Penetrance of ATM Gene Mutations in Breast Cancer: A Meta-Analysis of Different Measures of Risk.
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.
Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
Monica
M
Marabelli
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Su-Chun
SC
Cheng
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Giovanni
G
Parmigiani
D000328:Adult; D000367:Age Factors; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008019:Life Style; D008957:Models, Genetic; D009154:Mutation; D019683:Penetrance; D012307:Risk Factors
D064007:Ataxia Telangiectasia Mutated Proteins
ataxia-telangiectasia mutated (ATM) gene; genetic predisposition; hereditary breast cancer; penetrance