Natural history of SPINK1 germline mutation related-pancreatitis

• Verfasst von: Muller, Nelly [VerfasserIn]
• Verfasst von: Sarantitis, Ioannis [VerfasserIn]
• Verfasst von: Rouanet, Marie [VerfasserIn]
• Verfasst von: de Mestier, Louis [VerfasserIn]
• Verfasst von: Halloran, Christopher [VerfasserIn]
• Verfasst von: Greenhalf, William [VerfasserIn]
• Verfasst von: Férec, Claude [VerfasserIn]
• Verfasst von: Masson, Emmanuelle [VerfasserIn]
• Verfasst von: Ruszniewski, Philippe [VerfasserIn]
• Verfasst von: Lévy, Philippe [VerfasserIn]
• Verfasst von: Neoptolemos, John P. [VerfasserIn]
• Verfasst von: Buscail, Louis [VerfasserIn]
• Verfasst von: Rebours, Vinciane [VerfasserIn]
• Titel: Natural history of SPINK1 germline mutation related-pancreatitis
• Verf.angabe: Nelly Muller, Ioannis Sarantitis, Marie Rouanet, Louis de Mestier, Christopher Halloran, William Greenhalf, Claude Férec, Emmanuelle Masson, Philippe Ruszniewski, Philippe Lévy, John Neoptolemos, Louis Buscail, Vinciane Rebours
• E-Jahr: 2019
• Jahr: 15 October 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 09.12.2019
• Titel Quelle: Enthalten in: EBioMedicine
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 2014
• Jahr Quelle: 2019
• Band/Heft Quelle: 48(2019), Seite 581-591
• ISSN Quelle: 2352-3964
• DOI: doi:10.1016/j.ebiom.2019.09.032
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Diabetes
• Sach-SW: Genetic
• Sach-SW: Pancreatic cancer
• Sach-SW: Pancreatic exocrine insufficiency
• Sach-SW: Pancreatitis
• Sach-SW: SPINK1
• K10plus-PPN: 1684857341

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.