Lynch Syndrome-Associated Variants and Cancer Rates in an Ancestrally Diverse Biobank.
Lynch Syndrome-Associated Variants and Cancer Rates in an Ancestrally Diverse Biobank.
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DOI：
10.1200/po.20.00290
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发表时间：
2020-01-01
影响因子：
4.6
通讯作者：
Abul-Husn, Noura S
中科院分区：
文献类型：
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作者：
Rosenblum, Rachel E;Ang, Celina;Abul-Husn, Noura S
目得：关于林奇综合征（LS）相关基因组变异在非欧洲血统人群中的患病率和临床影响的数据有限。我们在纽约市的BioMe Biobank中鉴定并鉴定了具有LS相关变异体的个体，患者和方法：对来自30,223名成年BioMe参与者的外显子序列数据进行了致病性、可能致病性和预测MLH 1、MSH 2、MSH 6和PMS 2功能丧失变异体的评价。调查和电子健康记录数据从变异阳性的个人进行了审查，为个人和家族cancerhistory.RESULTS：我们确定了70个人（0.2%）窝藏LS相关的变异MLH 1（n = 12; 17%），MSH 2（n = 13; 19%），MSH 6（n = 16; 23%），和PMS 2（n = 29; 41%）。总体患病率为1/432，自我报告的非洲血统个体的患病率（1/299）高于西班牙裔/拉丁裔（1/654）或欧洲血统（1/518）。13名变异阳性个体（19%）有个人病史，19名（27%）有LS相关癌症的家族史。LS相关的癌症发生率在MSH 6变异体中最高（31%），在PMS 2变异体中最低（7%）。在BioMe中，LS相关变异与结直肠癌（比值比[OR]，5.0; P = 0.02）和子宫内膜癌（OR，30.1; P = 8.5 * 10-9）风险增加相关。只有2个变异阳性的个人（3%）有记录的诊断LS。结论：我们发现一个较高的患病率LS相关的变异个体之间的非洲血统在纽约市。虽然癌症的风险显着增加变异阳性个体，大多数没有窝藏LS的临床诊断，这表明对这种疾病的认识不足。
PURPOSE: Limited data are available on the prevalence and clinical impact of Lynch syndrome (LS)-associated genomic variants in non-European ancestry populations. We identified and characterized individuals harboring LS-associated variants in the ancestrally diverse BioMe Biobank in New York City.PATIENTS AND METHODS: Exome sequence data from 30,223 adult BioMe participants were evaluated for pathogenic, likely pathogenic, and predicted loss-of-function variants in MLH1, MSH2, MSH6, and PMS2. Survey and electronic health record data from variant-positive individuals were reviewed for personal and family cancer histories.RESULTS: We identified 70 individuals (0.2%) harboring LS-associated variants in MLH1 (n = 12; 17%), MSH2 (n = 13; 19%), MSH6 (n = 16; 23%), and PMS2 (n = 29; 41%). The overall prevalence was 1 in 432, with higher prevalence among individuals of self-reported African ancestry (1 in 299) than among Hispanic/Latinx (1 in 654) or European (1 in 518) ancestries. Thirteen variant-positive individuals (19%) had a personal history, and 19 (27%) had a family history of an LS-related cancer. LS-related cancer rates were highest in individuals with MSH6 variants (31%) and lowest in those with PMS2 variants (7%). LS-associated variants were associated with increased risk of colorectal (odds ratio [OR], 5.0; P = .02) and endometrial (OR, 30.1; P = 8.5 * 10-9) cancers in BioMe. Only 2 variant-positive individuals (3%) had a documented diagnosis of LS.CONCLUSION: We found a higher prevalence of LS-associated variants among individuals of African ancestry in New York City. Although cancer risk is significantly increased among variant-positive individuals, the majority do not harbor a clinical diagnosis of LS, suggesting underrecognition of this disease.