Germline mutations in pancreatic cancer become better defined

open access

 KEY POINTS
Germline mutations occur in approximately 15% of patients with PAC.  These 2 studies suggest that genetic counseling and testing are appropriate for patients with early-onset PAC or a family history of PAC, those with one of several associated cancers, and those of Ashkenazi Jewish ancestry. Further study and guidelines are needed to integrate genetic testing for PAC into practice.

 A total of 159 patients pursued the
recommended genetic testing, and a
germline cancer susceptibility mutation
was found in 24 patients (15%).
Mutations were detected in BRCA2
in 13 patients, BRCA1 in 4 patients,
p16 in 2 patients, PALB2 in 1 patient,
and the DNA mismatch repair genes
related to Lynch syndrome in 4
patients. The mean age of the
patients with a pathologic mutation
was 58.5 years compared with 64
years for those without mutations.

The researchers at MSKCC say they believe the results of this study suggest that it is reasonable for patients who are diagnosed with PAC at a young age or who are of Ashkenazi Jewish ancestry to be referred for genetic counseling and testing.

“Additionally, it is important [to] advocate for coverage benefits of genetic counseling for patients with pancreatic cancer since many third-party payers primarily only focus on benefits for patients with breast, ovarian, and colorectal cancer,” says Dr. Stadler.

Two recent studies have helped to clarify the prevalence of germline mutations in patients with pancreatic adenocarcinoma (PAC). PAC has been linked to certain
inherited cancer susceptibility genes and such syndromes as hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2), familial atypical mole syndrome (p16), Lynch syndrome (MLH1, mutS homolog [MSH]2, MSH6, PMS2, and EPCAM),
Peutz-Jeghers syndrome (STK11), and partner and localizer of BRCA2 (PALB2)-associated PAC. However, the prevalence of germline mutations in patients with pancreatic cancer is not well defined. Data that better define the prevalence of particular germline mutations are needed to make evidence-based recommendations and better select patients with pancreatic cancer for genetic testing......