RISK OF NEOPLASTIC AND OTHER DISEASES AMONG PEOPLE WITH HETEROZYGOSITY FOR HEREDITARY HEMOCHROMATOSIS

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 communi ty-based cohort was defined, in which the exposure variable was hetero zygosity for HH. Heterozygotes were identified by mailing individuals homozygous for HH questionnaires concerning the health histories of th eir parents (predominantly heterozygotes or exposed). Spouses of the H H homozygotes were asked to complete accompanying questionnaires conce rning their parents (unexposed). The frequencies for exposed and unexp osed, age-adjusted relative risks (RR), and 95% confidence intervals ( CI), of cancer, heart disease, and stroke as causes of death as well a s the cumulative incidence of heart attack, diabetes, stroke, hyperten sion, colonic adenoma, and cancers of the lung, colorectum, breast, ce rvix, pancreas, stomach, and blood were estimated. Results. Data were available for 1950 HH heterozygotes and 1656 unexposed subjects. Eleva ted 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), a nd hematologic malignancy (RR, 1.30; CI, 1.30-1.63), for colonic adeno ma 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). Co nclusions. Heterozygosity for HH is associated with increased risk for colorectal neoplasia, diabetes, hematologic malignancy, and gastric c ancer. No increased risk of heart disease, cancer death, or cancers of the lung, breast, or cervix were demonstrated.