Prediagnosis Circulating Insulin-Like Growth Factors and Pancreatic Cancer Survival
Prediagnosis obesity and diabetes are associated with survival from pancreatic cancer, but the underlying mechanisms have not been characterized. Because both are associated with dysregulation in circulating insulin-like growth factor (IGF) levels, we evaluated the associations of prediagnosis IGF levels (IGF-I, IGF-II) and IGF binding protein 3 (IGFBP-3) with pancreatic cancer survival.
Participants were subjects enrolled in the intervention arm of the PLCO Cancer Screening Trial who developed exocrine pancreatic cancer during follow-up (N = 178, 116 men and 67 women). Participants provided blood samples at enrollment, before cancer diagnosis. Cox proportional hazards regression model, adjusted for confounders was used to investigate associations of IGF biomarkers with pancreatic cancer survival. Because of the well-documented, gender-specific differences in circulating IGF biomarkers, and differential associations of IGF biomarkers with mortality, we evaluated associations separately among males and females.
Median survival was 172 days. Higher IGF-II and IGFBP-3 levels were associated with pancreatic cancer survival among males but not among females. The hazard ratios (HR) of death among men in the highest tertiles of IGF-II and IGFBP-3 compared with men in the lowest tertiles were 0.40 (95% confidence interval (CI) 0.23–0.71, p < 0.01) and 0.59 (95% CI 0.35–0.97, p = 0.10), respectively. There were no statistically significant associations between IGF-I concentrations, IGF-I/IGFBP-3, and pancreatic cancer survival.
Higher prediagnosis circulating IGF-II and IGFBP-3 levels are associated with better pancreatic cancer survival among men but not women. A greater understanding of how IGF signaling is related to pancreatic cancer survival could have utility in improving pancreatic cancer prognosis.
Adetunji T. Toriola is supported by the Siteman Cancer Center, Barnes-Jewish Hospital Foundation and Washington University School of Medicine Faculty Diversity Award. The funding sources have no roles in the study design, collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.
The authors declare no potential conflicts of interest.
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