title: Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries.
abstract: 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.
authors.affiliation: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. jorgen@cancer.dk
authors.forename: J H
authors.initials: JH
authors.lastname: Olsen
authors.forename: J M
authors.initials: JM
authors.lastname: Hahnemann
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: K
authors.initials: K
authors.lastname: Brøndum-Nielsen
authors.forename: L
authors.initials: L
authors.lastname: Hammarström
authors.forename: R
authors.initials: R
authors.lastname: Kleinerman
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: T
authors.initials: T
authors.lastname: Lönnqvist
authors.forename: R
authors.initials: R
authors.lastname: Sankila
authors.forename: N
authors.initials: N
authors.lastname: Seersholm
authors.forename: S
authors.initials: S
authors.lastname: Tretli
authors.forename: J
authors.initials: J
authors.lastname: Yuen
authors.forename: J D
authors.initials: JD
authors.lastname: Boice
authors.forename: M
authors.initials: M
authors.lastname: Tucker
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001260:Ataxia Telangiectasia / Q000150:complications* / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D003241:Consanguinity; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D011159:Population Surveillance; D012042:Registries; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology