Abstract 363P
Background
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 genome predisposition of GGNs with lung cancer family history remains baffling.
Methods
This prospective study (NCT04220268) enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, which presenting as GGNs in computer tomography (CT) scans. We collected blood and tumor samples from 59 patients with GGNs and first-degree relative family history of lung cancer (FHLC) to investigated germline and somatic mutations by whole exome sequencing (WES). Pre-invasive neoplasia causal variants were detected by quality, classification, minor allele frequency (MAF), functional prediction, and family segregation filter. Validation was conducted in an external cohort of 669 healthy participants without cancer, and in 126 nonoverlapping susceptibility loci for lung carcinogenesis identified by recent genome-wide association studies (GWAS).
Results
Eighty-five single nucleotide variants (SNVs) and 11 frameshifts were detected, which were rare, predicted as damaging, and presented in more than two families. Fifteen of them had been reported that were associated with high risk of lung cancer or deleterious function. The MAF of them were lower than 0.01 in a local health Asian cohort and human exome databases. Three of them were validated in 126 susceptibility loci for lung carcinogenesis. The number of the rare, damaging and repeatedly germline mutations in non-smoking patients were significantly higher than those in smoking patients (2436 vs 593, p<0.05). The number of these germline mutation showed no significant difference between the patients with pure GGNs and mixed GGNs (1298 vs 1333, p>0.05).
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine (Grant No. 2017B030314120), National Natural Science Foundation of China (Grant No. 81673031&No. 81872510), High-level Hospital Construction Project (DFJH201801), Guangdong Provincial People's Hospital Young Talent Project (No. GDPPHYTP201902).
Disclosure
R-R. Chen, Z-X. Tai, H-X. Lin: Full/Part-time employment: GenePlus-Beijing Institute, Beijing, China. All other authors have declared no conflicts of interest.
Resources from the same session
424P - Hippocampus sparing in volumetric modulated arc therapy (VMAT) for brain tumour radiotherapy treatment
Presenter: Eva Yi Wah Cheung
Session: e-Poster Display Session
425P - The impact of obesity on treatment outcomes in patients with solid tumour malignancies treated with first-line (1L) immuno-oncology (IO) agents
Presenter: Chun Loo Gan
Session: e-Poster Display Session
426P - A multicenter, randomized, double-blind, phase II study of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) to evaluate the safety and efficacy of a daily oral starting dose of 18 mg vs 24 mg
Presenter: Marcia S. Brose
Session: e-Poster Display Session
427P - On the clinical implications of systemic and local immune responses in human angiosarcoma
Presenter: Jason Yongsheng Chan
Session: e-Poster Display Session
428P - Prognostic value of clinico-pathological characteristics and peripheral monocyte counts in localised extra-meningeal solitary fibrous tumours treated with surgical resection
Presenter: Ryan Lim
Session: e-Poster Display Session
429P - Demographics, pattern of care, and outcome analysis of malignant melanoma cases from a tertiary care centre in India
Presenter: Anshul Agarwal
Session: e-Poster Display Session
430P - Teenagers and young adult cancers in rural central India: Access to age-appropriate care
Presenter: Runu Sharma
Session: e-Poster Display Session
431P - Quantitative study of two critical lncRNAs in patients with glioma tumours
Presenter: Kamal Mohammadian
Session: e-Poster Display Session
432P - Efficacy and tolerability of vismodegib treatment in locally advanced and metastatic basal cell carcinoma
Presenter: Mustafa Gürbüz
Session: e-Poster Display Session
433P - Association between aspirin and cancer risk: A Mendelian randomization analysis
Presenter: Yu Jiang
Session: e-Poster Display Session