High risk of lung cancer in surfactant-related gene variant carriers,European Respiratory Journal

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High risk of lung cancer in surfactant-related gene variant carriers
European Respiratory Journal ( IF 24.3 ) Pub Date : 2024-05-02 , DOI: 10.1183/13993003.01809-2023
Alexandre Brudon , Marie Legendre , Arthur Mageau , Julien Bermudez , Philippe Bonniaud , Diane Bouvry , Jacques Cadranel , Aurélie Cazes , Bruno Crestani , Tristan Dégot , Céline Delestrain , Rémi Diesler , Ralph Epaud , Quentin Philippot , Nathalie Theou-Anton , Caroline Kannengiesser , Ibrahima Ba , Marie-Pierre Debray , Pascale Fanen , Efrosine Manali , Spyros Papiris , Nadia Nathan , Serge Amselem , Antoine Gondouin , Anne Guillaumot , Claire Andréjak , Stephane Jouneau , Guillaume Beltramo , Yurdagul Uzunhan , François Galodé , Virginie Westeel , Anas Mehdaoui , Sandrine Hirschi , Sylvie Leroy , Sylvain Marchand-Adam , Hilario Nunes , Clément Picard , Grégoire Prevot , Martine Reynaud-Gaubert , Paul De Vuyst , Lidwine Wemeau , Gautier Defossez , Gérard Zalcman , Vincent Cottin , Raphael Borie ,

Background

Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers.

Methods

We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers.

Results

We identified 99 SRG adult variant carriers (SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer (SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01–1.08), smoking (OR 20.7, 95% CI 6.60–76.2) and SFTPA1/SFTPA2 variants (OR 3.97, 95% CI 1.39–13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1–44.7).

Conclusions

The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.

中文翻译：

表面活性剂相关基因变异携带者肺癌风险高

背景

一些与间质性肺病相关的罕见表面活性剂相关基因 (SRG) 变异被怀疑与肺癌相关，但数据缺失。我们的目的是研究国际 SRG 变异携带者队列中肺癌的流行病学和表型。

方法

我们对 OrphaLung 网络中所有携带 SRG 变异的成年人进行了一项横断面研究，并将端粒相关基因 (TRG) 变异携带者的肺癌风险进行了比较。

结果

我们鉴定了 99 名 SRG 成人变异携带者（SFTPA1 (n=18)、SFTPA2 (n=31)、SFTPC (n=24)、ABCA3 (n=14) 和NKX2-1 (n=12)），其中 20 名 (20.2 %) 患有肺癌（SFTPA1 (n=7)、SFTPA2 (n=8)、SFTPC (n=3)、NKX2-1 (n=2) 和ABCA3 (n=0)）。在 SRG 变异携带者中，患肺癌的几率与年龄（OR 1.04，95% CI 1.01–1.08）、吸烟（OR 20.7，95% CI 6.60–76.2）和SFTPA1 / SFTPA2变异（OR 3.97，95% CI 1.39–13.2）。腺癌是唯一报道的组织学类型，三个样本中肿瘤细胞中程序性死亡配体-1 表达≥1%。 8 名 (40%) 个体的癌症分期为局部 (I/II)，2 名 (10%) 个体为局部晚期 (III)，10 名 (50%) 个体为转移性 (IV)。我们发现没有适合靶向治疗的体细胞变异。 7 例癌症被手术切除，10 例接受全身治疗，3 例根据其阶段和表现状态接受最佳支持治疗。中位总生存期为 24 个月，I/II 期癌症显示出更好的生存期。我们确定了 233 个 TRG 变异携带者。 SRG 患者与TRG 患者的肺癌相对风险（亚分布风险比）为 18.1 (95% CI 7.1–44.7)。