Liver Cancer 10-times More Likely in Men with HFE p.C282Y Homozygous Haemochromatosis

Dawn O'Shea

December 01, 2020

Among men, HFE p.C282Y homozygosity is significantly associated with increased risk for liver cancer and excess mortality, according to an article published in  JAMA.

Hereditary haemochromatosis is predominantly caused by the HFE p.C282Y homozygous pathogenic variant. Liver carcinoma and mortality risks are increased in individuals with clinically diagnosed hereditary haemochromatosis, but risks are unclear in mostly undiagnosed p.C282Y homozygotes identified in community genotyping.

Research led by the University of Exeter examined 451,186 male and female UK Biobank participants of European ancestry (aged 40-70 years) with HFE p.C282Y and p.H63D genotypes compared with those with neither HFE variants. Follow-up was from baseline assessment (2006-2010) until January 2018.

Among the 1294 male p.C282Y homozygotes, there were 21 incident hepatic malignancies, 10 of which were in participants without a diagnosis of haemochromatosis at baseline. p.C282Y homozygous men had a higher risk of hepatic malignancies (HR, 10.47; 95% CI, 6.56-16.69; P<.001) and all-cause mortality (n=88; HR, 1.24; 95% CI, 1.004-1.53; P=.046) compared with men with neither HFE variant.

In projections for male p.C282Y homozygotes to age 75 years, the risk of primary hepatic malignancy was 7.2 per cent (95% CI, 3.9%-13.1%) compared with 0.6 per cent (95% CI, 0.4%-0.7%) for men with neither variant. The risk of death was 19.5 per cent (95% CI, 15.8%-24.0%) vs 15.1 per cent (95% CI, 14.7%-15.5%).

Among female p.C282Y homozygotes (n=1596), there were three incident hepatic malignancies and 60 deaths. Associations between homozygosity and hepatic malignancy (HR, 2.06; 95% CI, 0.66-6.49; P=.22) and death (HR, 1.18; 95% CI, 0.91-1.52; P=.20) were not statistically significant.

Atkins JL, Pilling LC, Masoli JAH, Kuo CL, Shearman JD, Adams PC, Melzer D. Association of Hemochromatosis HFE p.C282Y Homozygosity With Hepatic Malignancy. JAMA. 2020;324(20):2048-2057. doi: 10.1001/jama.2020.21566. PMID: 33231665 View abstract

This article originally appeared on Univadis, part of the Medscape Professional Network.


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