Bruna Dalmasso, Eleonora Allavena, Andrea Gambino, Francesca Barbero, Irene Vanni, Cansu Gorgun, Giuseppe Cittadini, Francesco Spagnolo, Enrica Teresa Tanda, Andrea Boutros, William Bruno, Lorenza Pastorino, Paola Ghiorzo
In this Italian cohort, SIR approached Dutch estimates, with similar cumulative incidence, but at older ages. Incorporating region-specific risk and age of onset may help tailor PC screening in high-risk individuals, improving efficacy, adherence and sustainability. Our data support the inclusion of all CDKN2A PV carriers in surveillance programs, starting not earlier than age 40.
BACKGROUND: Pancreatic cancer (PC) risk in carriers of germline CDKN2A pathogenic variants (PV) is among the highest, with a standardized incidence ratio (SIR) of 20 and cumulative incidence >20% by age 70 in Dutch cohorts, informing surveillance protocols with promising results in CDKN2A-positive families. Prospective, lifetime, variant-specific estimates are missing in Italy.
PATIENTS AND METHODS: We assessed SIR and cumulative incidence of PC in 202 kindreds carrying germline CDKN2A PV, mostly melanoma-selected and followed for up to 25 years.
RESULTS: PC occurred in about one-third of families, with median age at diagnosis of 66 years. Compared with regional cancer registry PC incidence rates, SIR was 34.26 [95%CI= 27.12-42.7]. Cumulative incidence was <1% until age 52, 10% by 70, and 19% after 90. Variant-specific estimates were higher for E27X than G101W (SIR 38.68 and 31.17; cumulative incidence 22% and 18%, respectively).
CONCLUSION: In this Italian cohort, SIR approached Dutch estimates, with similar cumulative incidence, but at older ages. Incorporating region-specific risk and age of onset may help tailor PC screening in high-risk individuals, improving efficacy, adherence and sustainability. Our data support the inclusion of all CDKN2A PV carriers in surveillance programs, starting not earlier than age 40.