胰腺癌患者与对照组之间胆囊收缩素B受体基因型的分布及其对生存的影响。
Distribution of cholecystokinin-B receptor genotype between patients with pancreatic cancer and controls and its impact on survival.
作者信息
Smith Jill P, Whitcomb David C, Matters Gail L, Brand Randall E, Liao Jiangang, Huang Yu-Jing, Frazier Marsha L
机构信息
From the *Department of Medicine, Georgetown University, Washington, DC; †Department of Medicine, Pennsylvania State University, College of Medicine, Hershey; ‡Department of Medicine, University of Pittsburgh; §University of Pittsburgh Medical Center, Pittsburgh; Departments of ∥Biochemistry and Molecular Biology, and ¶Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, PA; and #Department of Epidemiology, University of Texas at MD Anderson Cancer Center, Houston, TX.
出版信息
Pancreas. 2015 Mar;44(2):236-42. doi: 10.1097/MPA.0000000000000263.
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 from a 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.
目的
胆囊收缩素（CCK）和胃泌素通过CCK-B受体（CCK-BR）刺激胰腺癌生长。已鉴定出一种由单核苷酸多态性（SNP）导致的CCK-BR剪接变体。由于该剪接变体受体的第三个细胞内环延长，而该区域参与细胞信号传导和生长，我们推测这种基因变体可能导致这种恶性肿瘤的预后不良和生存期短。
方法
对931例胰腺癌患者的DNA进行CCK-BR基因SNP（C>A；rs1800843）评估。统计分析采用Fisher精确检验比较癌症队列与正常对照之间的基因型和等位基因频率，并使用Cox比例风险模型分析基因型对疾病分期和年龄等因素的依赖性。
结果
与正常队列相比，胰腺癌患者中A等位基因的频率增加（P=0.01123；优势比，2.283）。即使在调整疾病分期后，携带次要等位基因的患者的生存期仍显著短于野生基因型患者（风险比，1.83；P=3.11×10⁻¹¹）。
结论
CCK-BR SNP可预测生存期，应作为胰腺癌高危人群的候选遗传生物标志物进行研究。
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