Background: Increased body iron stores have been associated with risk of heart attack in men and risk of cancer and colonic adenoma in both sexes. Because heterozygous carriers of hereditary hemochromatosis (HH) have on the average increased iron stores compared with noncarriers of the HH gene and comprise as much as 15% of the American population, disease risk in HH heterozygotes was investigated.
Methods: A community-based cohort was defined, in which the exposure variable was heterozygosity for HH. Heterozygotes were identified by mailing individuals homozygous for HH questionnaires concerning the health histories of their parents (predominantly heterozygotes or exposed). Spouses of the HH homozygotes were asked to complete accompanying questionnaires concerning their parents (unexposed). The frequencies for exposed and unexposed, age-adjusted relative risks (RR), and 95% confidence intervals (CI), of cancer, heart disease, and stroke as causes of death as well as the cumulative incidence of heart attack, diabetes, stroke, hypertension, colonic adenoma, and cancers of the lung, colorectum, breast, cervix, pancreas, stomach, and blood were estimated.
Results: Data were available for 1950 HH heterozygotes and 1656 unexposed subjects. Elevated RR were observed in HH heterozygotes in males for diabetes (RR, 1.16; 95% CI, 1.01-1.33), colorectal cancer (RR, 1.28; CI, 1.07-1.53), and hematologic malignancy (RR, 1.30; CI, 1.30-1.63), for colonic adenoma in females (RR, 1.29; CI, 1.08-1.53) and males (RR, 1.24; CI, 1.05-1.46), and for stomach cancer in females (RR, 1.37; CI, 1.04-1.79).
Conclusions: Heterozygosity for HH is associated with increased risk for colorectal neoplasia, diabetes, hematologic malignancy, and gastric cancer. No increased risk of heart disease, cancer death, or cancers of the lung, breast, or cervix were demonstrated.