Nizic-Kos Tea, Krajc Mateja, Blatnik Ana, Stegel Vida, Skerl Petra, Novakovic Srdjan, Gazic Barbara, Besic Nikola
Department of Surgical Oncology, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia.
Cancer Genetics Clinic, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia.
Ann Surg Oncol. 2021 May;28(5):2561-2570. doi: 10.1245/s10434-020-09178-y. Epub 2020 Oct 8.
Currently, data on pathogenic variants in the CHEK2 gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families with CHEK2 pathogenic variants in Slovenia.
In the years 2014 to 2019, CHEK2 pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution. Altogether, the study enrolled 75 individuals from 50 CHEK2 families who were carriers of a CHEK2 PV/LPV. The clinical data on 41 BC patients with CHEK2 PV/LPV and other carriers of CHEK2 PV/LPV from Slovenia were collected and analyzed.
Breast cancer was diagnosed in 41 of 75 CHEK2 PV/LPV carriers (40 females, 1 male). The mean age at BC diagnosis was 42.8 years (range, 21-63 years), and 27 (65.8%) of the 41 of patients with BC had a positive family history for BC. Contralateral BC (CBC) was observed in 8 (19.5%) of the 41 patients (mean age, 55.6 years). Of 12 patients with human epidermal growth factor receptor 2 (HER2)-positive tumor type, a c.444+1G > A PV/LPV was detected in 4 patients, c.349A > G in 3 patients, deletion of exons 9-10 in 3 patients, deletion of exon 8 in 1 patient, and c.1427C > T PV/LPV in 1 patient.
Bilateral BC was diagnosed in as many as 19.5% of the Slovenian BC patients with CHEK2 PV/LPVs. Breast cancer associated with a germline CHEK2 PV/LPV occurs in younger patients compared with sporadic BC.
目前，缺乏关于CHEK2基因致病性变异及其对癌症风险影响的数据。本研究旨在探讨斯洛文尼亚携带CHEK2致病性变异的家族中乳腺癌（BC）患者的特征。
2014年至2019年期间，在作者所在机构对50个不同家族的先证者进行基因咨询并使用多基因检测板进行检测，发现了CHEK2致病性变异/可能致病性变异（PV/LPVs）。该研究共纳入了来自50个CHEK2家族的75名个体，他们均为CHEK2 PV/LPV携带者。收集并分析了来自斯洛文尼亚的41例携带CHEK2 PV/LPV的BC患者及其他CHEK2 PV/LPV携带者的临床数据。
75例CHEK2 PV/LPV携带者中有41例被诊断为乳腺癌（40例女性，1例男性）。BC诊断时的平均年龄为42.8岁（范围21 - 63岁），41例BC患者中有27例（65.8%）有BC家族史阳性。41例患者中有8例（19.5%）观察到对侧乳腺癌（CBC）（平均年龄55.6岁）。在12例人表皮生长因子受体2（HER2）阳性肿瘤类型的患者中，4例检测到c.444 + 1G＞A PV/LPV，3例检测到c.349A＞G，3例检测到外显子9 - 10缺失，1例检测到外显子8缺失，1例检测到c.1427C＞T PV/LPV。
在斯洛文尼亚携带CHEK2 PV/LPVs的BC患者中，高达19.5%被诊断为双侧乳腺癌。与散发性BC相比，携带种系CHEK2 PV/LPV的乳腺癌发生在更年轻的患者中。
