Foretová Lenka, Navrátilová Marie, Svoboda Marek, Vašíčková Petra, Sťahlová Eva Hrabincová, Házová Jana, Kleiblová Petra, Kleibl Zdeněk, Macháčková Eva, Palácová Markéta, Petráková Katarína
Klin Onkol. 2019 Summer;32(Supplementum2):6-13. doi: 10.14735/amko2019S6.
An inherited predisposition to breast cancer underlies 5-10% of breast tumors. High-risk BRCA1 and BRCA2 genes result in an 85% lifetime risk of breast cancer and a 20-60% lifetime risk of ovarian cancer. Next-generation sequencing or massive parallel sequencing are now established testing methods that enable screening for many genes that predispose to heterogeneous hereditary cancer syndromes (22 genes are required by the health insurance companies). In addition to BRCA1 and BRCA2, inherited mutations in other genes predispose to breast and/or ovarian cancer. High-risk breast cancer genes include TP53, STK11, CDH1, PTEN, PALB2, and NF1, while moderate-risk (2-4 times increased risk) breast cancer genes include ATM, CHEK2, and NBN. Moderate risk is also suggested for Lynch syndrome, MUTYH, BRIP1, RAD51C, RAD51D, BARD1, FANCA, FANCC, FANCM, BLM, WRN genes. In heterozygotes for other recessive syndromes the risk of developing breast cancer is subject to current research. Low-risk genes are (mostly) irrelevant from a clinical perspective. Other genes that increase the risk of ovarian cancer include the genes for Lynch syndrome, the BRIP1, RAD51C and RAD51D genes. Preventive care should be proposed based on assumed cumulative breast cancer risk (see http: //www.mamo.cz): a risk of >20% for BRCA1/2, TP53, PTEN, STK11, CDH1, PALB2, CHEK2, ATM, and NF1; and a risk of 10-20% for BRIP1, RAD51C, RAD51B, BARD1, FANCA, FANCC, FANCM, NBN, BLM, and WRN. The genetic risk should be assessed by a geneticist and be based on inherited mutations and empirical risk according to family history. Prophylactic mastectomy is considered for high-risk gene carriers but not for moderate-risk gene carriers; however, it may be considered if there is an underlying family history, a risk of parenchyma of the mammary gland, or other risk factors. Ovarian cancer risk increases significantly in carriers of the BRIP1, RAD51C, and RAD51D genes. For prevention of ovarian cancer, prophylactic salpingo-oophorectomy is an important component of preventive care. In ovarian cancer families with no identified risk germline mutation, preventive salpingo-oophorectomy is not routinely recommended but may be considered as the only efficient method of prevention due to the increased empirical risk (4 times) of ovarian cancer in first-degree relatives. Supported by the grant project MH CZ - RVO (MMCI, 00209805), AZV 15-27695A and AZV 16-29959A. 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: 17. 5. 2019 Accepted: 31. 5. 2019.
5% - 10%的乳腺肿瘤存在乳腺癌遗传易感性。高危的BRCA1和BRCA2基因会使患乳腺癌的终生风险达到85%，患卵巢癌的终生风险达到20% - 60%。新一代测序或大规模平行测序现已成为既定的检测方法，可用于筛查许多易导致遗传性癌症综合征异质性的基因（健康保险公司要求检测22种基因）。除了BRCA1和BRCA2，其他基因的遗传性突变也易引发乳腺癌和/或卵巢癌。高危乳腺癌基因包括TP53、STK11、CDH1、PTEN、PALB2和NF1，而中度风险（风险增加2 - 4倍）的乳腺癌基因包括ATM、CHEK2和NBN。林奇综合征、MUTYH、BRIP1、RAD51C、RAD51D、BARD1、FANCA、FANCC、FANCM、BLM、WRN基因也提示存在中度风险。对于其他隐性综合征的杂合子，患乳腺癌的风险目前正在研究中。从临床角度来看，低风险基因（大多）无关紧要。其他增加卵巢癌风险的基因包括林奇综合征相关基因、BRIP1、RAD51C和RAD51D基因。应根据假定的累积乳腺癌风险提出预防性护理建议（见http://www.mamo.cz）：BRCA1/2、TP53、PTEN、STK11、CDH1、PALB2、CHEK2、ATM和NF1的风险>20%；BRIP1、RAD51C、RAD51B、BARD1、FANCA、FANCC、FANCM、NBN、BLM和WRN的风险为10% - 20%。遗传风险应由遗传学家评估，并基于遗传突变和根据家族史得出的经验性风险。对于高危基因携带者可考虑预防性乳房切除术，但中度风险基因携带者不考虑；然而，如果有潜在家族史、乳腺实质风险或其他风险因素，也可考虑。BRIP1、RAD51C和RAD51D基因携带者的卵巢癌风险显著增加。对于卵巢癌预防，预防性输卵管卵巢切除术是预防性护理的重要组成部分。在未发现风险种系突变的卵巢癌家族中，不常规推荐预防性输卵管卵巢切除术，但由于一级亲属中卵巢癌的经验性风险增加（4倍），可将其视为唯一有效的预防方法。由MH CZ - RVO（MMCI，00209805）、AZV 15 - 27695A和AZV 16 - 29959A资助项目支持。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对生物医学论文的推荐。提交日期：2019年5月17日 接受日期：2019年5月31日
