Monica Dalva1, Khadija El Jellas2, Solrun J Steine3, Bente B Johansson4, Monika Ringdal4, Janniche Torsvik5, Heike Immervoll6, Dag Hoem7, Felix Laemmerhirt8, Peter Simon8, Markus M Lerch8, Stefan Johansson4, Pål R Njølstad9, Frank U Weiss8, Karianne Fjeld10, Anders Molven2. 1. 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. 2. 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. 3. Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway. 4. 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. 5. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. 6. Department of Pathology, Haukeland University Hospital, Bergen, Norway. 7. Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway. 8. Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. 9. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway. 10. 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.
Abstract
BACKGROUND/ OBJECTIVES: 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.
BACKGROUND/ OBJECTIVES: We have recently described copy number variants (CNVs) of the humancarboxyl-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: Khadija El Jellas; Bente B Johansson; Karianne Fjeld; Aristotelis Antonopoulos; Heike Immervoll; Man H Choi; Dag Hoem; Mark E Lowe; Dominique Lombardo; Pål R Njølstad; Anne Dell; Eric Mas; Stuart M Haslam; Anders Molven Journal: J Biol Chem Date: 2018-10-12 Impact factor: 5.157
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Authors: Irina Mihaela Cazacu; Nelli Farkas; András Garami; Márta Balaskó; Bernadett Mosdósi; Hussain Alizadeh; Zoltán Gyöngyi; Zoltán Rakonczay; Éva Vigh; Tamás Habon; László Czopf; Marilena Alina Lazarescu; Bálint Erőss; Miklós Sahin-Tóth; Péter Hegyi Journal: Pancreas Date: 2018-10 Impact factor: 3.327
Authors: Monica Dalva; Ida K Lavik; Khadija El Jellas; Anny Gravdal; Aurelia Lugea; Stephen J Pandol; Pål R Njølstad; Richard T Waldron; Karianne Fjeld; Bente B Johansson; Anders Molven Journal: Cells Date: 2020-01-18 Impact factor: 6.600
Authors: Anny Gravdal; Xunjun Xiao; Miriam Cnop; Khadija El Jellas; Stefan Johansson; Pål R Njølstad; Mark E Lowe; Bente B Johansson; Anders Molven; Karianne Fjeld Journal: J Biol Chem Date: 2021-04-14 Impact factor: 5.157