Assessment
➤ PCO 2.1 All patients diagnosed with pancreatic adenocarcinoma should undergo
assessment of risk for hereditary syndromes known to be associated with an
increased risk for pancreatic adenocarcinoma (Table 1). (Strong Statement;
IC-B)
• Assessment of risk includes obtaining a personal cancer history and family history of
cancers in 1st and 2nd degree relatives. However, recent data demonstrate that many
individuals who develop pancreatic cancer in the setting of genetic predisposition lack
clinical features or family cancer history typically associated with the corresponding
hereditary syndrome. Therefore, germline genetic testing may be discussed with patients
with personal history of pancreatic cancer, even if family history is unremarkable.
➤ PCO 2.2 An individual with a cancer diagnosis is often the best candidate in
whom to initiate genetic testing and has the highest likelihood of an informative
test result. (Strong Statement; IC-B)
• However, if a cancer-affected individual is not available, testing may be performed in
a pancreatic cancer-unaffected individual following genetic risk assessment with the
understanding that a negative test result is considered clinically uninformative.
• The following cancer-unaffected individuals should be offered genetic risk evaluation:
▶ Members of families with an identified pathogenic cancer susceptibility gene variant
▶ Pancreatic cancer-unaffected individuals from families that meet criteria for genetic
evaluation for known hereditary syndromes that are linked to pancreatic cancer
▶ Pancreatic cancer-unaffected individuals from families that meet criteria for familial
pancreatic cancer, as outlined in PCO 1.2
➤ PCO 2.3 Genetic testing in a patient with pancreatic cancer may confirm the
diagnosis of a hereditary cancer syndrome and inform management of at-risk
family members. (Moderate Statement; IC-B/H)
• Given the possibility that certain germline variants could potentially be used to guide
therapeutic decision-making and the limited prognosis of many pancreatic cancer
patients, the Expert Panel recommends that consideration of germline testing for
inherited cancer susceptibility should be performed early in the disease course for
patients with pancreatic cancer.
➤ PCO 2.4 Several genes have been linked to risk for pancreatic cancer (Table 1).
Unless a genetic diagnosis has previously been confirmed in a family member,
germline genetic testing should be performed using a multigene panel that
includes the genes listed in Table 1. (Strong Statement; IC-B)
• A finding of a pathogenic or likely pathogenic germline variant can confer increased risks
of cancers beyond the pancreas for the proband and their families.
• Finding a germline variant of uncertain significance is not considered to be causative of
increased cancer susceptibility.
