Serum Insulin-Like Growth Factor Axis and the Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis

Abstract

Objective: To investigate the association between serum concentration of insulin-like growth factor (IGF) and the risk of pancreatic cancer (PaC). Methods: We identified eligible studies in Medline and EMBASE databases (no reference trials from 2014 to 2016) in addition to the reference lists of original studies and review articles on this topic. A summary of relative risks with 95% confidence intervals (CI) was calculated using a random-effects model. The heterogeneity between studies was assessed using Cochran Q and I2 statistics. Results: Ten studies (seven nested case-control studies and three retrospective case-control studies) were selected as they met our inclusion criteria in this meta-analysis. All these studies were published between 1997 and 2013. The current data suggested that serum concentrations of IGF-I, IGF-II and insulin-like growth factor binding protein-3 (IGFBP-3)in addition to the IGF-I/IGFBP-3 ratio were not associated with an increased risk of PaC (Summary relative risks (SRRs) = 0.92, 95% CI: 0.67–1.16 for IGF-I; SRRs = 0.84, 95% CI: 0.54–1.15 for IGF-II; SRRs = 0.93, 95% CI: 0.69–1.17 for IGFBP-3; SRRs = 0.97, 95% CI: 0.71–1.23 for IGF-I/IGFBP-3 ratio). There was no publication bias in the present meta-analysis. Conclusion: Serum concentrations of IGF-I, IGF-II, IGFBP-1 and IGFBP-3 as well as the IGF-I/IGFBP-3 ratio were not associated with increased risk of PaC.

PACAP and PAC1 receptor expression in pancreatic ductal carcinoma

“…Overexpression of epidermal growth factor (EGF) occurs in the majority of ductal adenocarcinomas of the pancreas and is associated with poorer prognosis (44–46). The increased insulin-like growth factor expression has been found to be correlated with increased risk of pancreatic cancer (47). There is a continuous, urgent need for novel diagnostic markers for pancreatic cancer (48).…”

Insulin-like growth factor 1 and insulin-like growth factor binding protein 2 serum levels as potential biomarkers in differential diagnosis between chronic pancreatitis and pancreatic adenocarcinoma in reference to pancreatic diabetes

“…the results showed for the first time that serum IGF-1, IGF-2, IGFBP-1, and IGFBP-3 concentrations as well as the IGF-1/IGFBP-3 ratio were not associated with risk of PDAC. Sub-group analysis also did not show any significant associations [ 15 ].…”

“…IGF-1 plays a role in the regulation of β-cell mass and the regulation of insulin secretion and sensitivity [ 14 ]. Insulin could stimulate hepatic IGF-1 synthesis and suppress hepatic IGFBP-1 synthesis in the liver, which could lead to an increase in the serum concentration of IGF-1 [ 15 ]. IGF-1 and the IGF-1 receptors are highly expressed on the surface of pancreatic cancer cell lines, which initiate intracellular signalling transduction associated with proliferation, invasion, and expression of mediators of angiogenesis [ 16 ].…”

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation

“…Alternatively, chemotherapy or chemoradiotherapy is still an available therapeutic option, in particular for patients who suffer from local unresectable or advanced metastatic tumors. 6 …”