Familial pancreatic cancer and inherited risk (who qualifies for surveillance)

Definition and risk. A familial pancreatic cancer kindred has at least one pair of first-degree relatives with pancreatic cancer. In the Johns Hopkins National Familial Pancreas Tumor Registry (5,179 people from 838 kindreds), members of such kindreds with a first-degree relative affected had 9.0 times the expected incidence, rising to 6.4 times with two and 32 times with three affected first-degree relatives, while members of sporadic kindreds (1.8 times) and genetically unrelated spouses had no significant excess (Klein 2004); Cancer Research UK puts the risk from one first-degree relative at 62 to 76 percent higher. Genes explain a minority: 5.5 percent of 3,030 unselected patients carried a pathogenic variant in ATM, BRCA2, BRCA1, CDKN2A, TP53 or MLH1 (7.9 percent of those with a family history, 5.2 percent without) (Hu 2018), and most carriers have no family history (Shindo 2017); the syndromes with the highest relative risks are Peutz-Jeghers (more than 100 times), familial atypical multiple mole melanoma with CDKN2A (13 to 38 times) and hereditary pancreatitis with PRSS1 (more than 50 times) (Cancer Research UK). Who is offered surveillance. NICE NG85 offers it to hereditary pancreatitis with PRSS1, to BRCA1, BRCA2, PALB2 or CDKN2A carriers with one or more affected first-degree relatives, and to Peutz-Jeghers syndrome (1.1.15), and asks clinicians to consider it for two or more affected first-degree relatives across two generations and for Lynch syndrome with an affected first-degree relative (1.1.16), by MRI/MRCP or EUS (1.1.17). The International CAPS consortium (2020) starts familial surveillance at 50 or 55, or ten years before the youngest affected relative, uses EUS and MRI/MRCP yearly and added ATM carriers with one affected relative (Goggins 2020). What surveillance finds. In CAPS5, 77.8 percent of surveillance-detected cancers were stage I, and across CAPS1 to 5 five-year survival for screen-detected disease was 73.3 percent (Dbouk 2022); the Dutch programme found a 9.3 percent cumulative incidence in mutation carriers but none in mutation-negative familial kindreds over 63 months (Overbeek 2022); the Dutch CDKN2A cohort had a 20.7 percent cumulative incidence by age 70 with 83.3 percent of cancers resectable at imaging (Klatte 2022); the UK EUROPAC registry found one cancer and 41 cystic lesions in 321 people, the branch-duct IPMNs unrelated to inherited risk (Sheel 2019). The PRECEDE consortium is enrolling 20,000 people to standardise the approach (Gonda 2021; its trial record is linked). Practical route in the UK: ask the oncology team or GP for a clinical genetics referral; germline testing is offered to every patient with pancreatic cancer, and a positive result opens surveillance to relatives.