Germline mutations in pancreatic cancer susceptibility genes were commonly identified in a group of patients with pancreatic cancer who did not report a significant family history of cancer, according to the results of a single-center study.
Some of the gene mutations were therapeutically targetable, and would have been missed if patients were screened only on the basis of a family history of disease, according to Koji Shindo, of the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, and colleagues.
“Our results for pancreatic cancer highlight the limitations of relying solely on current NCCN family history guidelines to determine which patients are most likely to carry a deleterious pancreatic cancer susceptibility gene,” they wrote in a study published in the Journal of Clinical Oncology.
“The potential to benefit the few individuals with actionable gene mutations would seem to justify the effort to routinely offer gene testing to all patients with pancreatic ductal adenocarcinoma to identify such cases,” wrote Shindo and colleagues. “However, offering widespread genetic testing for patients with pancreatic cancer has significant challenges, not the least being that patients should undergo genetic counseling before and after such testing to provide understanding and reassurance and to avoid harm.”
The study population included 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic disease who underwent pancreatic resection at Johns Hopkins from 2000 to 2015. Using DNA prepared from normal tissue, the researchers sequenced 32 genes, including known pancreatic susceptibility genes.
Thirty-three patients—about 4% of patients with pancreatic adenocarcinoma—had deleterious germline mutations, 31 of which affected known familial pancreatic cancer susceptibility genes. Only three of these patients had reported a family history of pancreatic cancer, and most had no cancer family history to suggest an inherited cancer syndrome.
The most commonly identified mutations were BRCA2 in 12 patients and ATM in 10 patients. Additional mutations included BRCA1 (3 patients), MLH1 (2 patients), PALB2 (2 patients), TP53 (1 patient), and CDKN2A (1 patient). The researchers also found deleterious mutations in BUB3 (1 patient) and BUB1B (1 patient). Patients found to have these germline mutations were significantly younger than those without (60.8 years vs 65.1 years; P = .03).
Only five of 288 patients with a diagnosis of a periampullary neoplasm had an identifiable deleterious germline mutation.
“Because cancer genetics risk assessment is not a routine component of pancreatic cancer care, it would be valuable to undertake studies to determine the benefits and challenges of incorporating risk assessment and gene testing into routine pancreatic cancer practice,” the researchers wrote. “Additional studies are also needed to determine how cancer family history and other risk factor information can help refine pancreatic cancer risk in mutation carriers.”