Abstract B115: Plasma insulin-like growth factor 1, binding protein-3, and risk of prostate cancer: An update from the Health Professional Follow-up Study 1993–2004

Abstract

Abstract Background: The insulin-like growth factor (IGF) axis plays a role in growth and progression of prostate cancer cells. A pooled analysis concluded that high circulating IGF-1 is associated with an increased risk of prostate cancer. Some studies have indicated that the positive association is observed only for low-grade prostate cancer with a Gleason sum below 7. Results for IGF binding protein 3 (IGFBP-3) are inconclusive. Material and Methods: We previously reported in the Health Professionals Follow-up Study (HPFS) a direct positive association between ELISA-measured plasma IGF-1 and IGFBP-3 and risk of prostate cancer (462 cases diagnosed after providing a blood specimen in 1993, but before February 1998). With additional follow-up through January 31st 2004, and 1331 case-control pairs in total, we were now able to investigate low-grade (Gleason sum <7, n= 635) and high-grade (Gleason sum ≥7, n=515) prostate cancer separately. In addition, we investigated potential effect modification by age at diagnosis, family history of prostate cancer and dietary lycopene, which, beyond acting as an anti-oxidant, may inhibit prostate cancer by interfering with IGF-1 signaling. Matched odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: ORs of total prostate cancer comparing top to bottom quartiles were 1.41 (95% CI 1.12–1.78, p-trend=0.001) for IGF-1 and 1.58 (95% CI 1.24–2.01, p-trend=0.003) for IGFBP-3. These results did not change remarkably when cases diagnosed within the first two years after blood draw were excluded. IGF-1 was more strongly associated with low-grade (OR=1.61 top versus bottom quartile, 95% CI 1.16–2.25, p-trend=0.01), than with high-grade (OR=1.29, 95% CI 0.89–1.88, p-trend-0.12) prostate cancer (p-heterogeneity=0.08). With IGFBP-3, significant positive associations were observed for both low-grade (OR=1.83 top versus bottom quartile, 95% CI 1.29–2.61) and high-grade (OR=1.60, 95% CI 1.08–2.37) prostate cancer (p-heterogeneity=0.84). We did not observe heterogeneous effects of IGF-1 or IGFBP-3 by age at diagnosis (</≥65 years), tomato sauce intake (≤/>2 servings/week) or plasma lycopene (</≥1123 mol/L, corresponding to 75th percentile in controls). The association between IGF-1 and total prostate cancer was slightly stronger among men with positive family of prostate cancer (OR per standard deviation in IGF-1 1.15, 95% CI 1.01–1.31) than in those without family history of prostate cancer (OR 1.06, 95% CI 0.99–1.13, p-interaction=0.03). Conclusion: This large nested case-control study provides further evidence that IGF-1 may be preferentially associated with low-grade prostate cancer. We hypothesize that this observation reflects that high-grade prostate cancers are more autonomous, and, thus, less sensitive to IGF-1 levels than low-grade cancers. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B115.