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.

Copyright © January 7, 2010, American Association for Cancer Research
2010