P40 Analysis of Family Clustering in Lung Cancer (LC): Genetic Cancer Risk Assessment (GRCA) into the Thoracic Oncology Unit

Abstract

Inherited susceptibility for lung cancer (LC) has been described, a recent paper showed that 2.5% of LC patients (pts) carried a pathogenic germline variation in genes such ATM, TP53, BRCA2, EGFR, and PARK2. Some of those genes cause well recognized syndromes. Thus, GRCA for LC could help to identify a genetic predisposition syndrome, guide genetic testing, offering specific treatments and genetic counseling. This is a retrospective and descriptive study. We performed a review of 66 medical records of LC pts diagnosed between 2011 and 2016. We collected age at diagnosis, smoking, previous cancer diagnosis, and family history (FH) for cancer: number of affected family members and sort of cancer. Genetic evaluation and testing was not available at time of first evaluation, but we tried to identify genetic syndromes according to the clustering pattern and NCCN criteria. Mean age was 62.5 years (range 26-88y); 30 pts (45.5%) had FH with 46 affected relatives: 21 pts had at least one first degree affected member, only 2 pts had more than 3 affected members. Among the tumors, Breast cancer (BrCa) was found in 12 family members; one pt had a previous BrCa diagnosis at 33y; LC was found in 1 relative; 4 cases of colon cancer were described; 1 case was found for prostate and melanoma respectively. Other tumors were described, but they are not frequently associated to other genetic syndromes. We found no statistical differences on smoking between pts with or without FH. Pts with FH tended to be younger (p=0.026). Based on the family assessment, 8 (10.6%) cases met NCCN criteria for genetic counseling and testing for BRCA and Homologous Recombination (HR) pathway genes. Unfortunately, age of diagnosis for family members was available in 8 out 46 cases, data available were taken from the first clinical assessment which limits this analysis. Even if the expected number of pts with inherited susceptibility to LC is low, a proper GRCA could improve the diagnosis of genetic syndromes. This could bring advantages, such as offering PARP inhibitors for Pts carrying mutations in HR pathway genes, cascade screening and set up prevention measures adapted for each gene risks. Finally, more extended genetic analysis could be offered based on clinical features of index cases. At our knowledge, GRCA clinics for LC is not frequent in Mexico, these results underline the importance of setting up this clinic at our center.