Background/aim: Hereditary pancreatitis (HP) is the strongest known risk factor for pancreatic cancer. The aim of the present study is to establish diagnostic criteria for HP to predict and identify high-risk groups for pancreatic cancer.
Method: We collected clinical data for 210 patients with recurrent acute or chronic pancreatitis, and examined mutations of the cationic trypsinogen (CT) gene in 57 patients with a family history of pancreatitis or with early-onset idiopathic recurrent acute or chronic pancreatitis (40 years of age or younger). DNA was extracted from peripheral blood leukocytes, and exons 2 and 3 of the CT gene were individually amplified by polymerase chain reaction (PCR) and sequenced.
Results: Of these 57 patients in whom mutations of the CT gene were examined, the R122H (20 patients) and N29I (5 patients) mutations in the CT gene were observed in 25 patients (43.9%). From the analysis of clinical records and the CT gene of these patients, we proposed the following adaptations to the diagnostic criteria for HP: (1) at least one of the affected members in a family has no known etiological factors, (2) we deleted the definition of "different generation", but included the upper limit of the age of onset of pancreatitis in the case of siblings (at least 1 of the patients in a family <40 years of age). According to these criteria, all patients with the CT gene mutations in the present study could be classified as having HP, with the exception of 2 sporadic cases with the R122H and N29I mutations, respectively. Based on these findings, we revised the criteria for the diagnosis of HP; (1) recurrent acute or chronic pancreatitis with R122H or N29I mutation of the CT gene, or (2) recurrent acute or chronic pancreatitis with a family history of 2 or more affected patients, irrespective of generation, with at least 1 of the patients having no known etiological factors, and in case of siblings only, the onset of the disease in at least 1 of the patients is under age 40 years.
Conclusion: The revised criteria in the present study are appropriate and of clinical usefulness to diagnose patients with HP even in cases without the genetic testing. However, if and when more genes are detected, it will be important to reexamine the mutation-negative patients now classified as HP based on our proposed criteria.