Rachael Stolzenberg-Solomon

R.D., Ph.D.

NCI, DCEG, NEB

Senior Investigator

PLCO (Learn more about this study)

2005-0024

Apr 21, 2006

Insulin Resistance-Related Metabolic Markers and Pancreatic Cancer Risk

Obesity, diabetes mellitus, and higher glucose and insulin concentrations have been associated with increased pancreatic cancer risk in observational studies. This proposed nested case-control (200 cases and 400 matched controls) study within the PLCO Trial will be one of the largest to evaluate the insulin secretion and IGF axis hypotheses and will break new ground evaluating adipocytokines and pancreatic cancer risk. The study aims are 1) to determine whether greater insulin secretion and poor glycemic control as measured by high circulating levels of C-peptide and glycosylated hemoglobin are prospectively associated with pancreatic cancer risk, 2) to determine whether adipocytokines that regulate insulin sensitivity and glucose metabolism as measured by circulating levels of adiponectin, leptin, and interleukin-6 (IL-6), and IL-6-dependent hepatic biosynthesis of C-reactive protein (CRP), a marker of systematic chronic inflammation, are associated with pancreatic cancer risk, 3) To determine whether insulin-like growth factors (IGF-I, IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3), a system that is linked to insulin concentrations, are associated with pancreatic cancer. Secondary aims are to 1) to examine differences in risk associations by the interval between blood collection and pancreatic cancer diagnosis and 2) to evaluate with a QC sub-study, the within subject reliability of the biomarkers using two measures on these analytes for 50 control subjects, with blood samples collected at study entry and 1 year thereafter. The results from this study will confirm previous studies and provide insight into the mechanisms by which diabetes, insulin secretion, adiposity, and smoking increase pancreatic cancer risk, and the role of diabetes type 2 in pancreatic cancer development. We also plan collaboration in a consortium of cohorts organized by Dr. Huang (JHU) to study these biomarkers hypotheses across several study populations, including their joint effects on pancreatic cancer risk. The consortium activity is contingent on extramural funding. For the purposes of this submission, our proposal should be judged alone to test for main effects but with further added value, should the consortium be launched.