Hereditary hemochromatosis gene variant is tied to liver cancer, mortality

  • Atkins JL & al.
  • JAMA
  • 24.11.2020

  • von Jim Kling
  • Studien – kurz & knapp
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Takeaway

  • Homozygosity for the p.C282Y variant is associated with heightened risk for hepatic malignancy and death in men.

Why this matters

  • The p.C282Y variant is present in 81% of people with hemochromatosis, the most common autosomal recessive disorder among people with Northern European ancestry.

Study design

  • Analysis of data for UK Biobank participants of European ancestry (n=451,186).
  • Funding: UK Medical Research Council.

Key results

  • Comparison of homozygosity for HFE p.C282Y vs having neither the HFE p.C282Y nor p.H63D variants:
    • Men had higher risk for:
      • Hepatic malignancies: 1.55% vs 0.14%.
        • HR, 10.47 (P<.001>
      • All-cause mortality: 6.8% vs 5.3%.
        • HR, 1.24 (P=.046).
    • For women, risk values were not statistically significant for hepatic malignancy (HR, 2.06; P=.22) or death (HR, 1.18; P=.20).
  • Lifetable projections showed that by age 75 years, men homozygous for p.C282Y vs those with no variants tied to primary hepatic malignancy had a higher risk for malignancy: 7.2% vs 0.6% (95% CI of difference, 3.5%-12.3%). 
    • Women who were homozygous did not have this higher risk.
  • Risk for death by age 75 years was also higher in men who were homozygous (19.5% vs 15.1%; 95% CI of difference, 1.2%-8.5%).
    • The risk was not higher in women with homozygosity.

Limitations

  • Participants were healthier than the general population.