EFFECTS OF PRECONCEPTIONAL IRRADIATION ON MORTALITY AND CANCER INCIDENCE IN THE OFFSPRING OF PATIENTS GIVEN INJECTIONS OF THOROTRAST

Background: Findings from a British case-control study suggest that a preconceptional paternal external radiation dose of more than 100 mSv (10 rem) is significantly related to risk for leukemia and non-Hodgkin 's lymphoma in offspring. The suggestion, however, has not been suppor ted by experimental or other epidemiologic studies. Purpose: The purpo se of this study was to investigate if preconceptional irradiation of males and females from internally deposited radionuclides affects mort ality and risk of developing cancer in their offspring. Methods: The o ffspring of 260 females (n = 143) and 320 males (n = 226) who lived lo nger than 1 year after receiving Thorotrast (a compound no longer in u se) for cerebral arteriography were studied for mortality rate and the risk for developing cancer. Thorotrast was used as a contrast medium containing a 20% colloidal solution of thorium dioxide-Th 232, an alph a particle-emitting radionuclide, which is retained lifelong in nearly all organs. The offspring of the exposed patients were identified by manual linkage with the municipal population registers and followed-up for vital status by computerized linkage with the Danish National Cen tral Population Registry and for incidence of cancer by computerized l inkage with the Danish National Cancer Registry. The standardized mort ality/morbidity ratios (SMRs) for death and for site-specific incidenc e of cancer in the offspring were calculated as ratios of the observed rates in the study population to the expected rates in the general po pulation. Results: After a median follow-up of 40 years, four cases of cancer (breast [one], uterine cervix [one], melanoma of skin [one], a nd retinoblastoma [one]) versus 2.9 cases expected, developed among 14 3 children born to mothers who received injections of Thorotrast (SMR = 1.4; 95% confidence interval [CI] = 0.4-3.5), while six cases of can cer (one case each of cancer of lung, testis, thyroid, and Hodgkin's l ymphoma and two cases of melanoma of skin), versus 4.5 expected, occur red among 226 children of exposed fathers (SMR = 1.3; 95% CI = 0.5-2.9 ). No case of leukemia or non-Hodgkin''s lymphoma occurred in any of t he offspring studied. Mortality was lower than expected both for child ren of exposed mothers (SMR = 0.7; 95% CI = 0.3-1.5) and of exposed fa thers (SMR = 0.5; 95% CI = 0.2-1.0). Conclusions: This study does not support the previously proposed association between parental exposure to radiation and the risk of childhood leukemia and lymphoma. Furtherm ore, since mortality from all causes was not increased in any offsprin g, our results do not support the belief that preconceptional parental low-dose exposure to alpha radiation increases the incidence of cance r or mortality in the offspring.