Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia

• Published in: British journal of cancer Vol. 93; no. 2; pp. 260 - 265
• Main Authors: OLSEN, J. H, HAHNEMANN, J. M. D, BRØNDUM-NIELSEN, K, YUEN, J, TUCKER, M, BØRRESEN-DALE, A.-L, TRETLI, S, KLEINERMAN, R, SANKILA, R, HAMMARSTRÖM, L, ROBSAHM, T. E, KÄÄRIÄINEN, H, BREGARD, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 25.07.2005
• Subjects: Adult; Age Factors; Aged; Ataxia; Ataxia Telangiectasia - complications; Ataxia Telangiectasia - genetics; Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Cancer research; Cell Cycle Proteins - genetics; Denmark - epidemiology; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Epidemiology; Female; Finland - epidemiology; Genetics and Genomics; Humans; Incidence; Leucine Zippers; Medical research; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Mutation; Norway - epidemiology; Pediatrics; Pedigree; Protein Serine-Threonine Kinases - genetics; Risk Factors; Sweden - epidemiology; Tumor Suppressor Proteins - genetics; Tumors; Denmark; Sweden; Norway; Finland; Human; Skin disease; Nervous system diseases; ATM heterozygosity; early-onset breast cancer; Cardiovascular disease; cancer predisposition; Breast cancer; Malignant tumor; Blood; Genetic disease; Heterozygosity; Vascular disease; Mammary gland diseases; Eye disease; Cancerology; Age of onset; Predisposition; Ataxia telangiectasia; Familial cancer; Genetics
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602658

Epidemiological studies have consistently shown elevated rates of breast cancer among female blood relatives of patients with ataxia telangiectasia (AT), a rare autosomal recessive disease. A large proportion of the members of AT families are carriers of AT-causing gene mutations in ATM (Ataxia Telangiectasia Mutated), and it has been hypothesised that these otherwise healthy carriers are predisposed to breast cancer. This is an extended and enlarged follow-up study of cancer incidence in blood relatives of 75 patients with verified AT in 66 Nordic families. Blood relatives were identified through population registry linkages, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. The ATM mutation carrier probabilities of relatives were assigned from the combined information on location in family, consanguinity, if any, and supplementary carrier screening in some families. Among the 1445 blood relatives of AT patients, 225 cancers were observed, with 170.4 expected, yielding a standardised incidence ratio (SIR) of 1.3 (95% confidence interval (CI), 1.1-1.4). Invasive breast cancer occurred in 34 female relatives (SIR, 1.7; 95% CI, 1.2-2.4) and was diagnosed in 21 women before the age of 55 years (SIR, 2.9; 95% CI, 1.8-4.5), including seven mothers of probands (SIR, 8.1; 95% CI, 3.3-17). When the group of mothers was excluded, no clear relationship was observed between the allocated mutation carrier probability of each family member and the extent of breast cancer risk. We concluded that the increased risk for female breast cancer seen in 66 Nordic AT families appeared to be restricted to women under the age of 55 years and was due mainly to a very high risk in the group of mothers. The findings of breast cancer risk in mothers, but not other likely mutation carriers, in this and other studies raises questions about the hypothesis of a simple causal relationship with ATM heterozygosity.