© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 2, 121-127,
January 17, 2001
© 2001 Oxford University Press
Cancer in Patients With Ataxia-Telangiectasia and in Their Relatives in the Nordic Countries
Affiliations of authors: J. H. Olsen, N. Seersholm, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; J. M. Hahnemann, K. Brøndum-Nielsen, John F. Kennedy Institute, Glostrup, Denmark; A.-L. Børresen-Dale, Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, Oslo, Norway; L. Hammarström, Division of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Huddinge Sweden; R. Kleinerman, M. Tucker, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; H. Kääriäinen, Department of Medical Genetics, Family Federation of Finland, Helsinki; T. Lönnqvist, Unit of Child Neurology, Hospital for Children and Adolescents, University of Helsinki; R. Sankila, Finnish Cancer Registry, Helsinki; S. Tretli, Cancer Registry of Norway, Institute of Epidemiological Cancer Research, Oslo; J. Yuen, Swedish University of Agricultural Sciences, Uppsala, Sweden; J. D. Boice, Jr., Division of Cancer Epidemiology and Genetics, National Cancer Institute, and International Epidemiology Institute, Rockville, MD.
Correspondence to: Jørgen H. Olsen, M.D., D.M.Sc., Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark (e-mail: jorgen{at}cancer.dk).
Background: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. Methods: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. Results: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding 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 occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all 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, statistically 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 suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.
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