Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：癌症易感性基因中的致病性或可能致病性种系变异体（PGV）可能在肺癌（LC）易感性中起作用。然而,确定基因检测的合格人群仍不确定。本研究旨在评估一组选定的肺腺癌患者中PGV的患病率。
方法：进行了一项横断面队列研究，以评估具有LC家族史的肺腺癌患者的PGV率。年轻的发病介绍，从不/轻度吸烟的历史，或可操作的基因组改变(AGA)。使用Sophia遗传性癌症解决方案F组进行测序，包括144个癌症易感基因。包括分类为致病性或可能致病性的变体用于进一步分析。
结果：在201例患者中，43（21.4%）表现出PGV，其中64.5%是DNA损伤修复基因，86.1%是临床可行的。主要的PGV在ATM（9.3％），TP53（6.9%），BRCA2（6.9%），和CHEK2（6.9%）基因。PGV与男性相关(调整后比值比[aOR]2.46,95%CI1.15-5.32,p=0.021),以及与AGA相关的趋势(aOR6.04，95%CI0.77-49.74，p=0.094)。
结论：在这项研究中，根据我们的选择标准确定了高PGV患病率，这代表了一种有效的策略来确定种系基因组测试的候选者，近亲的潜在筛查策略，和个性化的治疗方式。我们的结果值得在其他人群中进一步探索以证实它们。
方法：进行了一项横断面队列研究，以评估具有LC家族史的肺腺癌患者的PGV率。年轻的发病介绍，从不/轻度吸烟的历史，或可操作的基因组改变(AGA)。使用Sophia遗传性癌症解决方案F组进行测序，包括144个癌症易感基因。包括分类为致病性或可能致病性的变体用于进一步分析。
结果：在201例患者中，43（21.4%）表现出PGV，其中64.5%是DNA损伤修复基因，86.1%是临床可行的。主要的PGV在ATM（9.3％），TP53（6.9%），BRCA2（6.9%），和CHEK2（6.9%）基因。PGV与男性相关(调整后比值比[aOR]2.46,95%CI1.15-5.32,p=0.021),以及与AGA相关的趋势(aOR6.04，95%CI0.77-49.74，p=0.094)。
结论：在这项研究中，根据我们的选择标准确定了高PGV患病率，这代表了一种有效的策略来确定种系基因组测试的候选者，近亲的潜在筛查策略，和个性化的治疗方式。我们的结果值得在其他人群中进一步探索以证实它们。
