妇科恶性肿瘤筛查中基因检测技术的应用

近年来的研究认为癌症是一种基因疾病,遗传性或获得性基因缺陷可导致癌症的发生和发展。因而,基因检测技术在妇科肿瘤的筛查中显得尤为重要。目前,人乳头瘤病毒（HPV）检测已在宫颈癌筛查中广泛应用,对于遗传性卵巢癌和子宫内膜癌高危群体,也可通过检测BRCA1/2和MLH1/MSH2突变进行高危人群风险分层。     

遗传性妇科肿瘤高风险人群管理专家共识（2020）

1    共识制定背景         遗传性肿瘤综合征系一个或多个基因致病性突变使个体某一器官或多个器官发生肿瘤，且突变基因可在家系中世代遗传，多为常染色体显性遗传，约占全部肿瘤的5%~10%［1］。遗传性肿瘤与癌变通路上癌基因或抑癌基因等的胚系突变相关，根据胚系突变外显情况，可分为完全和不完全外显突变。妇科肿瘤多为不完全外显突变，根据外显率高低可进一步分为高外显率突变、适度外显率突变和低外显率突变［1］。遗传性肿瘤在人群中所占比例不大，但家族肿瘤遗传的易患性对其家庭成员的影响大。遗传性肿瘤的规范咨询有助于筛查和识别高危个体，依据遗传学原则指导干预措施，不仅有利于肿瘤的预防和早期发现，还可参与患者生育决策的选择和后续内分泌治疗。 浏览更多请关注本刊微信公众号及当期杂志。     

遗传性乳腺癌、卵巢癌和子宫内膜癌的预防性手术现状

遗传性乳腺癌、卵巢癌和子宫内膜癌是三种常染色体位点遗传性疾病;表现为遗传性乳腺癌综合征（HBC）,遗传怀乳腺－卵巢癌综合征（HBOC）和遗传性非息肉结直肠癌综合征（HNPCC）。对此具有肿瘤家族遗传倾向的高危人群实施预防性手术可降低肿瘤的发生率,提高预后生存率。     

2022《NCCN遗传性/家族性卵巢癌风险评估与临床管理指南(第1版)》解读

<正>卵巢癌发病率居女性生殖系统恶性肿瘤第3位,死亡率居妇科恶性肿瘤之首[1]。约10%～24%的卵巢癌与特定基因的胚系突变有关[2～5],这种发生在生殖细胞或早期受精卵的基因突变具有家族遗传性[6]。随着遗传学和分子生物学的进步,目前已经发现许多与遗传性卵巢癌相关的基因,携带特定基因突变的人群患卵巢癌的风险明显高出普通人群[2],因此对遗传性卵巢癌高危人群进行癌症风险评估与遗传咨询很有必要。目前遗传性癌症高危人群的基因检测率普遍较低,     

家族性卵巢癌综合征

许多研究表明,部分卵巢癌病例呈家族性传递现象,即家族性或遗传性卵巢癌综合征（familial or hereditary ovarian cancer syndrome,FOCS or HOCS）.属于此类家系的妇女患卵巢癌的机会相当高,对于她们的筛查、诊断、咨询及预防性处理是当前妇科肿瘤领域所关注的重要问题之一.     

遗传性妇科肿瘤人群生育力的保存

<正>遗传性肿瘤综合征是指由于特定致病基因突变导致这些个体患肿瘤的风险明显高于普通人群，具有家族聚集性的肿瘤类型。遗传性肿瘤综合征约占肿瘤的5%～10%[1]。遗传性肿瘤大部分为常染色体显性遗传方式，根据突变外显情况，可分为完全和不完全外显突变。遗传性妇科肿瘤相关的遗传性肿瘤综合征主要包括遗传性乳腺癌-卵巢癌综合征(hereditary breast and ovarian cancer, HBOC)、     

遗传性乳腺癌、卵巢癌和子宫内膜癌的预防性手术现状

遗传性乳腺癌、卵巢癌和子宫内膜癌是三种常染色体位点遗传性疾病:表现为遗传性乳腺癌综合征(HBC),遗传性乳腺-卵巢癌综合征(HBOC)和遗传性非息肉性结直肠癌综合征(HNPCC).对此具有肿瘤家族遗传倾向的高危人群实施预防性手术可降低肿瘤的发生率,提高预后生存率.     

Lynch综合征相关肿瘤概述

Lynch综合征是一种已被公认的遗传性肿瘤综合征,是引起遗传性结直肠癌最常见的病因,也是目前唯一已知的遗传性子宫内膜癌的病因,Lynch综合征相关肿瘤还包括卵巢癌、胃癌、尿路上皮癌和小肠癌等。虽然已明确Lynch综合征的发病机制是错配修复缺陷和微卫星不稳定性,但是近年来其诊断和分子发病机制方面不断有新的进展,提示不同的错配修复基因缺陷对应着不同的Lynch综合征相关肿瘤及不同的发病率,对患者的监测产生着新的影响,治疗手段也在不断丰富和改进,如利用微卫星不稳定性的免疫效应治疗Lynch综合征相关肿瘤已取得了积极的成果。介绍Lynch综合征的遗传学特征、筛查诊断、其相关肿瘤的临床病理特征及治疗,重点阐述该综合征的最新进展。     

细胞色素P450基因多态性与妇科肿瘤易感性

细胞色素P450(CYP)是微粒体混合功能氧化酶中最重要的一族氧化酶,在生物体内分布广泛,CYP参与多种外源性化合物的代谢及内源性物质的生成.同种CYP在人群中可以表现为不同表型,这种遗传多态现象决定了CYP对特定的外来化合物及内源性物质在反应上的差异,即表现为个体对致癌物的不同易感性.就近年来CYP基因、基因多态性的研究现状及CYP1A1、CYP1B1、CYP17和CYP19的多态性与妇科肿瘤易感性的研究进展综述.     

遗传性乳腺癌-卵巢癌综合征

卵巢癌是严重威胁妇女健康的常见恶性肿瘤之一，是妇科恶性肿瘤致妇女死亡的首位疾病。近年来的研究发现，遗传因素是卵巢癌发病最重要的危险因素。有学者将卵巢癌和乳腺癌分为散发性、家族性和遗传性3类。散发性癌多是指在患者的一级或二级亲属中没有乳腺癌或卵巢癌发生；家族性癌是指有2个或以上的一级或二级亲属患有乳腺癌或卵巢癌，但不具有明显的遗传倾向；遗传性癌则是在家族中有卵巢癌或乳腺癌聚发，并符合常染色体遗传特征，多有基因突变。约有5％～7％的乳腺癌以及10％的卵巢癌有遗传倾向。已经确定的3个遗传性卵巢癌综合征包括：遗传性位点特异性卵巢癌综合征，遗传性乳腺癌．卵巢癌综合征（hereditary breast-ovarian cancer syndrome，HBOC）及遗传性非息肉性结直肠癌。其中，以HBOC最常见。HBOC是指一个家族中有2个一级亲属或1个一级亲属和1个二级亲属患乳腺癌或卵巢癌，并具有遗传倾向。了解和研究HBOC在临床上对于发现具有卵巢癌高发风险的人群，并进行严密的观察、咨询、预防、早期诊断和治疗具有重要意义。     

BRCA基因与卵巢癌诊治相关的研究进展

卵巢癌是威胁女性生命健康最常见的恶性肿瘤之一,死亡率居妇科肿瘤之首。乳腺癌易感基因（breast cancer susceptibility gene,BRCA）是重要的肿瘤遗传易感基因,参与调节DNA的损伤修复、细胞生长及凋亡,在维持细胞遗传稳定性方面发挥着不可或缺的作用。BRCA基因突变导致约80%遗传相关性卵巢癌的发生,通过对BRCA基因突变进行筛查检测,能有效评估预测卵巢癌发病风险,干预降低发病率并指导精准治疗。BRCA基因突变存在明显的种族及地域特异性,且显著影响卵巢癌发病率及发病年龄,开展多中心研究、建立相关数据库、制定符合国人的诊治标准是必然趋势。     

Screening for gynaecologic cancers in genetically predisposed women

Hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colon cancer syndrome are the two most important syndromes responsible for inherited cancers in gynaecology. Genetic testing is available for both these syndromes. Breast cancer gene testing is affordable and easy in women with ancestry where the mutation patterns are known, whereas other population groups need full gene screening. Hereditary non-polyposis colon cancer syndrome can now be diagnosed more frequently with the use of immunohistochemistry. Ovarian cancer risk is high in hereditary breast and ovarian cancer syndromes, and advanced screening techniques should be used when preventive surgery is not an option. Early detection techniques offer less protection than prophylactic removal, but enable women to retain their reproductive organs. Oophorectomy has the advantage of reducing breast cancer risk. In colorectal cancer syndromes, the risk for endometrial and ovarian cancer is much elevated. These risks should be recognised and addressed as these diseases are easy to prevent.     

林奇综合征与妇科肿瘤

林奇综合征（Lynch syndrome）又称为遗传性非息肉性结直肠癌综合征（HNPCC）,属于常染色体显性遗传性疾病,是最常见的结直肠癌遗传形式。林奇综合征患者常会患有多种肿瘤,其中子宫内膜癌及卵巢癌与其关系最为密切,可以视为林奇综合征的“前哨”肿瘤。在诊断患有林奇综合征的女性中,其患子宫内膜癌的终生风险（60%）会高于患结直肠癌的风险。结合临床表现标准及肿瘤分子学评估可以对其进行高效的诊断。在林奇综合征的女性患者中,应每1～2年（而不是每年）进行子宫内膜活检,在生育结束后行预防性手术可以起到有效的筛查及预防作用。对林奇综合征及其相关的子宫内膜癌及卵巢癌不断有新的研究进展,主要对林奇综合征的诊断、相关的子宫内膜癌及卵巢癌进行综述。     

林奇综合征相关子宫内膜癌研究进展

林奇综合征（lynch syndrome,LS）是一种常染色体显性遗传病,既往称为遗传性非息肉病性结直肠癌（hereditary nonpolyposis colorectal cancer,HNPCC）,是由DNA错配修复（mismatch repair,MMR）基因MLH1、MSH2、MSH6和PMS2的胚系突变引起。LS患者有多种癌变倾向、发病低龄化及家族易感性,可同时或异时发生结直肠癌、子宫内膜癌（endometrial cancer,EC）、卵巢癌、胃癌和乳腺癌等,女性患者中EC与之最为密切,目前我国对于LS相关EC（LS-EC）认识尚不足,并未形成完整的诊疗标准或指南。为提高对LS-EC的认识,综述LS-EC的分子机制、临床病理特征、筛查及诊断、临床治疗手段、预防等。     

Implications of multigene testing for hereditary breast cancer in primary care

Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a proportion in which a gene mutation can be the cause of the predisposition for breast cancer. A careful assessment of family and clinical history should be performed in these women in order to determine if a genetic counseling referral is indicated. In cases of hereditary breast cancer, genetic testing with a multigene panel can identify specific genetic mutations in over 100 genes. The most common genes mutated in hereditary breast cancer are the high-penetrance BRCA1 and BRCA2 genes. In addition, other mutations in high-penetrance genes in familial cancer syndromes and mutations in DNA repair genes can cause hereditary breast cancer. Mutations in low-penetrance genes and variants of uncertain significance may play a role in breast cancer development, but the magnitude and scope of risk in these cases remain unclear, thus the clinical utility of testing for these mutations is uncertain. In women with high-penetrance genetic mutations or lifetime risk of breast cancer > 20%, risk-reducing interventions, such as intensive screening, surgery, and chemoprevention, can decrease the incidence and mortality of breast cancer.     

遗传性卵巢癌综合征相关易感基因的研究进展

卵巢癌是妇科常见的三大恶性肿瘤之一,病死率居妇科肿瘤的首位。由于缺乏敏感度和特异度高的早期筛查手段,多数患者（60%~65%）诊断时已为晚期。在卵巢癌中遗传性卵巢癌综合征（HOCS）占有一定的比例,HOCS的发生常与易感基因的突变有关。目前至少有16个基因已被确定与HOCS有关,其中乳腺癌易感基因1（BRCA1）和BRCA2的突变与HOCS关系最为密切,而限制性内切酶位点相关DNA（RAD51C）、RAD51D和BRCA1相关的羧基端解旋酶基因1（BRIP1）为近期新发现的与HOCS相关的3个基因,对相关易感基因突变进行检测并对高危人群进行监测可能成为早期卵巢癌诊断的有效手段。综述HOCS相关的易感基因。     

产前筛查高风险的临床认识与干预策略

产前筛查是预防出生缺陷的第2道关键防线,必要的产前常规筛查是杜绝出生缺陷的手段。采用血清学对唐氏综合征妊娠早期筛查和妊娠中期联合筛查,神经管畸形筛查,分子生物技术对地中海贫血的筛查及确诊,产前超声对胎儿体表、内脏器官及骨骼畸形等先天性疾病筛查,从中发现高风险人群。并以生物遗传因素技术为主导,选择适时的产前诊断,提高对胎儿先天性缺陷和遗传性疾病的检出率。加强对高风险人群的质控与管理,对不良妊娠结局提出预见性临床干预及实施新的管理模式,降低出生缺陷,提高人口素质。     

The role of genetic testing for cancer susceptibility in gynecologic practice

Genetic counseling and testing for inherited disorders are part of every obstetrician-gynecologist's practice. Family history, ethnicity, and race are routinely evaluated as a part of the prenatal assessment. The discovery of genes responsible for inherited cancer susceptibility and the wide availability of clinical genetic testing for mutations in these genes have made similar assessments an integral part of gynecologic practice as well. The indications for genetic testing for mutations in BRCA1, BRCA2, and the mismatch repair genes responsible for the hereditary nonpolyposis colon cancer (HNPCC) syndrome need to be individualized. As in obstetrics, genetic counseling can provide critical assessment of the family history to help determine the likelihood of an inherited cancer susceptibility syndrome and the appropriateness of genetic testing. The subsequent clinical recommendations for mutation carriers need to take into account the patient's age, desire for future childbearing, and other medical history when prescribing screening interventions or prophylactic surgery. Practical applications of genetic testing for cancer susceptibility have the ability to reduce the burden of hereditary cancers by saving lives, decreasing medical morbidities, and reducing psychological stress.     

The genetics of uterine leiomyomata: what clinicians need to know

The genetics of many complex diseases, including hypertension, diabetes, and asthma, are receiving intense investigation and beginning to have therapeutic relevance. Family medical history can be a critical source of information for providing optimal patient care. For gynecologists, knowledge of cancer susceptibility genes such as BRCA1 and BRCA2 and the genetic syndrome hereditary nonpolyposis colorectal cancer (Lynch syndrome II) affects how patients are screened for ovarian and endometrial cancers. Similarly, identification of mutations in the fumarate hydratase (FH) gene that lead to a syndrome called hereditary leiomyomatosis and renal cell carcinoma (HLRCC) will impact screening and treatment of women with uterine leiomyomas. Hereditary leiomyomatosis and renal cell carcinoma syndrome is particularly relevant to clinicians and patients because of the resulting increased risk of malignant disease for both the affected woman and her family. The goals of this article are to summarize the evolving genetic information concerning uterine leiomyomas, including hereditary leiomyomatosis and renal cell carcinoma syndrome, and to discuss the clinical importance of these findings. The current role of family medical history and future implications of genes relevant to leiomyoma biology will be reviewed.