Abstract 24P
Background
Almost 15% of NSCLCs are not attributable to smoking risk factor and genetic predisposition to this disease has not been broadly studied, especially in non-Asian population. INHERITY LC is a multicentric cohort aiming to explore germline mutations in patients with NSCLC and elucidate the role of hereditary as risk factor for NSCLC. We present the first exploratory data.
Methods
Using a 61-gene panel next generation sequencing (NGS) we explore the presence of germline mutations in a cohort of 54 Spanish patients with NSCLC. Blood samples were collected from May 2021 to February 2022. Selection criteria were: 1) familiar history of lung cancer (first-degree relative or two or more second-degree relatives with NSCLC) 2) age criteria and negative or low tobacco exposure (diagnose < 45 years or < 60 years with < 15 packs-year index) 3) presence of somatic actionable mutations in the tumor biopsy.
Results
Median age was 57 years; 23 male (43%), 31 female (57%); 46 adenocarcinoma (85%), 7 squamous (13%); 51 Caucasian (94%); 21 patients with first-degree relative (39%), 4 with two or more second-degree relatives (7%); 28 somatic actionable mutations (52%): 16 in EGFR (29%), 10 in ALK (18%), 2 in ROS-1 (4%). Germline variants were identified in 18 patients (33,3%). 4 of them pathogenic or likely pathogenic variants (7,5%): 1 pathogenic mutation in BRCA2; 3 variants likely-pathogenic (VLP) were found in XRCC2, BRIP1 and NBN genes. Variants of uncertain significance (VUS) were described in 14 patients in BRF1, POLD1, BRCA2, ATM, MRE11, CDH1, POLE, MSH2, PDGFRA, KIT, MLH1 and APC genes. ATM and BRCA2 were the most common reported genes on this series. Germline variants were identified in 33% of patients with a first-degree relative with NSCLC, in 32% of patients with somaticactionable mutations and in 18% of patients with diagnose of lung cancer under 45 years.
Conclusions
One third of patients with lung cancer family aggregation, absence of tobacco exposure, young age at diagnosis or presence of actionable mutations may have germline variants in genes involved in DNA repair mechanisms, which could have a role in NSCLC hereditary predisposition. INHERITY LC is ongoing and final results with a larger sample and multivariable studies are underway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Asociación para la Investigación del Cáncer de Pulmón En Mujeres (ICAPEM).
Funding
ICAPEM.
Disclosure
All authors have declared no conflicts of interest.