Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.
Weill Cornell Medicine-Qatar, Ar-Rayyan, Qatar.
Breast Cancer Res Treat. 2022 Jan;191(1):31-38. doi: 10.1007/s10549-021-06413-2. Epub 2021 Oct 13.
Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance.
A search query was developed to identify MBC-related papers indexed in PubMed/MEDLINE. A validated natural language processing method was applied to identify papers reporting penetrance estimates. These penetrance studies' bibliographies were reviewed to ensure comprehensiveness. We accessed the potential ascertainment bias for each enrolled study.
Fifteen penetrance studies were identified from 12,182 abstracts, covering five purported MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2. Cohort (n = 6, 40%) and case-control (n = 5, 33%) studies were the two most common study designs, followed by family-based (n = 3, 20%), and a kin-cohort study (n = 1, 7%). Seven of the 15 studies (47%) adjusted for ascertainment adequately and therefore the MBC risks reported by these seven studies can be considered applicable to the general population. Based on these seven studies, we found pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 show an increased risk for MBC. The association between BRCA1 and MBC was not statistically significant.
This work supports the conclusion that pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 increase the risk of MBC, whereas pathogenic variants in BRCA1 may not be associated with increased MBC risk.
已经确定了几个男性乳腺癌（MBC）易感基因，但这些基因中每个基因的致病性变异个体的 MBC 风险（即外显率）尚不清楚。我们对报告 MBC 易感性基因外显率的研究进行了系统回顾，以更好地总结当前外显率的估计值。
制定了一个搜索查询，以确定在 PubMed/MEDLINE 中索引的与 MBC 相关的论文。应用经过验证的自然语言处理方法来识别报告外显率估计值的论文。回顾这些外显率研究的参考文献，以确保全面性。我们评估了每个纳入研究的潜在确定偏倚。
从 12182 篇摘要中确定了 15 项外显率研究，涵盖了五个假定的 MBC 易感性基因：ATM、BRCA1、BRCA2、CHEK2 和 PALB2。队列（n=6，40%）和病例对照（n=5，33%）研究是最常见的两种研究设计，其次是基于家族的（n=3，20%）和亲属队列研究（n=1，7%）。15 项研究中有 7 项（47%）充分调整了确定因素，因此这 7 项研究报告的 MBC 风险可被认为适用于一般人群。基于这 7 项研究，我们发现 ATM、BRCA2、CHEK2 c.1100delC 和 PALB2 的致病性变异增加了 MBC 的风险。BRCA1 与 MBC 之间的关联没有统计学意义。
这项工作支持了以下结论：ATM、BRCA2、CHEK2 c.1100delC 和 PALB2 中的致病性变异增加了 MBC 的风险，而 BRCA1 中的致病性变异可能与增加的 MBC 风险无关。
