Prevalence of the N34S mutation of SPINK1 (serine protease inhibitor, Kazal type 1) in patients with chronic pancreatitis and pancreatic cancer

Introduction: In previous investigations, the N34S mutation of the serine protease inhibitor, Kazal type 1 (SPINK1) has been reported to have a connection with idiopathic and hereditary chronic pancreatitis, but the association between SPINK1 mutations and the incidence of chronic pancreatitis in alcoholics has been controversial. Additionally, it remains unknown whether the SPINK1 mutations have an impact on the clinical course of CP. No association between SPINK1 mutations and sporadic pancreatic cancer has been found. Aim: To determine the frequency of SPINK1 mutation in patients with alcoholic chronic pancreatitis (ACP), idiopathic chronic pancreatitis (ICP) and pancreatic cancer (PC). We also reviewed the clinical data of CP patients and analysed the differences of the clinical course of CP between patients with and without SPINK1 mutation. Material and methods: The diagnosis of CP was based on clinical examinations, ultrasound (US), computed tomography (CT) and endoscopic ultrasonography (EUS). DNA was isolated from 33 patients with ACP, 14 patients with ICP and 24 patients with PC. Forty-six healthy individuals were enrolled as controls. The N34S mutation of SPINK1 was detected with PCR-RFLP. Results: Among the CP group, in 6 patients (18%) with ACP and 4 patients (28.6%) with idiopathic CP, N34S mutation of SPINK1 was detected. The frequency of SPINK1 mutation was significantly higher (p < 0.024) than in controls (6.5%); OR was 5.733 (95% CI 1.218-26.959). No relations were detected between presence of this mutation and demographic data, as well as other clinical features of the CP patients. Among patients with a pancreatic cancer, the N34S mutation was present in 1 patient (4%). There was no difference in the frequency of the N34S mutation between patients with pancreatic cancer and controls (p = 0.687, OR 0.623, 95% CI 0.085-4.696). Conclusions: These preliminary data suggest the high incidence of N34S SPINK1 mutation in the Polish population generally, as well as in ICP. It may be speculated that this mutation contributes to the development of chronic pancreatitis in patients with alcohol overindulgence. Further studies are needed to explore the role of SPINK1 in the carcinogenesis of pancreatic cancer.