title: Polymorphisms of SPINK1 N34S and CFTR in patients with sporadic and familial pancreatic cancer.
abstract: Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of developing pancreatic cancer through the development of chronic pancreatitis. DNA from patients with histologically-confirmed surgically-treated chronic pancreatitis, familial and sporadic pancreatic adenocarcinoma and controls were analyzed for the N34S polymorphism of SPINK1 and the two commonest polymorphisms of the CFTR gene, the DF508 mutation and the 5T polymorphism. These polymorphisms were determined using restriction fragment length polymorphism, PCR and cycle sequencing methods. The SPINK1 N34S polymorphism was detected in 5 of 172 (2.9%) patients with chronic pancreatitis, in 4 of 200 (2.0%) patients with sporadic pancreatic adenocarcinoma, in 0 of 36 (0%) of patients with familial pancreatic cancer and in 3 of 177 (1.7%) controls of chronic cholecystitis. The CFTR 5T polymorphism was identified in 31 of 334 (9.3%) patients of sporadic pancreatic cancer, in 5 of 43 (11.6%) patients with familial pancreatic cancer and in 10 of 112 (8.9%) controls with colorectal cancer. The CFTR DF508 mutation was recognized in 6 of the 240 (2.5%) patients with pancreatic adenocarcinoma, a prevalence similar to that of control populations. We conclude that the N34S polymorphism of SPINK1 and the 5T and DF508 CFTR polymorphisms do not predispose to the development of pancreatic adenocarcinoma. Furthermore, the N34S polymorphism is rarely found in patients with severe idiopathic chronic pancreatitis.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsubayashi
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Kieran
authors.initials: K
authors.lastname: Brune
authors.forename: Marcia
authors.initials: M
authors.lastname: Canto
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010195:Pancreatitis / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic