HFE and Tangier disease: Most individuals (80–90%) affected by hemochromatosis (iron overload) are homozygous for the Cys282Tyr substitution. HFE variant His63Asp has a very low penetrance and mild expressivity for iron overload [67]. HFE Cys282Tyr variant allele is associated with breast cancer [68], colorectal cancer [69], and hepatocellular carcinoma [70].