Penetrance of ATM Gene Mutations in Breast Cancer: A Meta-Analysis of Different Measures of Risk

Genet Epidemiol. 2016 Jul;40(5):425-31. doi: 10.1002/gepi.21971. Epub 2016 Apr 25.


The gene responsible for ataxia-telangiectasia syndrome, ATM, is also an intermediate-risk breast cancer (BC) susceptibility gene. Numerous studies have been carried out to determine the contribution of ATM gene mutations to BC risk. Epidemiological cohorts, segregation analyses, and case-control studies reported BC risk in different forms, including penetrance, relative risk, standardized incidence ratio, and odds ratio. Because the reported estimates vary both qualitatively and quantitatively, we developed a general model allowing the integration of the different types of cancer risk available in the literature. We performed a comprehensive meta-analysis identifying 19 studies, and used our model to obtain a consensus estimate of BC penetrance. We estimated the cumulative risk of BC in heterozygous ATM mutation carriers to be 6.02% by 50 years of age (95% credible interval: 4.58-7.42%) and 32.83% by 80 years of age (95% credible interval: 24.55-40.43%). An accurate assessment of cancer penetrance is crucial to help mutation carriers make medical and lifestyle decisions that can reduce their chances of developing the disease.

Keywords: ataxia-telangiectasia mutated (ATM) gene; genetic predisposition; hereditary breast cancer; penetrance.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Databases, Factual
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Life Style
  • Models, Genetic
  • Mutation
  • Penetrance
  • Risk Factors


  • Ataxia Telangiectasia Mutated Proteins