Heterozygous ATM mutations do not contribute to early onset of breast cancer

Nat Genet. 1997 Mar;15(3):307-10. doi: 10.1038/ng0397-307.


Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition, attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene. AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise approximately 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer, raising the possibility that germline ATM mutations may account for approximately 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years. To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Asian Americans
  • Ataxia Telangiectasia Mutated Proteins
  • Base Sequence
  • Blacks / genetics
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / physiopathology*
  • Cell Cycle Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Exons
  • Female
  • Frameshift Mutation
  • Genetic Carrier Screening
  • Humans
  • Introns
  • Jews
  • Leucine Zippers
  • Middle Aged
  • Point Mutation
  • Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • Sequence Deletion
  • Tumor Suppressor Proteins
  • United States


  • Cell Cycle Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases