CDH1 pathogenic variants and cancer risk in an unselected patient population.
CDH1 pathogenic variants and cancer risk in an unselected patient population.
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DOI：
10.1007/s10689-021-00257-x
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发表时间：
2022-04
期刊：
影响因子：
2.2
通讯作者：
Abul-Husn NS
中科院分区：
文献类型：
--
作者：
Bar-Mashiah A;Soper ER;Cullina S;Belbin GM;Kenny EE;Lucas AL;Abul-Husn NS
CDH 1致病性变体赋予发展弥漫性胃癌（DGC）和小叶乳腺癌（LBC）的显著升高的终生风险。本研究的目的是评估CDH 1致病性变异体在家族和祖先多样性BioMe生物库中的患病率和临床影响。我们评估了来自30，223名成人BioMe参与者的外显子组序列数据，以识别CDH 1阳性个体，定义为那些携带先前归类为致病性或可能致病性（P/LP）的变体或预测的CDH 1功能丧失变体的个体。我们回顾了电子健康记录和BioMe登记调查的个人和家族恶性肿瘤史以及既往临床基因检测的证据。使用基因组学优先的方法，我们在BioMe中鉴定了6个CDH 1阳性个体（约1/5，000）。CDH 1阳性个体的中位年龄为42岁（范围为35至62岁），所有人均为自我报告的非欧洲人，1人为女性。没有证据表明DGC或LBC的个人或家族史。我们的研究结果表明，在CDH 1中携带致病性变异体的AML患者中，DGC和LBC的风险较低。在没有个人或家族史的个体中了解CDH 1相关癌症风险可能更好地为监测和预防措施提供信息。
CDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact of CDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identify CDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic (P/LP) or a predicted loss-of-function variant in CDH1. We reviewed electronic health records and BioMe enrollment surveys for personal and family history of malignancy and evidence of prior clinical genetic testing. Using a genomics-first approach, we identified 6 CDH1 positive individuals in BioMe (~1 in 5,000). CDH1 positive individuals had a median age of 42 years (range 35 to 62 years), all were non-European by self-report, and one was female. None had evidence of either a personal or family history of DGC or LBC. Our findings suggest a low risk of DGC and LBC in unselected patients harboring a pathogenic variant in CDH1. Knowledge of CDH1-related cancer risk in individuals with no personal or family history may better inform surveillance and prophylactic measures.
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影响因子：
4
作者：
van der Post RS;Vogelaar IP;Carneiro F;Guilford P;Huntsman D;Hoogerbrugge N;Caldas C;Schreiber KE;Hardwick RH;Ausems MG;Bardram L;Benusiglio PR;Bisseling TM;Blair V;Bleiker E;Boussioutas A;Cats A;Coit D;DeGregorio L;Figueiredo J;Ford JM;Heijkoop E;Hermens R;Humar B;Kaurah P;Keller G;Lai J;Ligtenberg MJ;O'Donovan M;Oliveira C;Pinheiro H;Ragunath K;Rasenberg E;Richardson S;Roviello F;Schackert H;Seruca R;Taylor A;Ter Huurne A;Tischkowitz M;Joe ST;van Dijck B;van Grieken NC;van Hillegersberg R;van Sandick JW;Vehof R;van Krieken JH;Fitzgerald RC
通讯作者：
Fitzgerald RC
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
8.8
作者：
Kalia, Sarah S.;Adelman, Kathy;Miller, David T.
通讯作者：
Miller, David T.
影响因子：
10.3
作者：
Katona, Bryson W.;Clark, Dana Farengo;Domchek, Susan M.
通讯作者：
Domchek, Susan M.
影响因子：
12.3
作者：
Abul-Husn, Noura S.;Soper, Emily R.;Kenny, Eimear E.
通讯作者：
Kenny, Eimear E.