A prospective cohort study with 12-year follow-up of 203 C282Y homozygotes of Northern European descent aged 40–69 years in Australia found that 28.4% of men, but only 1.2% of women had documented iron-overload-related disease (cirrhosis, liver fibrosis, hepatocellular carcinoma, elevated aminotransferase levels, physician-diagnosed symptomatic hemochromatosis, or arthropathy of second or third MCP joints). Only one non-C282Y homozygote had iron-overload-related disease.
Comment: The quality of evidence is upgraded by large magnitude of effect (large difference between men and women)