Background and aims: An increased risk of pancreatic adenocarcinoma (PA) in patients with hereditary pancreatitis (HP) was previously demonstrated in two multinational studies. The PA frequency in this setting is however unknown due to lack of exhaustive case collection. The aims of this study were to evaluate the standardized incidence ratio (SIR) of PA in an exhaustive national series of patients with HP and to search for risk factors.
Methods: All French genetic laboratories (response rate 100%), pediatricians, and gastroenterologists (response rate 84%) were contacted.
Inclusion criteria: mutation in the PRSS1 gene or recurrent, acute, or chronic pancreatitis, with no precipitating factors in two first-degree relatives or >or=3 second-degree relatives in >or=2 generations. Diagnosis of PA was based on histological records.
Results: Seventy-eight families and 200 patients were included (181 alive, 6,673 person-years, median number of generations 3, men 53%, alcoholism 5%, and smoking 34%). PRSS1 mutations were searched for in 96% of the patients and were detected in 68% (maternal inheritance 54%, R122H 78%, N29I 12%, and others 10%). Ten PA were diagnosed (median age 55 yr). SIR of PA for the whole population, men, and women were 87 (95% CI 42-113), 69 (25-150), and 142 (38-225), respectively, with no influence of genetic mutation. At ages 50 and 75 yr, the cumulated risk of PA was 11% and 49% for men and 8% and 55% for women, respectively. Smoking and diabetes mellitus were the main associated risk factors.
Conclusion: Patients with HP have a marked relative and absolute increased risk of PA as compared to the general population, especially in smokers. There is no correlation with the type of PRSS1 mutation.