Soukupová Jana, Lhotová Klára, Zemánková Petra, Vočka Michal, Janatová Markéta, Stolařová Lenka, Borecká Marianna, Kleiblová Petra, Macháčková Eva, Foretová Lenka, Koudová Monika, Lhota Filip, Tavandzis Spiros, Zikán Michal, Stránecký Viktor, Veselá Kamila, Panczak Aleš, Kotlas Jaroslav, Kleibl Zdeněk
Klin Onkol. 2019 Summer;32(Supplementum2):72-78. doi: 10.14735/amko2019S72.
Ovarian cancer is a disease with high mortality. Approximately 1,000 women are diagnosed with ovarian cancer in the Czech Republic annually. Women harboring a mutation in cancer-predisposing genes face an increased risk of tumor development. Mutations in BRCA1, BRCA2, BRIP1, and Lynch syndrome genes (RAD51C, RAD51D, and STK11) are associated with a high risk of ovarian cancer, and mutations in ATM, CHEK2, NBN, PALB2, and BARD1 appear to increase the risk. Our aim was to examine the frequency of mutations in cancer-predisposing genes in the Czech Republic.
We analyzed 1,057 individuals including ovarian cancer patients and 617 non-cancer controls using CZECANCA panel next-generation sequencing on the Illumina platform. Pathogenic mutations in high-risk genes, including CNVs, were detected in 30.6% of patients. The mutation frequency reached 25.0% and 18.2% in subgroups of unselected ovarian cancer patients and patients with a negative family cancer history, respectively. The most frequently mutated genes were BRCA1 and BRCA2. The overall frequency of mutations in non-BRCA genes was comparable to that in BRCA2. The mutation frequency in ovarian cancer patients aged >70 years was three times higher than that in patients diagnosed before the age of 30.
Ovarian cancer is a heterogeneous disease with a high proportion of hereditary cases. The lack of efficient screening for early diagnosis emphasizes the importance of identifying carriers of mutations in ovarian cancer-predisposing genes; this is because proper follow-up and prevention strategies can reduce overall ovarian cancer-related mortality. This work was supported by grants AZV 15-27695A, SVV2019/260367, PROGRES Q28/LF1. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 7. 3. 2019 Accepted: 24. 4. 2019.
卵巢癌是一种死亡率很高的疾病。在捷克共和国，每年约有1000名女性被诊断出患有卵巢癌。携带癌症易感基因发生突变的女性面临肿瘤发生风险增加。BRCA1、BRCA2、BRIP1以及林奇综合征基因（RAD51C、RAD51D和STK11）的突变与卵巢癌的高风险相关，而ATM、CHEK2、NBN、PALB2和BARD1的突变似乎也会增加风险。我们的目的是研究捷克共和国癌症易感基因的突变频率。
我们使用Illumina平台上的CZECANCA面板二代测序技术，对1057名个体进行了分析，其中包括卵巢癌患者和617名非癌症对照。在30.6%的患者中检测到了高危基因中的致病性突变，包括拷贝数变异（CNV）。在未选择的卵巢癌患者亚组和无家族癌症病史的患者亚组中，突变频率分别达到25.0%和18.2%。突变最频繁的基因是BRCA1和BRCA2。非BRCA基因的总体突变频率与BRCA2相当。70岁以上卵巢癌患者的突变频率比30岁之前诊断出的患者高3倍。
卵巢癌是一种异质性疾病，其中遗传性病例占比很高。缺乏有效的早期诊断筛查凸显了识别卵巢癌易感基因突变携带者的重要性；这是因为适当的随访和预防策略可以降低总体卵巢癌相关死亡率。本研究得到了AZV 15 - 27695A、SVV2019/260367、PROGRES Q28/LF1等基金的支持。作者声明他们在研究中使用的药物、产品或服务方面不存在潜在利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。提交日期：2019年3月7日；接受日期：2019年4月24日。
