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Alsubai J, Matters GL, McGovern CO, et al. Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer. Clin Transl Gastroenterol. 2016;7:e134doi: 10.1038/ctg.2015.61.
Alsubai, J., Matters, G. L., McGovern, C. O., Liao, J., Gilius, E. L., & Smith, J. P. (2016). Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer. Clinical and translational gastroenterology, 7e134. https://doi.org/10.1038/ctg.2015.61
Alsubai, Jelal, et al. "Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer." Clinical and translational gastroenterology vol. 7 (2016): e134. doi: https://doi.org/10.1038/ctg.2015.61
Alsubai J, Matters GL, McGovern CO, Liao J, Gilius EL, Smith JP. Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer. Clin Transl Gastroenterol. 2016 Jan 07;7:e134. doi: 10.1038/ctg.2015.61. PMID: 26741064; PMCID: PMC4737870.
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Clin Transl Gastroenterol. 2016 Jan 07;7:e134. doi: 10.1038/ctg.2015.61.

Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer.

Clinical and translational gastroenterology

Jelal Alsubai, Gail L Matters, Christopher O McGovern, Jiangang Liao, Evan L Gilius, Jill P Smith

Affiliations

  1. Department of Medicine, Pennsylvania State University School of Medicine, Hershey, Pennsylvania, USA.
  2. Department of Biochemistry and Molecular Biology, Pennsylvania State University School of Medicine, Hershey, Pennsylvania, USA.
  3. Department of Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, USA.
  4. The National Cancer Institute, NIH, Bethesda, Maryland, USA.
  5. Department of Medicine/Gastroenterology Georgetown University School of Medicine, Washington, District of Columbia, USA.

PMID: 26741064 PMCID: PMC4737870 DOI: 10.1038/ctg.2015.61

Abstract

OBJECTIVES: Today, genetic biomarkers have been demonstrated to play an important role in identifying at-risk subjects for familial or inherited cancers. We have identified a single-nucleotide polymorphism (SNP) that results in missplicing of the cholecystokinin (CCK) receptor gene and expressing a larger mutated receptor in pancreatic cancer. The purpose of this study was to evaluate the significance and specificity of this SNP as a potential biomarker in patients with pancreatic cancer compared with other gastrointestinal (GI) cancers that also have CCK receptors.

METHODS: DNA was isolated and genotyped for the CCK receptor SNP from frozen tumor tissue from banked specimens of patients with pancreas, gastric, or colon cancer and from human cancer cell lines. Genotype and allelic frequencies were compared between the cancer cohort and two normal control databases using Fisher's exact test and odds ratio (OR). The Kaplan-Meier method was used to estimate the survival for patients with the CCK-B receptor SNP compared with those with the wild-type genotype. Immunohistochemical staining of cancer cells was done to detect the mutated receptor.

RESULTS: Colon and gastric cancer patients had similar genotype frequencies for the CCK receptor SNP as that reported in the normal population. In contrast, the prevalence of the SNP in subjects with pancreatic cancer was twice that of controls and other GI cancers. Survival was adversely affected by the presence of the SNP only in those with pancreatic cancer. Immunoreactivity for the mutated receptor was positive in pancreatic cancer tissues with the SNP but absent in other GI cancers.

CONCLUSIONS: A SNP of the CCK receptor is significantly increased in patients with pancreatic cancer but not in those with other GI malignancies. Therefore, this SNP may be a potential biomarker for pancreatic cancer.

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