Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-26T20:35:56.775Z Has data issue: false hasContentIssue false

Ataxia-Telangiectasia genes and breast cancer risk in a French family study

Published online by Cambridge University Press:  22 July 2005

Nadine Andrieu
Affiliation:
Inserm Emi 00-06, Tour Evry 2, 523 Place des Terrasses de l'Agora, 91034 Evry Cedex France Institut Curie, Service de Biostatistiques, 26 rue d'Ulm, 75248 Paris Cedex 05, France
Eve Cavaciuti
Affiliation:
Inserm Emi 00-06, Tour Evry 2, 523 Place des Terrasses de l'Agora, 91034 Evry Cedex France Institut Curie, Service de Biostatistiques, 26 rue d'Ulm, 75248 Paris Cedex 05, France
Anthony Laugé
Affiliation:
Institut Curie, Service de Génétique Oncologique, 26 rue d'Ulm, 75248 Paris Cedex 05, France
Katia Ossian
Affiliation:
Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
Nicolas Janin
Affiliation:
Département de Génétique Humaine, CHU Sart Tilman, 4000 Liège, Belgique
Janet Hall
Affiliation:
International Agency for Research on Cancer, DNA Repair Team, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France
Dominique Stoppa-Lyonnet
Affiliation:
Institut Curie, Service de Génétique Oncologique, 26 rue d'Ulm, 75248 Paris Cedex 05, France

Abstract

Ataxia-telangiectasia (AT) is a rare autosomal recessive early childhood disorder, characterized by progressive neuronal degeneration, immunological deficiency, radiosensitivity and an increased risk of cancer caused in most cases by mutations in the AT-mutated gene (ATM). Epidemiological studies on AT families have shown that AT heterozygous women have an increased risk of developing breast cancer (BC). The ATM protein plays a central role in the recognition and repair of DNA double-strand breaks and the subsequent activation of cell-cycle checkpoints. Whilst AT is a rare disease, 0·5–1% of the general population are estimated to be AT mutation carriers, thus any increases in the risks of cancer associated with ATM carrier status are of public health relevance. The main results of our published studies on the risk of BC in 34 French AT families according to heterozygote status, type of ATM mutation and exogenous factors are summarized here. The risk of BC was higher in ATM heterozygous (HetATM) women and did not differ significantly according to the type of ATM mutation (missense vs truncating) carried by the AT family members but appeared associated with the position of some truncating mutations in certain binding domains of the ATM protein. The effect of exogenous factors, such as reproductive life factors and exposure to ionizing radiation, on the risk of BC according to ATM heterozygote status was assessed. There was no evidence for interaction (except for age at first full-term pregnancy). These findings does not appear to justify a separate screening program from that already available to other women with a first-degree relative affected by BC, as their risks have similar amplitude. Chest X-rays did not appear to be a risk factor for BC in our study population. More powerful studies, using data sets pooled from international sources are being set up to confirm these observations.

Type
Research Article
Copyright
Proprietors of Journal of Dairy Research 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)