Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for
response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence
among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic
heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients.
Materials and methods: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis
for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our
analysis, breast, ovarian, pancreas, and prostate cancer in a patient’s family history was considered as potentially BRCAassociated. Patients or disease characteristics were examined using the c2 test or Fisher’s exact test for qualitative
variables and the Student's t-test or ManneWhitney test for continuous variables, as appropriate.
Results: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median
age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated
cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/
gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years,
P ¼ 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old,
9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years
old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients
with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations.
Conclusion: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients
with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage,
due to the therapeutic implications and cancer risk prevention in patients' relatives.
Key words: germline BRCA, epidemiology, pancreatic cancer genetics, familial cance