CLINICOPATHOLOGIC FEATURES AND MUTATIONAL SPECTRUM IN BRAZILIAN PATIENTS WITH EARLY ONSET PANCREATIC CANCER

Introduction: Besides the dismal prognosis, pancreatic cancer may become the second leading cause of cancer death by 2030. Pancreatic cancer in young adults is not frequent and more studies are needed to understand the causes and behavior of the disease in this age group. Our aim was to characterize family history, habits and germline mutations in cancer predisposing genes in a Brazilian cohort of young patients (defined as ≤50 years). Methods: Patients with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of stage of the disease or family history. These patients answered a questionnaire of life habits and family history of cancer and the genomic DNA was obtained from peripheral blood for Next Generation Sequencing using the TruSight Hereditary Cancer panel, comprising 113 cancer predisposing genes, on the MiSeq platform. Results: 137 patients were included in the 2018-2020 period; 22 (16%) are early onset pancreatic cancer with mean age of 44 years (27-50), comprising 14 women and 8 men. Among early onset pancreatic cancer (≤50 years), only 4 patients (18%) reported cancer in first-degree relatives. Regarding risk factors, 10 patients (45%) reported smoking; 5 (23%) alcohol ingestion; 6 (27%) obesity and only 2 (9%) reported regular physical activity. Fifteen patients (68%) were diagnosed with T4 or metastatic disease. To date, genomic DNA from 10 early onset pancreatic cancer was sequenced and found two patients were carriers of pathogenic germline variants, one in CHEK2 and one in FANCM. Another three patients were carriers of variants of uncertain significance (VUS) in BRCA2, ATM and RAD50. Conclusion: In this unselected group of pancreatic cancer patients, the proportion of early onset pancreatic cancer was 16% (apparently higher than in previous studies). Among young patients, almost 70% were diagnosed with advanced disease, and the main risk factors, reported by almost half of the patients, was smoking. Family history was reported by 20% and to the present date, pathogenic mutations were detected in CHEK2 and FANCM. Future analyzes will allow a better understanding of the mutational profile in these young patients, mainly in the multiethnic Brazilian population.