癌症易感基因中的致病性或可能致病性种系变异（PGV）可能在肺癌（LC）易感性中发挥作用。然而，确定适合进行基因检测的人群仍不确定。本研究旨在评估选定的肺腺癌患者队列中 PGV 的患病率。进行了一项横断面队列研究，以评估有 LC 家族史、年轻发病、从不/轻度吸烟，或可操作的基因组改变（AGA）。使用 Sophia Hereditary Cancer Solution panel F 进行测序，包括 144 个癌症易感基因。分类为致病性或可能致病性的变异被纳入进一步分析。在 201 名患者中，43 名 (21.4%) 表现出 PGV，其中 64.5% 是 DNA 损伤修复基因，86.1% 具有临床可操作性。主要的 PGV 存在于 ATM (9.3%)、TP53 (6.9%)、BRCA2 (6.9%) 和 CHEK2 (6.9%) 基因中。 PGV 与男性相关（调整后优势比 [aOR] 2.46，95% CI 1.15-5.32，p = 0.021），并且有与 AGA 相关的趋势（aOR 6.04，95% CI 0.77-49.74，p = 0.094）在这项研究中，根据我们的选择标准确定了高 PGV 患病率，这代表了识别种系基因组测试候选者的有效策略、近亲的潜在筛查策略和个性化治疗方式。我们的结果需要在其他人群中进行进一步探索以证实它们。版权所有 © 2024。由 Elsevier B.V. 出版。

Pathogenic or likely pathogenic germline variants (PGVs) in cancer predisposition genes may play a role in lung cancer (LC) susceptibility. However, determining an eligible population for genetic testing remains uncertain. This study aimed to assess the prevalence of PGVs in a selected cohort of individuals with lung adenocarcinoma.A cross-sectional cohort study was conducted to assess the PGVs rate in lung adenocarcinoma patients with a family history of LC, young-onset presentation, history of never/light smoking, or actionable genomic alterations (AGAs). Sequencing was performed using Sophia Hereditary Cancer Solution panel F, including 144 cancer predisposition genes. Variants classified as pathogenic or likely pathogenic were included for further analysis.Of 201 patients, 43 (21.4 %) exhibited PGVs, among which 64.5 % were DNA damage repair genes, and 86.1 % were clinically actionable. The main PGVs were in ATM (9.3 %), TP53 (6.9 %), BRCA2 (6.9 %), and CHEK2 (6.9 %) genes. PGVs were associated with male sex (adjusted odds ratio [aOR] 2.46, 95 % CI 1.15-5.32, p = 0.021), along with a trend toward association with AGAs (aOR 6.04, 95 % CI 0.77-49.74, p = 0.094).In this study, a high PGVs prevalence was identified based on our selection criteria, which represents an effective strategy to identify candidates for germline genomic testing, potential screening strategies in close relatives, and personalized therapeutic modalities. Our results warrant further exploration in other populations to confirm them.Copyright © 2024. Published by Elsevier B.V.