Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
JCO Precis Oncol. 2023 Sep;7:e2300137. doi: 10.1200/PO.23.00137.
To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC).
Patients with pathologically confirmed EOC who underwent clinical tumor-normal sequencing from January 1, 2015, to December 31, 2020, inclusive of germline analysis of ≥76 genes were included. Patients with newly identified PVs were referred for Clinical Genetics Service (CGS) counseling. Ancestry groups were defined using self-reported race/ethnicity and Ashkenazi Jewish (AJ) heritage. Genetic ancestry was inferred computationally using validated algorithms. Logistic regression models were built.
Of 1,266 patients, self-reported ancestry (AJ, 17%; Asian, 10%; Black/African American, 5.4%; Hispanic, 6.2%; non-Hispanic White, 57%; other, 0.16%; unknown, 4.0%) correlated with genetic ancestry (AJ ancestry, 18%; admixed, 10%; African, 4%; East Asian [EAS], 6%; European, 56%; Native American, 0.2%; South Asian [SAS], 4%; unknown, 2%). Germline PVs were observed in 313 (25%) patients, including 195 (15%) with PVs in EOC-associated genes. Those with PVs were younger at diagnosis (59 62 years; < .001) and more likely to have high-grade serous ovarian cancer (83% 72%; = .009). PV prevalence varied between ancestry groups ( < .001), with highest rates in the AJ (39.9%) and Asian (26.5%) groups and similar rates (>10%) across other ancestry groups. Use of genetic ancestry demonstrated similar findings and further characterized high rates of PV in EAS/SAS groups. Younger age, high-grade serous histology, and self-reported AJ or Asian ancestry were associated with PV in an EOC-associated gene. Rates of CGS counseling for newly identified PVs were high (80%) across ancestry groups.
Rates of PV, particularly in EOC-associated genes, were high regardless of ancestry, with similar rates of counseling between groups, emphasizing the importance of universal genetic testing in all patients with EOC.
评估上皮性卵巢癌（EOC）患者种系致病性/可能致病性变异（PVs）的发生率和按种族进行遗传咨询。
纳入了 2015 年 1 月 1 日至 2020 年 12 月 31 日期间接受临床肿瘤-正常测序且种系分析至少 76 个基因的病理证实为 EOC 的患者。发现新的 PV 患者将被推荐接受临床遗传学服务（CGS）咨询。采用自我报告的种族/民族和阿什肯纳兹犹太人（AJ）血统定义种族群体。采用经过验证的算法进行遗传祖先的计算推断。建立逻辑回归模型。
在 1266 名患者中，自我报告的种族（AJ，17%；亚洲人，10%；黑种人/非裔美国人，5.4%；西班牙裔，6.2%；非西班牙裔白人，57%；其他，0.16%；未知，4.0%）与遗传祖先（AJ 血统，18%；混血，10%；非洲人，4%；东亚人 [EAS]，6%；欧洲人，56%；美洲原住民，0.2%；南亚人 [SAS]，4%；未知，2%）相关。313 名（25%）患者中发现种系 PV，包括 195 名（15%）EOC 相关基因的 PV 患者。PV 患者的诊断年龄较小（59 62 岁；<.001），且更可能患有高级别浆液性卵巢癌（83% 72%；=.009）。不同种族群体之间的 PV 发生率存在差异（<.001），AJ（39.9%）和亚洲（26.5%）组的发生率最高，其他组的发生率相似（>10%）。遗传祖先的使用得出了相似的结果，并进一步表明 EAS/SAS 组的 PV 发生率较高。年轻、高级别浆液性组织学和自我报告的 AJ 或亚洲血统与 EOC 相关基因中的 PV 相关。在所有患者中，新发现的 PVs 的 CGS 咨询率都很高（80%），无论其种族如何。
无论种族如何，PV 的发生率均较高，尤其是在 EOC 相关基因中，各组之间的咨询率相似，这强调了在所有 EOC 患者中进行通用基因检测的重要性。
