ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles

We screened individuals from 443 familial breast cancer pedigrees and 521 controls for ATM sequence variants and identified 12 mutations in affected individuals and two in controls (P = 0.0047). The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% confidence interval (c.i.) = 1.51–3.78, P = 0.0003). There was no evidence that other classes of ATM variant confer a risk of breast cancer.

[1]  A. Tward,et al.  Cancer risk in ATM heterozygotes: a model of phenotypic and mechanistic differences between missense and truncating mutations. , 1999, Molecular genetics and metabolism.

[2]  Y. Shiloh.  ATM and related protein kinases: safeguarding genome integrity , 2003, Nature Reviews Cancer.

[3]  Nazneen Rahman,et al.  Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations , 2002, Nature Genetics.

[4]  M. Swift,et al.  Breast and other cancers in families with ataxia-telangiectasia. , 1987, The New England journal of medicine.

[5]  D. Easton,et al.  EMGM Abstracts , 2003, Genetic epidemiology.

[6]  Sara G. Becker-Catania,et al.  Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity. , 2000, Molecular genetics and metabolism.

[7]  E. Ostrander,et al.  Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history , 2001, Cancer.

[8]  J. Sambrook,et al.  Dominant negative ATM mutations in breast cancer families. , 2002, Journal of the National Cancer Institute.

[9]  Lesley McGuffog,et al.  Cancer risks and mortality in heterozygous ATM mutation carriers. , 2005, Journal of the National Cancer Institute.

[10]  K. Isselbacher,et al.  Heterozygous ATM mutations do not contribute to early onset of breast cancer , 1997, Nature Genetics.

[11]  A. Børresen-Dale,et al.  Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia , 2005, British Journal of Cancer.

[12]  Nazneen Rahman,et al.  CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. , 2004, American journal of human genetics.

[13]  M. Jung,et al.  ATM missense mutations are frequent in patients with breast cancer. , 2003, Cancer genetics and cytogenetics.