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. 2019 Oct:48:581-591.
doi: 10.1016/j.ebiom.2019.09.032. Epub 2019 Oct 15.

Natural history of SPINK1 germline mutation related-pancreatitis

Nelly Muller  1 , Ioannis Sarantitis  2 , Marie Rouanet  3 , Louis de Mestier  1 , Christopher Halloran  2 , William Greenhalf  2 , Claude Férec  4 , Emmanuelle Masson  4 , Philippe Ruszniewski  1 , Philippe Lévy  1 , John Neoptolemos  5 , Louis Buscail  3 , Vinciane Rebours  6
Affiliations

Natural history of SPINK1 germline mutation related-pancreatitis

Nelly Muller et al. EBioMedicine. 2019 Oct.

Abstract

Background: The aim was to describe genetic, clinical and morphological features in a large, multicentre European cohort of patients with SPINK1 related pancreatitis, in comparison with patients with idiopathic pancreatitis (IP).

Methods: All SPINK1 mutation carriers with pancreatic symptoms from two French and one English centers were included. Patients with IP were included in a control group. Genetic, clinical, radiological and biochemical data were collected.

Findings: 209 and 302 patients were included in the SPINK1 and control groups (median follow-up: 8.3 years (3.7-17.4) vs 5.3 (2.5-8.8)). The median age at onset of symptoms was 20.1 years (17.5-22.8) in the SPINK1 group versus 41.2 (35.2-45.2). The age of exocrine pancreatic insufficiency (EPI) onset in the SPINK1 group was 49.5 (44.5-54.6) years vs. 65.2 (62.1-68.3), p < 0.001. SPINK1 patients with EPI were 5.3%, 14.7%, 28.3% and 52.4% at 20, 30, 40 and 50 years. Diabetes occurred 37.7 (33.3-42.1) years following the onset of symptoms in the SPINK1 group vs. 30.6 (17.3-43.8) (p = 0.002). SPINK1 patients with diabetes were 7.8%, 13.4%, 26.3% and 43.4% at 30, 40, 50 and 60 years. Seven patients (3.3%) developed pancreatic cancer in the SPINK1 group (versus 3 (0.99%), p = 0.1), at a median age of 60 vs 66 years. The cancer risk was 0.8% before 50 years, 11.9%, 27.7%, 51.8% at 60, 70 and 80 years and was 12 times higher than in controls (Cox HR 12.0 (3.0-47.8), p < 0.001).

Interpretation: SPINK1 related pancreatitis is associated with earlier onset and pancreatic insufficiencies. p.N34S SPINK1 may well be associated with cancer.

Keywords: Diabetes; Genetic; Pancreatic cancer; Pancreatic exocrine insufficiency; Pancreatitis; SPINK1.

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Conflict of interest statement

No conflicts of interest exist.

Figures

Fig. 1
Fig. 1
Cumulative incidence of symptoms depending on age.
Fig. 2
Fig. 2
Cumulative incidence of chronic pancreatitis depending on age (2a) and according to tobacco status (2b).
Fig. 3
Fig. 3
Cumulative incidence of steatorrhea depending on age (3a) and depending on tobacco status (3b).
Fig. 4
Fig. 4
Cumulative incidence of mellitus diabetes depending on age (4a) and depending on tobacco status (4b).
Fig. 5
Fig. 5
Cumulative incidence of pancreatic ductal adenocarcinoma cancer depending on age.
See this image and copyright information in PMC

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