West Allison H, Blazer Kathleen R, Stoll Jessica, Jones Matthew, Weipert Caroline M, Nielsen Sarah M, Kupfer Sonia S, Weitzel Jeffrey N, Olopade Olufunmilayo I
Section of Hematology/Oncology, The University of Chicago Comprehensive Cancer Center, 5841 S. Maryland Avenue, MC2115, Chicago, IL, 60637-1470, USA.
Division of Clinical Cancer Genomics, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
Fam Cancer. 2018 Oct;17(4):495-505. doi: 10.1007/s10689-018-0070-x.
Comprehensive genomic cancer risk assessment (GCRA) helps patients, family members, and providers make informed choices about cancer screening, surgical and chemotherapeutic risk reduction, and genetically targeted cancer therapies. The increasing availability of multigene panel tests for clinical applications allows testing of well-defined high-risk genes, as well as moderate-risk genes, for which the penetrance and spectrum of cancer risk are less well characterized. Moderate-risk genes are defined as genes that, when altered by a pathogenic variant, confer a 2 to fivefold relative risk of cancer. Two such genes included on many comprehensive cancer panels are the DNA repair genes ATM and CHEK2, best known for moderately increased risk of breast cancer development. However, the impact of screening and preventative interventions and spectrum of cancer risk beyond breast cancer associated with ATM and/or CHEK2 variants remain less well characterized. We convened a large, multidisciplinary, cross-sectional panel of GCRA clinicians to review challenging, peer-submitted cases of patients identified with ATM or CHEK2 variants. This paper summarizes the inter-professional case discussion and recommendations generated during the session, the level of concordance with respect to recommendations between the academic and community clinician participants for each case, and potential barriers to implementing recommended care in various practice settings.
全面基因组癌症风险评估（GCRA）有助于患者、家庭成员和医疗服务提供者在癌症筛查、手术及化疗风险降低以及基因靶向癌症治疗方面做出明智选择。用于临床应用的多基因检测越来越普及，这使得对明确的高风险基因以及中度风险基因进行检测成为可能，而对于中度风险基因，其癌症风险的外显率和范围特征尚不明确。中度风险基因被定义为当被致病性变异改变时，会使患癌相对风险增加2至5倍的基因。许多综合癌症检测面板中包含的两个此类基因是DNA修复基因ATM和CHEK2，它们因乳腺癌发生风险适度增加而最为人所知。然而，与ATM和/或CHEK2变异相关的筛查和预防性干预的影响以及乳腺癌以外的癌症风险范围仍不太清楚。我们召集了一个由GCRA临床医生组成的大型多学科横断面小组，以审查同行提交的具有挑战性的、被鉴定出携带ATM或CHEK2变异的患者病例。本文总结了会议期间的跨专业病例讨论和建议、学术和社区临床医生参与者在每个病例的建议方面的一致程度，以及在各种实践环境中实施推荐治疗的潜在障碍。
