114P - Prevalence and landscape of pathogenic or likely pathogenic germline variants in cancer predisposition genes among selected patients with lung adenocarcinoma

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 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

We incluided 201 patients, of which 43 (21.4%) exhibited PGVs, identifying that 64.5% occurred in DNA damage repair genes, being 86.1% clinically actionable. The most frequent PGVs were found 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] 2.54, 95% CI 1.17–5.53, p=0.019), very young-onset presentation (aOR 5.79, 95% CI 1.35–24.74, p=0.018), and first-degree relatives with LC (aOR 3.78, 95% CI 1.11–12.83, p=0.033), along with a trend toward association with AGAs (aOR 6.42, 95% CI 0.79–52.18, p=0.082).

Conclusions

This study identified a high PGVs prevalence based on our selection criteria, thus representing an effective strategy to select 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.

Clinical trial identification

NCT06181812.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was supported by CONAHCyT (A3-S-47960) and Becas Impulso a La Investigación En Salud “Carlos Slim” 2023 (N20230149).

Disclosure

All authors have declared no conflicts of interest.