Abstract：
Multigene panel testing now allows efficient testing of many cancer susceptibility genes leading to a larger number of mutation carriers being identified. They need to be counseled about their cancer risk conferred by the specific gene mutation. An important cancer susceptibility gene is PALB2. Multiple studies reported risk estimates for breast cancer (BC) conferred by pathogenic variants in PALB2. Due to the diverse modalities of reported risk estimates (age-specific risk, odds ratio, relative risk, and standardized incidence ratio) and effect sizes, a meta-analysis combining these estimates is necessary to accurately counsel patients with this mutation. However, this is not trivial due to heterogeneity of studies in terms of study design and risk measure. We utilized a recently proposed Bayesian random-effects meta-analysis method that can synthesize estimates from such heterogeneous studies. We applied this method to combine estimates from 12 studies on BC risk for carriers of pathogenic PALB2 mutations. The estimated overall (meta-analysis-based) risk of BC is 12.80% (6.11%-22.59%) by age 50 and 48.47% (36.05%-61.74%) by age 80. Pathogenic mutations in PALB2 makes women more susceptible to BC. Our risk estimates can help clinically manage patients carrying pathogenic variants in PALB2.
摘要：
现在，多基因小组测试可以有效地测试许多癌症易感性基因，从而识别出更多的突变携带者。他们需要就特定基因突变赋予的癌症风险进行咨询。重要的癌症易感基因是PALB2。多项研究报告了PALB2致病变异所赋予的乳腺癌（BC）的风险估计。由于报告的风险估计的不同模式(特定年龄风险，赔率比,相对风险，和标准化发病率)和效应大小，结合这些估计的荟萃分析对于准确地为有此突变的患者提供建议是必要的.然而,由于研究设计和风险度量方面的异质性,这并非微不足道.我们利用了最近提出的贝叶斯随机效应荟萃分析方法，该方法可以综合来自此类异质研究的估计。我们应用此方法结合了12项关于致病性PALB2突变携带者的BC风险研究的估计。到50岁时，BC的估计总体风险（基于荟萃分析）为12.80％（6.11％-22.59％），到80岁时为48.47％（36.05％-61.74％）。PALB2的致病突变使女性更容易患BC。我们的风险估计可以帮助临床管理携带PALB2致病变异的患者。
