Disease risk in hereditary hemochromatosis heterozygotes

HFE C282Y and H63D in adults with malignancies in a community medical oncology practice

“…It is difficult to compare reports of the prevalence of malignancy in cohorts of putative hemochromatosis heterozygotes characterized by phenotype criteria and family relationships [1-4] to those performed using HFE mutation testing. In epidemiology studies that use data modeling techniques, iron phenotype data are typically adjusted for common disease-related variables that cause abnormal serum iron concentrations, transferrin saturation values, or serum ferritin concentrations values, thus excluding many study subjects from final analysis [2,51].…”

“…Thus, using phenotype criteria to identify C282Y or H63D heterozygotes is often unreliable. In some studies, presumed hemochromatosis heterozygotes were ascertained only by self-reported kinship to a putative hemochromatosis homozygote in questionnaire surveys [53]. In family-based studies in which HFE mutation or other DNA-based testing is not used, non-paternity is an additional source of error (1.0 – 1.4% non-paternity in American Caucasians) [54,55].…”

“…An increased prevalence of certain types of malignancy has been reported in putative hemochromatosis heterozygotes characterized by iron phenotype criteria or family studies [1-4]. However, discovery of the HFE gene on Ch6p and two common hemochromatosis-associated HFE missense mutations C282Y (exon 4; nt 845G→A) and H63D (exon 2; nt 187 C→G) [5] permits definition of hemochromatosis heterozygosity using molecular criteria.…”