Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase ( CEL ) gene as risk factors in pancreatic cancer

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 17; no. 1; pp. 83 - 88
• Main Authors: Dalva, Monica, El Jellas, Khadija, Steine, Solrun J, Johansson, Bente B, Ringdal, Monika, Torsvik, Janniche, Immervoll, Heike, Hoem, Dag, Laemmerhirt, Felix, Simon, Peter, Lerch, Markus M, Johansson, Stefan, Njølstad, Pål R, Weiss, Frank U, Fjeld, Karianne, Molven, Anders
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01-01-2017; Elsevier Limited
• Subjects: Adenocarcinoma - genetics; Allele frequency; Biomarkers, Tumor - genetics; Carboxyl-ester lipase; Case-Control Studies; Copy number variation; Deoxyribonucleic acid; Diabetes; DNA; DNA Copy Number Variations; Endocrinology & Metabolism; Female; Gastroenterology and Hepatology; Genes; Genotyping; Health risk assessment; Humans; Lipase - genetics; Male; Minisatellite Repeats; Mutation; Pancreatic cancer; Pancreatic Neoplasms - genetics; Risk Factors; Variable number of tandem repeats; Allele frequency; Copy number variation; Variable number of tandem repeats; Genotyping; Carboxyl-ester lipase; Pancreatic cancer
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1016/j.pan.2016.10.006

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.