Spring Holter, Ayelet Borgida, Robert Grant, Kara Semotiuk, and Steven Gallinger, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital; Anna Dodd, David Hedley, Neesha Dhani, Malcolm Moore, and Steven Gallinger, McCain Pancreatic Cancer Centre, University Health Network; and Steven Narod and Mohammad Akbari, Women's College Research Institute, Toronto, Ontario, Canada.
J Clin Oncol. 2015 Oct 1;33(28):3124-9. doi: 10.1200/JCO.2014.59.7401. Epub 2015 May 4.
The main purpose of this study was to determine the prevalence of pathogenic BRCA1 and BRCA2 mutations in a consecutively ascertained clinic-based cohort of patients with pancreatic ductal adenocarcinoma and describe the clinical and family history characteristics.
Unselected, consecutive, incident patients with pancreatic ductal adenocarcinoma were recruited at a single cancer center over a 2-year period. Participants provided blood for DNA analysis and cancer family history, and cancer treatment records were reviewed. DNA from all patients was analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification for germline variants in BRCA1 and BRCA2.
Three hundred six patients were eligible for analysis. Pathogenic germline BRCA mutations were identified in 14 patients (4.6%; 95% CI, 2.2% to 6.9%), including 11 patients with a BRCA2 mutation and three patients with a BRCA1 mutation. Having a cancer family history that met genetic testing criteria of the National Comprehensive Cancer Network or the Ontario Ministry of Health and Long-Term Care or self-reporting as Ashkenazi Jewish was significantly associated with BRCA mutation carrier status (P=.02, P<.001, and P=.05, respectively). However, the majority of the BRCA mutation-positive patients did not actually meet these genetic testing criteria.
Pathogenic BRCA mutations were identified in 4.6% of a large cohort of clinic-based patients. Considering the implications for family members of BRCA carriers, and possibly tailored chemotherapeutic treatment of patients, our finding has implications for broader BRCA genetic testing for patients with pancreatic ductal adenocarcinoma.
本研究的主要目的是确定连续确诊的胰腺导管腺癌临床队列患者中致病性 BRCA1 和 BRCA2 突变的流行率，并描述其临床和家族史特征。
在 2 年期间，在单一癌症中心招募了未经选择的、连续的、偶发性胰腺导管腺癌患者。参与者提供血液进行 DNA 分析和癌症家族史，并回顾癌症治疗记录。对所有患者的 DNA 进行 Sanger 测序和多重连接依赖性探针扩增分析，以检测 BRCA1 和 BRCA2 中的种系变异。
306 名患者符合分析条件。在 14 名患者（4.6%；95%CI，2.2%至 6.9%）中发现了致病性种系 BRCA 突变，包括 11 名 BRCA2 突变患者和 3 名 BRCA1 突变患者。符合国家综合癌症网络或安大略省卫生部和长期护理部的遗传检测标准的癌症家族史或自我报告为 Ashkenazi 犹太人与 BRCA 突变携带者状态显著相关（P=.02，P<.001 和 P=.05，分别）。然而，大多数 BRCA 突变阳性患者实际上不符合这些遗传检测标准。
在大型临床患者队列中，确定了 4.6%的致病性 BRCA 突变。考虑到 BRCA 携带者家庭成员的影响，以及可能对患者进行的靶向化疗治疗，我们的发现对胰腺导管腺癌患者更广泛的 BRCA 遗传检测具有影响。
