Author of

• 34914

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  FP01 - Early Stage/Localized Disease (ID 111)

  • Event: WCLC 2020
  • Type: Posters (Featured)
  • Track: Early Stage/Localized Disease
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 34918

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    FP01.03 - Genetic Predisposition for Pre-Invasive Lung Adenocarcinoma Manifesting as Ground-Glass Nodules with Family History of Lung Cancer (ID 1512)

    00:00 - 00:00  |  Author(s): Zai-Xian Tai
    • Abstract
    • Slides

    Introduction
    

    Lung cancer with family history have been increasing gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The predisposition of GGN with lung cancer family history remains baffling.

    Methods
    

    This prospective study (NCT04220268) enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, which presenting as GGN in computer tomography (CT) scans. We used extreme phenotype approach to select 50 GGN patients with a family history of lung cancer (FHLC) in one or more first-degree relatives. Blood samples were collected and sequenced by whole exome sequencing (WES) to investigate rare but potential pathogenic germline mutations with a stepwise filtering strategy including: variant quality and classification, minor allele frequency (MAF) < 0.01 in public and local database, functional prediction and family segregation.

    Results
    

    In total, 2325 single nucleotide variants (SNVs) and 238 frameshift mutations with MAF <0.01 were finally identified through the filter. The number of these rare, damaging germline mutations in non-smoking patients were significantly higher than those in smoking patients (Spearman’s ρ= -0.33, p=0.02). Fifty-nine SNVs and 10 frameshifts were not only rare and deleterious but also presented in more than two families. Importantly, twenty of them had been reported to be associated with higher risk or carcinogenesis of lung cancer. Two of them were validated in 126 nonoverlapping susceptibility loci for lung carcinogenesis identified by genome-wide association studies (GWAS).

    Conclusion
    

    Patients with GGNs and FHLC may have inheritable carcinogenesis mutations. These variants may potentially contribute to the risk of pulmonary pre-invasive adenocarcinoma susceptibility in Chinese population. Non-smoking patients with GGN probably had higher genetic predisposition than the smoking patients.

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