Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma

In hepatocellular carcinoma (HCC) iron has been implicated as a risk factor prima ri ly in patients with hereditary haemochromatosis (HH) and cirrhosi s. The wild-type HH (HFE) protein complexes with the transferrin receptor ( TFR), and two HFE mutations (Cys282Tyr and His63Asp) have been found to inc rease the affinity of the TFR for transferrin resulting in an increased cel lular uptake of iron. In previous studies we found an interaction between H FE and TFR genotypes in multiple myeloma and breast and colorectal carcinom as. In the present investigation we have studied HFE and TFR genotypes in 5 4 Swedish patients with HCC, using DNA from archival samples of paraffin wa x blocks. The same HFE-TFR interaction as in the previously studied neoplas tic disorders was found. Individuals carrying the HFE282Tyr allele (homo- a nd heterozygotes) in combination with homozygosity for the TFR Ser allele s howed an increased risk for HCC (OR = 3.5; 95% confidence interval, Cl = 1. 3-9.3), which was further increased in HFE Tyr homozygotes and compound (Ty r/Asp) heterozygotes in combination with TFR 142Ser homozygosity (OR = 17.2 ; 95% Cl = 1.8-168.9). The presence of liver cirrhosis could only be assess ed in part of the patient material. In patients with verified liver cirrhos is the risk figures were substantially increased: for HFE 282 Tyr carriers in combination with TFR 142Ser/Ser OR = 7.2; 95% Cl = 2.0-25.5 and for HFE 282Tyr homozygotes and compound heterozygotes in combination with TFR 142Se r homozygosity, OR = 62.8; 95% CI = 6.1-642.5. Copyright (C) 2000 S. Karger AG, Basel.