BACKGROUND: Somatostatin (SST) inhibited cell proliferation and negatively regulated the release of growth hormones by means of specific receptors (SSTR). Genetic variation in SSTR had been associated with risk of human cancers but had never been investigated in pancreatic cancer. METHODS: In this retrospective study the SSTR5 gene in paired tumor and blood samples from 33 pancreatic adenocarcinoma patients using the Sanger method were sequenced. Three single nucleotide polymorphisms (SNPs) in samples from 863 patients with pancreatic ductal adenocarcinoma and 876 healthy controls using the TaqMan method were analyzed. The associations between gene polymorphisms and pancreatic cancer risk and survival were analyzed by multivariate logistic regression and Cox proportional hazard models, respectively. RESULTS: No somatic mutations were identified, but 3 nonsynonymous SSTR5 SNPs (P109S, L48M, and P335L) in pancreatic tumors were identified. The SSTR5 P109S variant allele was associated with a 1.62-fold increased risk of pancreatic cancer (95% confidence interval [CI]: 1.08-2.43, P = 0.019). Furthermore, the SSTR5 L48M AC variant and smoking had a joint effect on pancreatic cancer risk (p(interaction) = 0.035). The odds ratios (95% confidence intervals) were 0.58 (0.34-0.97), 1.49 (1.18-1.89), and 2.27 (1.35-3.83) for the variant genotype alone, smoking alone, and both factors, respectively, compared with no factors. Finally, SSTR5 P335L CC and P109S CC combined were associated with lower overall survival durations in patients with resectable disease. CONCLUSIONS: These data suggest that SSTR5 genetic variants play a role in pancreatic cancer development and progression.
BACKGROUND:Somatostatin (SST) inhibited cell proliferation and negatively regulated the release of growth hormones by means of specific receptors (SSTR). Genetic variation in SSTR had been associated with risk of humancancers but had never been investigated in pancreatic cancer. METHODS: In this retrospective study the SSTR5 gene in paired tumor and blood samples from 33 pancreatic adenocarcinomapatients using the Sanger method were sequenced. Three single nucleotide polymorphisms (SNPs) in samples from 863 patients with pancreatic ductal adenocarcinoma and 876 healthy controls using the TaqMan method were analyzed. The associations between gene polymorphisms and pancreatic cancer risk and survival were analyzed by multivariate logistic regression and Cox proportional hazard models, respectively. RESULTS: No somatic mutations were identified, but 3 nonsynonymous SSTR5 SNPs (P109S, L48M, and P335L) in pancreatic tumors were identified. The SSTR5 P109S variant allele was associated with a 1.62-fold increased risk of pancreatic cancer (95% confidence interval [CI]: 1.08-2.43, P = 0.019). Furthermore, the SSTR5 L48M AC variant and smoking had a joint effect on pancreatic cancer risk (p(interaction) = 0.035). The odds ratios (95% confidence intervals) were 0.58 (0.34-0.97), 1.49 (1.18-1.89), and 2.27 (1.35-3.83) for the variant genotype alone, smoking alone, and both factors, respectively, compared with no factors. Finally, SSTR5 P335L CC and P109S CC combined were associated with lower overall survival durations in patients with resectable disease. CONCLUSIONS: These data suggest that SSTR5 genetic variants play a role in pancreatic cancer development and progression.
Authors: Andrew G Renehan; Marcel Zwahlen; Christoph Minder; Sarah T O'Dwyer; Stephen M Shalet; Matthias Egger Journal: Lancet Date: 2004-04-24 Impact factor: 79.321
Authors: Guisheng Zhou; Jim Sinnett-Smith; Shi-He Liu; Juehua Yu; James Wu; Robbi Sanchez; Stephen J Pandol; Ravinder Abrol; John Nemunaitis; Enrique Rozengurt; F Charles Brunicardi Journal: Front Physiol Date: 2014-06-25 Impact factor: 4.566