A Common CCK-B Receptor Intronic Variant in Pancreatic Adenocarcinoma in a Hungarian Cohort

on behalf of the Hungarian Pancreatic Study Group

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalPancreas.
DOIs
Publication statusAccepted/In press - Dec 5 2015

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Cholecystokinin B Receptor
Adenocarcinoma
Pancreatic Neoplasms
Introns
Survival
Genes
Genotype
RNA Splicing
Survival Analysis
Gene Frequency
Biomarkers
Kidney
Neoplasms

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

A Common CCK-B Receptor Intronic Variant in Pancreatic Adenocarcinoma in a Hungarian Cohort. / on behalf of the Hungarian Pancreatic Study Group.

In: Pancreas., 05.12.2015.

Research output: Contribution to journalArticle

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title = "A Common CCK-B Receptor Intronic Variant in Pancreatic Adenocarcinoma in a Hungarian Cohort",
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.",
author = "{on behalf of the Hungarian Pancreatic Study Group} and Anita Bal{\'a}zs and N{\'e}meth, {Bal{\'a}zs Csaba} and Bal{\'a}zs {\"O}rd{\"o}g and Eszter Hegyi and I. Hritz and L. Czak{\'o} and J{\'o}zsef Czimmer and Szil{\'a}rd G{\'o}di and Adrienn Csiszk{\'o} and Z. Rakonczay and Andrea P{\'a}rniczky and F. Izb{\'e}ki and Adrienn Hal{\'a}sz and Z. Kah{\'a}n and P. Hegyi and Mikl{\'o}s Sahin-T{\'o}th",
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T1 - A Common CCK-B Receptor Intronic Variant in Pancreatic Adenocarcinoma in a Hungarian Cohort

AU - on behalf of the Hungarian Pancreatic Study Group

AU - Balázs, Anita

AU - Németh, Balázs Csaba

AU - Ördög, Balázs

AU - Hegyi, Eszter

AU - Hritz, I.

AU - Czakó, L.

AU - Czimmer, József

AU - Gódi, Szilárd

AU - Csiszkó, Adrienn

AU - Rakonczay, Z.

AU - Párniczky, Andrea

AU - Izbéki, F.

AU - Halász, Adrienn

AU - Kahán, Z.

AU - Hegyi, P.

AU - Sahin-Tóth, Miklós

PY - 2015/12/5

Y1 - 2015/12/5

N2 - 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.

AB - 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.

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