1635P - Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic ductal adenocarcinoma patients

Background

Assessment of germline BRCA1-2 pathogenic variants (gPV) is routinely recommended in Pancreatic Ductal Adenocarcinoma (PDAC) patients (pts), due to clinical-epidemiological relevance. Limited data are available on the prevalence of gPV in other cancer predisposition genes, including the DNA Damage Response (DDR) system.

Methods

Clinical data of consecutive PDAC pts, of any age and stage, tested with a multigene germline panel between January 2018 and March 2023 in five Italian Institutes were collected. A descriptive analysis of gPV (class 4 and 5) frequency, clinical variables and risk factors, was performed. Since gene panels did not overlap across all Institutes, it was difficult to properly estimate the real prevalence of gPV and to compare the clinical characteristics of all wild type with any-PV population, as screened pts/gene also varied (291-1200). Herein we report the best scenario that may result in rates underestimation.

Results

Among the 1200 pts included in the analysis, 169 (14%) had a gPV (any-PV). 23/73 genes had a gPV in ≥ 1 patient. Genes with a gPV in >1% of tested pts were ATM (36/1200 - 3.0%), BRCA2 (35/1200 - 2.9%), CDKN2A (23/942 - 2.4%), BRCA1 (18/1200 - 1.5%), CHEK2 (11/838 - 1.3%), and COL7A1 (5/447 - 1.1%). Characteristics of the main cohorts are shown in the table. The risk of having a genomic gPV was ≥9% in all the subgroups of pts considered for the different variables, including >73 years old pts (11%). Moreover, 25% of pts with age 41-50, 18% of obese pts and 21% of pts with PDAC/breast/ovarian/prostate cancer/melanoma family history harbored a gPV.

Table: 1635P

Patients’ characteristics [N (%)]

NA: not available

Conclusions

Our study highlighted a remarkable prevalence of gPV in cancer predisposition and DDR genes in a large cohort of PDAC pts. These findings endorse the implementation of an extended multigene germline panel to be offered to all PDAC pts, irrespective of age, stage, and personal/family history.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

M. Reni.

Funding

Has not received any funding.

Disclosure

G. Giordano: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bayer; Financial Interests, Personal and Institutional, Financially compensated role: Servier, Amgen, Seagen, Novartis, Ipsen. M. Reni: Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly, Panavance, Celgene, AstraZeneca, Viatris, Merck Sharp & Dohme, Servier, Sotio, Baxter; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.