Anita Balázs1, Balázs Csaba Németh, Balázs Ördög, Eszter Hegyi, István Hritz, László Czakó, József Czimmer, Szilárd Gódi, Adrienn Csiszkó, Zoltán Rakonczay, Andrea Párniczky, Ferenc Izbéki, Adrienn Halász, Zsuzsanna Kahán, Péter Hegyi, Miklós Sahin-Tóth. 1. From the *First Department of Medicine, University of Szeged, Szeged, Hungary; †Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA; ‡Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary; §2nd Department of Pediatrics, Comenius University Medical School, University Children's Hospital, Bratislava, Slovakia; ∥First Department of Internal Medicine, University of Pécs, Hungary; ¶Institute of Surgery, University of Debrecen, Clinical Center, Debrecen, Hungary; #Heim Pál Children's Hospital, Budapest, Hungary; **First Department of Medicine, Szent György Teaching Hospital of County Fejér, Székesfehérvár, Hungary; ††Department of Oncotherapy, University of Szeged, Szeged, Hungary; and ‡‡MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary.
Abstract
OBJECTIVES: Variant c.811+32C>A in intron 4 of the cholecystokinin-B receptor gene (CCKBR) was reported to correlate with higher pancreatic cancer risk and poorer survival. The variant was suggested to induce retention of intron 4, resulting in a new splice form with enhanced receptor activity. Our objective was to validate the c.811+32C>A variant as an emerging biomarker for pancreatic cancer risk and prognosis. METHODS: We genotyped variant c.811+32C>A in 122 pancreatic adenocarcinoma case patients and 106 control subjects by sequencing and examined its association with cancer risk and patient survival. We tested the functional effect of variant c.811+32C>A on pre-messenger RNA splicing in human embryonic kidney 293T and Capan-1 cells transfected with CCKBR minigenes. RESULTS: The allele frequency of the variant was similar between patients and control subjects (18.4% and 17.9%, respectively). Survival analysis showed no significant difference between median survival of patients with the C/C genotype (266 days) and patients with the A/C or A/A genotypes (257 days). CCKBR minigenes with or without variant c.811+32C>A exhibited no difference in expression of the intron-retaining splice variant. CONCLUSION: These data indicate that variant c.811+32C>A in CCKBR does not have a significant impact on pancreatic cancer risk or survival in a Hungarian cohort.
OBJECTIVES: Variant c.811+32C>A in intron 4 of the cholecystokinin-B receptor gene (CCKBR) was reported to correlate with higher pancreatic cancer risk and poorer survival. The variant was suggested to induce retention of intron 4, resulting in a new splice form with enhanced receptor activity. Our objective was to validate the c.811+32C>A variant as an emerging biomarker for pancreatic cancer risk and prognosis. METHODS: We genotyped variant c.811+32C>A in 122 pancreatic adenocarcinoma case patients and 106 control subjects by sequencing and examined its association with cancer risk and patient survival. We tested the functional effect of variant c.811+32C>A on pre-messenger RNA splicing in humanembryonic kidney293T and Capan-1 cells transfected with CCKBR minigenes. RESULTS: The allele frequency of the variant was similar between patients and control subjects (18.4% and 17.9%, respectively). Survival analysis showed no significant difference between median survival of patients with the C/C genotype (266 days) and patients with the A/C or A/A genotypes (257 days). CCKBR minigenes with or without variant c.811+32C>A exhibited no difference in expression of the intron-retaining splice variant. CONCLUSION: These data indicate that variant c.811+32C>A in CCKBR does not have a significant impact on pancreatic cancer risk or survival in a Hungarian cohort.
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Authors: Laufey Amundadottir; Peter Kraft; Rachael Z Stolzenberg-Solomon; Charles S Fuchs; Gloria M Petersen; Alan A Arslan; H Bas Bueno-de-Mesquita; Myron Gross; Kathy Helzlsouer; Eric J Jacobs; Andrea LaCroix; Wei Zheng; Demetrius Albanes; William Bamlet; Christine D Berg; Franco Berrino; Sheila Bingham; Julie E Buring; Paige M Bracci; Federico Canzian; Françoise Clavel-Chapelon; Sandra Clipp; Michelle Cotterchio; Mariza de Andrade; Eric J Duell; John W Fox; Steven Gallinger; J Michael Gaziano; Edward L Giovannucci; Michael Goggins; Carlos A González; Göran Hallmans; Susan E Hankinson; Manal Hassan; Elizabeth A Holly; David J Hunter; Amy Hutchinson; Rebecca Jackson; Kevin B Jacobs; Mazda Jenab; Rudolf Kaaks; Alison P Klein; Charles Kooperberg; Robert C Kurtz; Donghui Li; Shannon M Lynch; Margaret Mandelson; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Sara H Olson; Kim Overvad; Alpa V Patel; Petra H M Peeters; Aleksandar Rajkovic; Elio Riboli; Harvey A Risch; Xiao-Ou Shu; Gilles Thomas; Geoffrey S Tobias; Dimitrios Trichopoulos; Stephen K Van Den Eeden; Jarmo Virtamo; Jean Wactawski-Wende; Brian M Wolpin; Herbert Yu; Kai Yu; Anne Zeleniuch-Jacquotte; Stephen J Chanock; Patricia Hartge; Robert N Hoover Journal: Nat Genet Date: 2009-08-02 Impact factor: 38.330
Authors: Gloria M Petersen; Laufey Amundadottir; Charles S Fuchs; Peter Kraft; Rachael Z Stolzenberg-Solomon; Kevin B Jacobs; Alan A Arslan; H Bas Bueno-de-Mesquita; Steven Gallinger; Myron Gross; Kathy Helzlsouer; Elizabeth A Holly; Eric J Jacobs; Alison P Klein; Andrea LaCroix; Donghui Li; Margaret T Mandelson; Sara H Olson; Harvey A Risch; Wei Zheng; Demetrius Albanes; William R Bamlet; Christine D Berg; Marie-Christine Boutron-Ruault; Julie E Buring; Paige M Bracci; Federico Canzian; Sandra Clipp; Michelle Cotterchio; Mariza de Andrade; Eric J Duell; J Michael Gaziano; Edward L Giovannucci; Michael Goggins; Göran Hallmans; Susan E Hankinson; Manal Hassan; Barbara Howard; David J Hunter; Amy Hutchinson; Mazda Jenab; Rudolf Kaaks; Charles Kooperberg; Vittorio Krogh; Robert C Kurtz; Shannon M Lynch; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Hemang Parikh; Alpa V Patel; Petra H M Peeters; Aleksandar Rajkovic; Elio Riboli; Laudina Rodriguez; Daniela Seminara; Xiao-Ou Shu; Gilles Thomas; Anne Tjønneland; Geoffrey S Tobias; Dimitrios Trichopoulos; Stephen K Van Den Eeden; Jarmo Virtamo; Jean Wactawski-Wende; Zhaoming Wang; Brian M Wolpin; Herbert Yu; Kai Yu; Anne Zeleniuch-Jacquotte; Joseph F Fraumeni; Robert N Hoover; Patricia Hartge; Stephen J Chanock Journal: Nat Genet Date: 2010-01-24 Impact factor: 38.330