Abstract 190P
Background
The role of genetic susceptibility in familial aggregation of non-small cell lung cancer (NSCLC) is understudied and standard guidelines for hereditary testing are unavailable. In this study, we report the prevalence of pathogenic/ likely-pathogenic (P/LP) germline variants in NSCLC patients with family history of cancer.
Methods
We screened 570 Indian NSCLC patients for family history of malignancy and recruited 78 patients with at least one affected first-degree relative or two affected second-degree relatives. Following informed consent and pretest genetic counselling, patients were prospectively tested using an NGS panel of 143 cancer predisposition genes (80-100x coverage). Patients with P/LP germline variants were referred for genetic counselling, and when possible one of their unaffected first-degree family members was tested.
Results
In our cohort of 78 patients with family history of cancer, we found that 13 patients (17%) harboured P/LP germline variants in the following cancer predisposition genes: BRCA1 (n = 1), BRCA2 (n = 2), CHEK2 (n = 1), ATM (n = 2), BAP1 (n = 1), FANCA (n = 1), FANCI (n = 1), FANCM (n = 1), LZTR1 (n = 2), and XRCC3 (n = 1). The majority of the patients were male, had adenocarcinoma histology and stage IV disease. There were no statistically significant differences in clinicopathological features between patients with or without P/LP variants. The most common malignancies reported in the patients’ relatives were head and neck cancers (n = 20, 26%), lung cancer (n = 11, 14%) and breast cancer (n =10, 13%). Table: 190P
| P/LP variant positive (n = 13) | P/LP variant negative (n = 65) | P-value | |
| Age, median (range) | 60 (47-73) | 58 (21-79) | 0.615 |
| Gender, n (%) | |||
| Male | 9 (69%) | 42 (65%) | 0.999 |
| Female | 4 (31%) | 23 (35%) | |
| Smoking Status, n (%) | |||
| Smoker | 7 (54%) | 28 (43%) | 0.476 |
| Non-smoker | 6 (46%) | 37 (57%) | |
| Histology, n (%) | |||
| Adenocarcinoma | 9 (69%) | 54 (83%) | 0.459 |
| Non-adenocarcinoma | 4 (31%) | 11 (17%) | |
| Driver Mutations (EGFR, ALK, ROS1), n (%) | |||
| Positive | 4 (31%) | 23 (35%) | 0.999 |
| Negative / Not tested | 9 (69%) | 42 (65%) | |
| Stage, n (%) | |||
| I - III | 3 (23%) | 16 (25%) | 0.901 |
| IV | 10 (77%) | 49 (75%) |
Conclusions
In this cohort, 17% of NSCLC patients with a family history of cancer harboured P/LP germline variants. Larger studies including diverse ethnicities and familial aggregation are warranted to understand the role of genetic susceptibility and make generalised recommendations for germline testing in patients with NSCLC.
Legal entity responsible for the study
The authors.
Funding
Institutional Research Grant by Lady Tata Memorial Trust.
Disclosure
All authors have declared no conflicts of interest.