Genetic predisposition to pancreatic cancer

Table 3 Proposed inclusion criteria for pancreatic adenocarcinoma screening programs in high-risk individuals, identified based on family history and possibly on genetic background

Current (based on family history alone or on genetic background):

Family history:

Three or more relatives in the same lineage affected by PC

Two relatives affected by PC, at least one of which is a FDR of the individual

Hereditary pancreatitis

> 10-fold increased risk as established by PancPRO

Genetic background:

Germline carrier of a mutation in a candidate gene with at least one FDR or SDR affected by PC

Mutation-positive individual in a PJS kindred

Proposed (based on family history and genetic background):

Family history: Identification of a hereditary syndrome or a 10-fold increased risk established by PancPRO

Genetic background: According to testing in candidate genes (CDKN2A, BRCA1-2, ATM, PALB2, STK11, PRSS1, SPINK1…)

Mutation identified: Propose screening to carriers of germline mutation

No mutation identified: Propose screening to all HRIs

In populations with a high prevalence of germline mutations in candidate genes (e.g., CDKN2A founder mutations in Italy or the Netherlands)

The same as above + test candidate genes according to specific genetic background, even in the absence of all criteria for hereditary syndromes or of a PancPRO score > 10

PC: Pancreatic adenocarcinoma; FDR: First-degree relative; PJS: Peutz-Jeghers syndrome; HRIs: High-risk individuals.