Marabelli Monica, Cheng Su-Chun, Parmigiani Giovanni
Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
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.
导致共济失调毛细血管扩张症综合征的基因 ATM 也是一种中度风险的乳腺癌（BC）易感基因。已经开展了大量研究来确定 ATM 基因突变对乳腺癌风险的影响。流行病学队列研究、系谱分析和病例对照研究以不同形式报告了乳腺癌风险，包括外显率、相对风险、标准化发病率和比值比。由于报告的估计值在定性和定量方面都存在差异，我们开发了一个通用模型，用于整合文献中可用的不同类型的癌症风险。我们进行了一项全面的荟萃分析，确定了 19 项研究，并使用我们的模型获得了乳腺癌外显率的共识估计值。我们估计，杂合 ATM 突变携带者在 50 岁时患乳腺癌的累积风险为 6.02%（95%可信区间：4.58 - 7.42%），在 80 岁时为 32.83%（95%可信区间：24.55 - 40.43%）。准确评估癌症外显率对于帮助突变携带者做出能够降低患病几率的医疗和生活方式决策至关重要。
