title: Hereditary pancreatitis as the premalignant disease: a Japanese case of pancreatic cancer involving the SPINK1 gene mutation N34S.
abstract: Mutations in the cationic trypsinogen gene are acknowledged as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. However, whether patients with mutations in other genes, such as the serine protease inhibitor Kazal type 1 (SPINK1) gene, are also at a higher risk of pancreatic cancer remains unknown. We report a case of pancreatic cancer associated with chronic calcifying pancreatitis in a patient with a homozygous N34S mutation in the SPINK1 gene. A 44-year-old woman was hospitalized due to obstructive jaundice. Preoperative examination showed a tumor in the head of the pancreas and multiple pancreatic stones; pancreatoduodenectomy revealed a solid tumor, 3.0 x 2.5 cm in size, in the head of the pancreas, and numerous pancreatic stones throughout the pancreas. Pathologic studies revealed moderately differentiated tubular adenocarcinoma. Mutational analyses of the SPINK1 and PRSS1 genes in members of the patient's family were carried out. The homozygous N34S mutation in the SPINK1 gene was found in the patient and her older sister, who was previously diagnosed with chronic calcific pancreatitis and had undergone the Frey operation. The patient's parents and brother were unaffected carriers of the N34S heterozygous mutation. No family members had any mutations in the cationic trypsinogen gene. To our knowledge, this is the first reported case of chronic pancreatitis accompanied by pancreatic cancer in a patient with the SPINK1 N34S mutation. Although this case does not meet the classic criteria of hereditary pancreatitis, it does suggest that the SPINK1 N34S mutation may be associated with cancer development in patients with hereditary pancreatitis. Further prospective, multicenter trials investigating secondary screening for pancreatic cancer in hereditary pancreatitis are necessary to clarify the role of SPINK1 mutations in the development of pancreatic cancer.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Hiroya
authors.initials: H
authors.lastname: Mizutamari
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kume
authors.forename: Tooru
authors.initials: T
authors.lastname: Asakura
authors.forename: Kennichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000328:Adult; D019943:Amino Acid Substitution; D002760:Cholangiopancreatography, Endoscopic Retrograde; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D010195:Pancreatitis / Q000150:complications* / Q000235:genetics; D010375:Pedigree; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*
chemical_list: D014359:Trypsin Inhibitor, Kazal Pancreatic