Rosenblum Rachel E, Ang Celina, Suckiel Sabrina A, Soper Emily R, Sigireddi Meenakshi R, Cullina Sinead, Belbin Gillian M, Lucas Aimee L, Kenny Eimear E, Abul-Husn Noura S
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
JCO Precis Oncol. 2020 Nov 23;4. doi: 10.1200/PO.20.00290. eCollection 2020.
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 Bio Biobank in New York City.
Exome sequence data from 30,223 adult Bio participants were evaluated for pathogenic, likely pathogenic, and predicted loss-of-function variants in , , , and . Survey and electronic health record data from variant-positive individuals were reviewed for personal and family cancer histories.
We identified 70 individuals (0.2%) harboring LS-associated variants in (n = 12; 17%), (n = 13; 19%), (n = 16; 23%), and (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 variants (31%) and lowest in those with variants (7%). LS-associated variants were associated with increased risk of colorectal (odds ratio [OR], 5.0; = .02) and endometrial (OR, 30.1; = 8.5 × 10) cancers in Bio Only 2 variant-positive individuals (3%) had a documented diagnosis of LS.
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.
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及临床影响的数据有限。我们在纽约市具有多样祖先背景的生物样本库中识别并描述了携带LS相关变异的个体。
对来自30223名成年生物样本库参与者的外显子序列数据进行评估，以查找在 、 、 及 基因中的致病、可能致病和预测功能丧失变异。对变异阳性个体的调查及电子健康记录数据进行回顾，以了解个人及家族癌症病史。
我们识别出70名个体（0.2%）在 基因（n = 12；17%）、 基因（n = 13；19%）、 基因（n = 16；23%）和 基因（n = 29；41%）中携带LS相关变异。总体患病率为1/432，自我报告为非洲血统的个体患病率（1/299）高于西班牙裔/拉丁裔（1/654）或欧洲血统（1/518）个体。13名变异阳性个体（19%）有个人LS相关癌症病史，19名（27%）有家族LS相关癌症病史。携带 基因变异的个体中LS相关癌症发生率最高（31%），而携带 基因变异的个体中最低（7%）。在生物样本库中，LS相关变异与结直肠癌（优势比[OR]，5.0； = 0.02）和子宫内膜癌（OR，30.1； = 8.5×10）风险增加相关。仅2名变异阳性个体（3%）有记录在案的LS诊断。
我们发现纽约市非洲血统个体中LS相关变异的患病率更高。虽然变异阳性个体的癌症风险显著增加，但大多数人并未得到LS的临床诊断，提示该病未得到充分认识。
