same ages, the cumulative proportion of individuals without fibrosis (FIB‐4 score < 1.3) was 92.8% in males and 96.7% in females. Median life expectancy was reduced by 6.8 years in individuals homozygous for p.C282Y when compared with population‐matched controls (p = .001). Hepatocellular carcinoma incidence was not significantly higher in p.C282Y homozygotes than in controls matched for age and sex.ConclusionReduced survival and the observed age‐dependent increase in penetrance among p.C282Y homozygotes call for earlier diagnosis of haemochromatosis to prevent complications.

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Section: Discussionsupporting

confidence: 54%

“…Previous studies reported a higher cancer incidence in p.C282Y homozygotes when compared with matched controls. [35][36][37][38] Our study provides longitudinal TA B L E 2 Cox regression of life expectancy.…”

Section: Re Sultsmentioning

confidence: 99%

Penetrance, cancer incidence and survival in HFE haemochromatosis—A population‐based cohort study

Schaefer,

Pammer,

Pfeifer

et al. 2024

Liver International

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“…Hemochromatosis is associated with an increased risk for HCC, not just due to liver disease progression to severe fibrosis and cirrhosis. An increased risk was also found in patients without fibrosis, indicated by low APRI values (AST to platelet ratio index) but constantly elevated serum ferritin levels [90].…”

Section: Oxidative Stress and Hepatocellular Carcinoma (Hcc)mentioning

confidence: 89%

Iron, Oxidative Stress, and Metabolic Dysfunction—Associated Steatotic Liver Disease

Gensluckner,

Wernly,

Datz

et al. 2024

Antioxidants

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Excess free iron is a substrate for the formation of reactive oxygen species (ROS), thereby augmenting oxidative stress. Oxidative stress is a well-established cause of organ damage in the liver, the main site of iron storage. Ferroptosis, an iron-dependent mechanism of regulated cell death, has recently been gaining attention in the development of organ damage and the progression of liver disease. We therefore summarize the main mechanisms of iron metabolism, its close connection to oxidative stress and ferroptosis, and its particular relevance to disease mechanisms in metabolic-dysfunction-associated fatty liver disease and potential targets for therapy from a clinical perspective.

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“…A study on breast cancer showed that heme iron intake was significantly associated with increased risk, whereas no associations were found for dietary iron, supplemental iron, or total iron intake (85). Even though the risk of hepatocellular carcinoma is known to be increased in individuals homozygous for hemochromatosis (99), the relation between primary liver cancer and iron intake in the general population is less clear. A recent meta-analysis showed an association between high serum ferritin levels and primary liver cancer but the associations were subject to heterogeneity and it was concluded that further confirmatory studies are needed (100).…”

Section: Iron and Risk Of Cancermentioning

confidence: 99%

Iron – a background article for the Nordic Nutrition Recommendations 2023

Domellöf,

Sjöberg

2024

Food & Nutrition Research

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Iron absorption from foods is generally lower than that of most other nutrients and is highly variable depending on individual iron status and iron bioavailability in the meal. Several large population groups in the Nordic and Baltic countries are at risk of iron deficiency, including infants, young children, menstruating females, pregnant women as well as vegetarians. Iron deficiency leads to anemia, fatigue, and limited capacity for physical activity. Of particular concern is that iron deficiency anemia in young children is associated with impaired neurodevelopment. A comprehensive literature search has been performed and summarized. New factorial calculations have been performed considering iron losses, iron absorption and iron requirements in various population groups. Recent data on iron intakes and the prevalence of iron deficiency in the Nordic countries are presented. Average requirements and tentative recommended intakes are presented for 12 different population groups. Pregnant women and those with high menstrual blood losses should consume iron-rich food and undergo screening for iron deficiency. Infants should consume iron-rich complementary foods and cow’s milk should be avoided as a drink before 12 months of age and limited to < 500 mL/day in toddlers. Vegetarians should consume a diet including wholegrains, legumes, seeds, and green vegetables together with iron absorption enhancers. There is no evidence that iron intake per se increases the risk of cancer or diabetes. Iron absorption from foods is generally lower than that of most other nutrients and can vary between <2 and 50% depending on individual iron status and iron bioavailability in the meal.

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Risk of Hepatocellular Carcinoma in Patients with Various HFE Genotypes

Cited by 10 publications

References 30 publications

Penetrance, cancer incidence and survival in HFE haemochromatosis—A population‐based cohort study

Penetrance, cancer incidence and survival in HFE haemochromatosis—A population‐based cohort study

Iron, Oxidative Stress, and Metabolic Dysfunction—Associated Steatotic Liver Disease

Iron – a background article for the Nordic Nutrition Recommendations 2023

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