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

Monica Marabelli, Su Chun Cheng, Giovanni Parmigiani

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
JournalGenetic Epidemiology
StateAccepted/In press - 2016
Externally publishedYes


  • Ataxia-telangiectasia mutated (ATM) gene
  • Genetic predisposition
  • Hereditary breast cancer
  • Penetrance

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

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