通过多基因panel 检测鉴定出 BRIP1、RAD51C 和 RAD51D 突变携带者的卵巢癌诊断年龄。
Age of ovarian cancer diagnosis among BRIP1, RAD51C, and RAD51D mutation carriers identified through multi-gene panel testing.
机构信息
Myriad Genetics Inc., Salt Lake City, UT, USA.
The Rush Cancer Institute, Rush University, 1725 W. Harrison St. #309, Chicago, IL, 60612, USA.
出版信息
J Ovarian Res. 2021 Apr 29;14(1):61. doi: 10.1186/s13048-021-00809-w.
BACKGROUND
Professional society guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) for women with pathogenic variants (PVs) in ovarian cancer-risk genes. Personalization of that intervention is based on gene-specific phenotypes; however, the age of ovarian cancer diagnosis in women with PVs in moderate penetrance ovarian cancer-risk genes is not well characterized. Women who had hereditary cancer panel testing from September 2013-May 2019 were included (N = 631,950). Clinical/demographic information was compared for women with a PV in BRIP1, RAD51C, or RAD51D versus in BRCA1 or BRCA2.
RESULTS
PVs in BRIP1, RAD51C, or RAD51D were identified in 0.5% of all tested women but in 1.6% of women with a history of ovarian cancer (~ 3-fold increase). PVs in BRCA1 or BRCA2 were identified in 2.4% of all tested women but in 6.1% of women with a history of ovarian cancer (~ 2.5-fold increase). The proportion of women with a personal or family history of ovarian cancer was similar among women with a PV in BRIP1, RAD51C, RAD51D, BRCA1, or BRCA2. The median age at ovarian cancer diagnosis was 53 years for BRCA1, 59 years for BRCA2, 65 years for BRIP1, 62 years for RAD51C, and 57 years for RAD51D.
CONCLUSIONS
These data reinforce the importance of identifying PVs in moderate penetrance ovarian cancer-risk genes. The age at ovarian cancer diagnosis was older for women with PVs in BRIP1, RAD51C, or RAD51D, suggesting that it is safe to delay RRSO until age 45-50 in RAD51D PV carriers and possibly until age 50-55 in BRIP and RAD51C PV carriers.
背景
专业学会指南建议对携带卵巢癌风险基因致病性变异（PVs）的女性行预防性输卵管卵巢切除术（RRSO）。该干预措施的个体化基于基因特异性表型；然而，携带中等外显率卵巢癌风险基因的 PV 女性的卵巢癌诊断年龄尚未得到很好的描述。本研究纳入了 2013 年 9 月至 2019 年 5 月间接受遗传性癌症panel 检测的女性（N=631950）。比较了携带 BRIP1、RAD51C 或 RAD51D 基因 PV 与携带 BRCA1 或 BRCA2 基因 PV 的女性的临床/人口统计学信息。
结果
所有检测女性中，BRIP1、RAD51C 或 RAD51D 基因的 PV 发生率为 0.5%，但卵巢癌病史女性中该比例上升至 1.6%（约 3 倍）。BRCA1 或 BRCA2 基因的 PV 发生率为 2.4%，但卵巢癌病史女性中该比例上升至 6.1%（约 2.5 倍）。BRIP1、RAD51C、RAD51D、BRCA1 或 BRCA2 基因的 PV 女性中，有个人或家族卵巢癌病史的比例相似。BRCA1 基因的卵巢癌中位诊断年龄为 53 岁，BRCA2 为 59 岁，BRIP1 为 65 岁，RAD51C 为 62 岁，RAD51D 为 57 岁。
结论
这些数据强调了识别中等外显率卵巢癌风险基因 PV 的重要性。携带 BRIP1、RAD51C 或 RAD51D 基因 PV 的女性卵巢癌诊断年龄更大，这表明 RAD51D 基因 PV 携带者可安全延迟 RRSO 至 45-50 岁，BRIP 和 RAD51C 基因 PV 携带者可延迟至 50-55 岁。
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