Distribution of cholecystokinin-b receptor genotype between patients with pancreatic cancer and controls and its impact on survival

Objective: Cholecystokinin (CCK) and gastrin stimulate growth of pancreatic cancer through the CCK-B receptor (CCK-BR). A splice variant of the CCK-BR that results froma single nucleotide polymorphism(SNP) has been identified. Because the splice variant receptor has an extended third intracellular loop, an area involved in cell signaling and growth,we hypothesized that this genetic variant could contribute to the poor prognosis and short survival of this malignancy. Methods: DNA from 931 patients with pancreatic cancer was evaluated for the SNP (C > A; rs1800843) in the CCK-BR gene. For statistical analysis, the Fisher exact test was used to compare the genotype and allele frequency between the cancer cohort and normal controls and the dependence of genotype on factors, such as stage of disease and age, was analyzed using Cox proportional hazards models.Results: Compared to the normal cohort, the frequency of the A-allele in pancreatic cancer subjects was increased (P = 0.01123; odds ratio, 2.283). Even after adjustment for stage of disease, survival of subjects with the minor allele was significantly shorter than those with the wild-genotype (hazard ratio, 1.83; P = 3.11 × 10^?11).Conclusions: The CCK-BR SNP predicts survival and should be studied as a candidate genetic biomarker for those at risk of pancreatic cancer.