Cancer in patients with ataxia-telangiectasia and in their relatives in the Nordic countries

Background: Epidemiologic studies of the families of patients with ataxia-t elangiectasia (A-T), a recessive genetic neurologic disorder caused by muta tion of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incide nce in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. Methods: We conducted a study in the Nordic countr ies of 1218 blood relatives of 56 A-T patients from 50 families. The relati ves were identified from population registries, and the occurrence of cance r was determined from cancer registry files in each country and compared wi th national incidence rates. All statistical tests were two-sided. Results: Among the 56 patients with A-T, we observed six cases of cancer (four leuk emias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yieldin g a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40), Invasive breast cancer occurr ed in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.3 6), including five of the 50 mothers tall of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17), Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, sta tistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. Conclusions: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings s uggest, however, that, even if ATM mutations are responsible for some breas t cancer cases, ATM is a relatively weak genetic risk factor for the diseas e.