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

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• 作者：Monica Dalva^a ; ^b ; ^c ; Khadija El Jellas^a ; ^c ; ^d ; Solrun J. Steine^c ; Bente B. Johansson^a ; ^b ; Monika Ringdal^a ; ^b ; Janniche Torsvik^a ; Heike Immervoll^d ; Dag Hoem^e ; Felix Laemmerhirt^f ; Peter Simon^f ; Markus M. Lerch^f ; Stefan Johansson^a ; ^b ; På ; l R. Njø ; lstad^a ; ^g ; Frank U. Weiss^f ; Karianne Fjeld^a ; ^b ; ¹ ; ^{karianne.fjeld@uib.no} ; Anders Molven^a ; ^c ; ^d ; ¹
• 关键词：Allele frequency ; Carboxyl-ester lipase ; Copy number variation ; Genotyping ; Pancreatic cancer ; Variable number of tandem repeats
• 刊名：Pancreatology
• 出版年：2017
• 出版时间：January-February 2017
• 年：2017
• 卷：17
• 期：1
• 页码：83-88
• 全文大小：324 K
• 卷排序：17

文摘

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.MethodsCEL 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.ResultsThe 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.ConclusionsWe 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.