Association of single nucleotide polymorphisms of β2-adrenergic receptor gene with clinicopathological features of pancreatic carcinoma

Abstract

β2-Adrenoceptor agonists induce pancreatic cancer occurrence and progression through β2-AR. Polymorphisms in β2-AR gene lead to modified sensitivity to agonists and variable tumorigenic potential. In this study, pancreatic carcinoma and non-neoplastic pancreatic tissues were genotyped at codons 16 and 27 by PCR–restriction fragment length polymorphism and DNA sequencing. Expressions of β2-AR, EGFR, VEGF and MMP-2 were detected by immunohistochemistry. The frequencies of genotypes and alleles at codon 16 between pancreatic carcinoma and non-neoplastic pancreatic tissues showed no difference. The genotype frequencies were associated with TNM grade, lymph node metastasis, and one-year survival rate. The allele G at codon 16 frequently appeared in tumors with high TNM grade, lymph node metastasis, poor prognosis, high expression levels of β2-AR, EGFR, VEGF and MMP-2. The genotype and allele frequencies of codon 27 were not associated with clinicopathological features and down-stream protein expressions. Collectively, SNPs of β2-AR gene at codon 16 were associated with the biological behavior of pancreatic carcinoma. The allele G at codon 16 could facilitate the progression and metastasis of pancreatic carcinoma through elevating vascularization and activating the EGFR pathway. SNPs at codon 16 of β2-AR are new useful biomarkers for predicting biological behavior and survival of pancreatic carcinoma and might be used as a new gene therapeutic target.