title: Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase (CEL) gene as risk factors in pancreatic cancer.
abstract: OBJECTIVE
  We have recently described copy number variants (CNVs) of the human carboxyl-ester lipase (CEL) gene, including a recombined deletion allele (CEL-HYB) that is a genetic risk factor for chronic pancreatitis. Associations with pancreatic disease have also been reported for the variable number of tandem repeat (VNTR) region located in CEL exon 11. Here, we examined if CEL CNVs and VNTR length polymorphisms affect the risk for developing pancreatic cancer.
  
  
  METHODS
  CEL CNVs and VNTR were genotyped in a German family with non-alcoholic chronic pancreatitis and pancreatic cancer, in 265 German and 197 Norwegian patients diagnosed with pancreatic adenocarcinoma, and in 882 controls. CNV screening was performed using PCR assays followed by agarose gel electrophoresis whereas VNTR lengths were determined by DNA fragment analysis.
  
  
  RESULTS
  The investigated family was CEL-HYB-positive. However, an association of CEL-HYB or a duplication CEL allele with pancreatic cancer was not seen in our two patient cohorts. The frequency of the 23-repeat VNTR allele was borderline significant in Norwegian cases compared to controls (1.2% vs. 0.3%; P = 0.05). For all other VNTR lengths, no statistically significant difference in frequency was observed. Moreover, no association with pancreatic cancer was detected when CEL VNTR lengths were pooled into groups of short, normal or long alleles.
  
  
  CONCLUSIONS
  We could not demonstrate an association between CEL CNVs and pancreatic cancer. An association is also unlikely for CEL VNTR lengths, although analyses in larger materials are necessary to completely exclude an effect of rare VNTR alleles.
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Monica
authors: M
authors: Dalva
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Khadija
authors: K
authors: El Jellas
authors: Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Solrun J
authors: SJ
authors: Steine
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Bente B
authors: BB
authors: Johansson
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Monika
authors: M
authors: Ringdal
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Janniche
authors: J
authors: Torsvik
authors: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Heike
authors: H
authors: Immervoll
authors: Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway.
authors: Dag
authors: D
authors: Hoem
authors: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors: Felix
authors: F
authors: Laemmerhirt
authors: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors: Peter
authors: P
authors: Simon
authors: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors: Markus M
authors: MM
authors: Lerch
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors: Stefan
authors: S
authors: Johansson
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors: Pål R
authors: PR
authors: Njølstad
authors: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors: Frank U
authors: FU
authors: Weiss
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. Electronic address: karianne.fjeld@uib.no.
authors: Karianne
authors: K
authors: Fjeld
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Anders
authors: A
authors: Molven
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats; D010190:Pancreatic Neoplasms / Q000235:genetics*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C054621:CEL protein, human; D008049:Lipase
keywords: Allele frequency; Carboxyl-ester lipase; Copy number variation; Genotyping; Pancreatic cancer; Variable number of tandem repeats