Prediagnostic Plasma IGFBP-1, IGF-1 and Risk of Prostate Cancer

Abstract

Insulin-like growth factor (IGF)-1 is associated with a higher risk of prostate cancer. IGF-binding protein (IGFBP)-1, a marker for insulin activity, also binds IGF-1 and inhibits its action. Data on IGFBP-1 and prostate cancer risk are sparse and whether the IGF and insulin axes interact to affect prostate cancer carcinogenesis is unknown. We evaluated the independent and joint influence of prediagnostic plasma levels of IGFBP-1 (fasting) and IGF-1 on risk of prostate cancer among 957 cases and 1,021 controls with fasting levels of IGFBP-1 and 1,709 cases and 1,778 controls with IGF-1 nested within the Health Professionals Follow-up Study. Unconditional logistic regression adjusting for matching factors was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Higher prediagnostic fasting IGFBP-1 levels were associated with lower risk of prostate cancer (highest vs. lowest quartile OR=0.67, 95% CI 0.52-0.86, p(trend)=0.003), which remained similar after adjusting for IGF-1. Prediagnostic IGF-1 was associated with increased risk of prostate cancer (highest vs. lowest quartile OR=1.28, 95% CI=1.05-1.56, p(trend)=0.01). The associations with each marker were primarily driven by lower-grade and non-advanced prostate cancer. Being low in IGFBP-1 and high in IGF-1 did not confer appreciable additional risk (p(interaction)=0.42). In summary, prediagnostic fasting IGFBP-1 may influence prostate cancer carcinogenesis. Being low in IGFBP-1 or high in IGF-1 is sufficient to elevate the risk of prostate cancer.What's new? Increased levels of insulin-like growth factor 1 (IGF-1) in the circulation are linked to an elevated risk of prostate cancer. The bioavailability of IGF-1 is limited, however, by IGF binding protein-1 (IGFBP-1), though little is known about the relationship between IGFBP-1 and prostate cancer. In this prospective case-control study, increased prediagnostic fasting plasma IGFBP-1 levels were found to be associated with a reduced risk of prostate cancer, and the positive association between circulating IGF-1 levels and prostate cancer risk was confirmed. The associations were most significant for low-grade and non-advanced disease.