Wolpin BM et al. (2007) Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Res 67: 7923–7928

Insulin-like growth factor binding protein-1 (IGFBP-1) is an inhibitor of insulin-like growth factor-I (IGF-I). IGF-I is highly expressed in pancreatic cancer cell lines; however, previous studies have failed to show an association of this protein with pancreatic cancer. Low plasma levels of IGFBP-1 have been associated with obesity and a sedentary lifestyle, both factors that have been implicated in the development of pancreatic cancer. Wolpin et al. examined the utility of IGFBP-1 as a prognostic factor in pancreatic cancer.

The study included 144 patients with pancreatic cancer and 429 controls matched for age, sex, and smoking and fasting status, who participated in four US prospective cohort studies. After adjusting for risk factors such as plasma IGF-I, IGF-binding protein-3 and C-peptide, subjects with circulating IGFBP-1 levels in the lowest quartile had a relative risk (RR) of pancreatic cancer of 2.07 compared with those in the three highest quartiles. Individuals in the lowest IGFBP-1 quartile who were diagnosed ≥8 years after collection of blood samples had an adjusted RR of 3.47 compared with individuals in the three highest quartiles. The influence of low IGFBP-1 was shown to be greater among never smokers (RR 3.30), participants with nonfasting plasma samples (≤8 hours of fasting; RR 2.69), and among individuals with elevated plasma C-peptide (RR 2.32); however, none of these interactions was statistically significant.

The authors conclude that low circulating levels of IGFBP-1 independently predict the risk of pancreatic cancer, and call for further studies to examine the role of insulin and the IGF axis in this malignancy.