Germline mutations in pancreatic cancer susceptibility genes are often identified in patients with pancreatic cancer without a known family history of cancer, according to a recent study.
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Deleterious germline mutations factor in to pancreatic cancer susceptibility and are well documented in families with multiple members exhibiting pancreatic cancer. There is significant potential clinical utility to identifying germline susceptibility genes in patients with pancreatic cancer; mutation carriers have more options for personalized medicine directed toward the genetic drivers of their cancer, and their family members may benefit from pancreatic cancer screening and prevention strategies.
Koji Shindo, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, and colleagues conducted a study to gain further understanding of the prevalence of germline mutations in patients with apparently sporadic pancreatic cancer. Researchers sequenced 32 genes—including known pancreatic susceptibility genes—in DNA from normal tissue of 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic diseases who underwent pancreatic resection. The study was published in the Journal of Clinical Oncology (online August 2, 2017; doi:10.1200/JCO.2017.72.3502).
Researchers acknowledged that 33 patients (4% of those with pancreatic adenocarcinoma) had deleterious germline mutations, 31 (3.5%) of which affected known familial pancreatic cancer susceptibility genes. Among these patients, only three had documented family history of pancreatic cancer, and most had no cancer family history to indicate an inherited cancer syndrome.
The most commonly identified mutations were BRCA2 in 12 patients and ATM in 10 patients. Researchers also identified BRCA1 (n = 3 patients), MLH1 (n = 2 patients), PALB2 (n = 2 patients), TP53 (n = 1 patient), and CDKN2A (n = 1 patient).
Five (1.7%) of the patients with other periampullary neoplasms had a deleterious germline mutation.
Authors of the study concluded that germline mutations in pancreatic cancer susceptibility genes can be easily identified in patients with pancreatic cancer without a significant family history of cancer. The deleterious pancreatic cancer susceptibility gene mutations found in the study will be missed if current National Comprehensive Cancer Network family history guidelines are the main criteria used to determine the appropriateness of gene testing, they 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,” they added.—Zachary Bessette
