title: A Common CCK-B Receptor Intronic Variant in Pancreatic Adenocarcinoma in a Hungarian Cohort.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Anita
authors.initials: A
authors.lastname: Balázs
authors.forename: Balázs Csaba
authors.initials: BC
authors.lastname: Németh
authors.forename: Balázs
authors.initials: B
authors.lastname: Ördög
authors.forename: Eszter
authors.initials: E
authors.lastname: Hegyi
authors.forename: István
authors.initials: I
authors.lastname: Hritz
authors.forename: László
authors.initials: L
authors.lastname: Czakó
authors.forename: József
authors.initials: J
authors.lastname: Czimmer
authors.forename: Szilárd
authors.initials: S
authors.lastname: Gódi
authors.forename: Adrienn
authors.initials: A
authors.lastname: Csiszkó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Andrea
authors.initials: A
authors.lastname: Párniczky
authors.forename: Ferenc
authors.initials: F
authors.lastname: Izbéki
authors.forename: Adrienn
authors.initials: A
authors.lastname: Halász
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kahán
authors.forename: Péter
authors.initials: P
authors.lastname: Hegyi
authors.forename: Miklós
authors.initials: M
authors.lastname: Sahin-Tóth
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D006814:Hungary; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D011379:Prognosis; D012326:RNA Splicing / Q000235:genetics; D043887:Receptor, Cholecystokinin B / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D043887:Receptor, Cholecystokinin B