Wárlám-Rodenhuis Carla C, Koot Veronica C M, van der Luijt Rob B, Vasen Hans F A, Ausems Margreet G E M
Department of Radiation Oncology, University Medical Center, GA Utrecht, The Netherlands.
Eur J Cancer. 2005 Jul;41(10):1409-15. doi: 10.1016/j.ejca.2005.02.030.
We prospectively screened a hospital-based population of 1000 successive breast cancer patients receiving adjuvant radiotherapy for predictive factors associated with the presence of BRCA1 and BRCA2 mutations. We offered genetic counseling and DNA analysis to selected patients. About 52% of patients showed at least one presumed predictive factor. Hundred and thirty-seven patients underwent DNA analysis. We identified 14 deleterious mutations (10.2%, 95% CI: 5.2-15.3%): 8 BRCA1 mutations and 6 BRCA2 mutations and 14 variants of uncertain clinical significance. Ovarian cancer in the family history was the only factor significantly associated with the presence of a disease-causing mutation (P < 0.01). Eight of the 14 (57%) mutation carriers had no affected first-degree relatives and in 4 of these there was no family history of breast or ovarian cancer. Clinicians should offer genetic counseling and DNA testing to breast cancer patients from families with breast and ovarian cancer, and to patients who are younger than 45 years when they are diagnosed with breast cancer.
我们前瞻性地筛查了1000例连续接受辅助放疗的乳腺癌患者，以寻找与BRCA1和BRCA2基因突变相关的预测因素。我们为选定的患者提供了遗传咨询和DNA分析。约52%的患者显示至少有一个推测的预测因素。137例患者接受了DNA分析。我们鉴定出14个有害突变（10.2%，95%置信区间：5.2 - 15.3%）：8个BRCA1突变和6个BRCA2突变以及14个临床意义不确定的变异。家族史中有卵巢癌是与致病突变存在显著相关的唯一因素（P < 0.01）。14名（57%）突变携带者中有8人没有受影响的一级亲属，其中4人没有乳腺癌或卵巢癌家族史。临床医生应为来自乳腺癌和卵巢癌家族的乳腺癌患者，以及45岁以下被诊断为乳腺癌的患者提供遗传咨询和DNA检测。
