Insulin-like growth factor-binding protein 3 and incidence of pancreatic cancer in a nested case-control study.

Background: Insulin-like growth factors (IGFs) are potent mitogens and IGF-binding protein 3 (IGFBP3) can regulate IGF activity. To elucidate relationships between IGF-related molecules and risk of pancreatic cancer, we analyzed associations between serum levels of IGF1 and IGFBP3 and incidence of pancreatic cancer in a prospective, nested, case-control study within the Japan Collaborative Cohort study.

Methods: A baseline survey was conducted from 1988 to 1990, during which period blood samples were obtained from 39 242 subjects. Subjects who had been diagnosed with pancreatic cancer by 1997 were regarded as cases. Conditional logistic regression was used to estimate odds ratios (ORs) for the incidence of pancreatic cancer in relation to serum levels of IGF1 and IGFBP3.

Results: This analysis included 72 cases and 216 controls. Free IGFBP3 (estimated as IGFBP3-IGF1) was associated with the risk of pancreatic cancer (P for trends = 0.011), with the third tertile showing the highest risk (OR = 3.42, 95%CI = 1.31-8.91). None of total IGF1, free IGF1 (estimated as IGF1/IGFBP3), or total IGFBP3 were associated with risk of pancreatic cancer. This result remained unchanged in subanalyses of male, female, and older subjects (P for trends = 0.017, 0.030, and 0.007, respectively). When limiting analysis to participants followed for over 2 years, free IGFBP3 was associated with risk of pancreatic cancer (P for trends = 0.025).

Conclusions: Our findings suggest that free IGFBP3 is associated with the risk of pancreatic cancer.