TY - JOUR
T1 - Penetrance of ATM Gene Mutations in Breast Cancer
T2 - A Meta-Analysis of Different Measures of Risk
AU - Marabelli, Monica
AU - Cheng, Su Chun
AU - Parmigiani, Giovanni
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Ataxia-telangiectasia mutated (ATM) gene
KW - Genetic predisposition
KW - Hereditary breast cancer
KW - Penetrance
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U2 - 10.1002/gepi.21971
DO - 10.1002/gepi.21971
M3 - Article
AN - SCOPUS:84964620308
SN - 0741-0395
JO - Genetic Epidemiology
JF - Genetic Epidemiology
ER -