Natural history of SPINK1 germline mutation related-pancreatitis

Muller, Nelly, Sarantitis, Ioannis ORCID: 0000-0002-3905-1417, Rouanet, Marie, de Mestier, Louis, Halloran, CM ORCID: 0000-0002-5471-4178 and Greenhalf, William (2019) Natural history of SPINK1 germline mutation related-pancreatitis. EBioMedicine, 48. pp. 581-591.

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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.

Item Type:	Article
Uncontrolled Keywords:	SPINK1, Genetic, Pancreatitis, Diabetes, Pancreatic exocrine insufficiency, Pancreatic cancer
Depositing User:	Symplectic Admin
Date Deposited:	01 Oct 2019 07:20
Last Modified:	19 Jan 2023 00:25
DOI:	10.1016/j.ebiom.2019.09.032
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3056465