Genetic Variants in Patients With a Family History of Pancreatic Cancer

Abstract

Objectives: Up to 15% of pancreatic cancer is hereditary. We aim to study the prevalence of pathogenic germline variants (PGVs) in patients referred for genetic counseling with a family history (FH) of pancreatic cancer. Methods:We performed a retrospective single institution cohort study of individuals who underwent cancer genetic counseling with a FH of pancreatic cancer. Results:We identified 314 patients. Genetic testing was performed in 291 (92.7%) and 187 (59.6%) underwent expanded multigene panel testing. Fifty-four PGVs were found in 53 (16.9%) individuals; PGVs in BRCA1/2 (37%) were most common. Seventy-two variants of uncertain significance (VUS) were found in 58 (18.5%) individuals; VUS in ATM (16.7%) were the most common. Of the 112 (35.4%) with a first-degree family member with pancreatic cancer, 14 PGVs were identified in 14 (12.5%) individuals and 28 VUS were identified in 21 (18.8%) individuals. After genetic testing, 47 (15.0%) individuals met International Cancer of the Pancreas Screening criteria and 67 (21.3%) met American College of Gastroenterology criteria for pancreatic surveillance.Conclusions: Genetic testing of individuals with a FH of pancreatic cancer represents an opportunity to identify individuals who may be candidates for pancreatic surveillance.

Pancreatic Cancer Health Disparity: Pharmacologic Anthropology

“…Certain genetic mutations and inherited syndromes have been identified as risk factors for PCa. For example, mutations in genes such as BRCA1, BRCA2, PALB2, and ATM are associated with an increased risk of developing PCa [97][98][99]. These genetic factors can vary across populations, contributing to differences in PCa incidence and prevalence among different ethnic groups.…”

“…Variations in genes involved in drug metabolism and response pathways can contribute to disparities in treatment outcomes and side effects among different populations. The tumor microenvironment, including the immune system and stromal components, influences PCa progression and treatment response [88,90,98,106].…”