MRC Centre for Causal Analysis in Translational Epidemiology, University of Bristol, Bristol, United Kingdom.
Cancer Res. 2012 Jan 15;72(2):503-15. doi: 10.1158/0008-5472.CAN-11-1601. Epub 2011 Nov 21.
Circulating insulin-like growth factor-I (IGF-I) has been studied extensively in prostate cancer, but there is still little information about IGFs and IGF-binding proteins (IGFBP) in cancers detected by the prostate-specific antigen (PSA) test. Here, we report the findings of a U.K.-based case-control study to investigate circulating IGFs and IGFBPs in PSA-detected prostate cancer with regard to their potential associations with different cancer stages or grades. PSA testing was offered to 110,000 men aged 50 to 69 years from 2002 to 2009. Participants with an elevated level of PSA (≥3.0 ng/mL) underwent prostate biopsy and measurements of blood serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 obtained at recruitment. We found that serum levels of IGF-II (OR per SD increase: 1.16; 95% CI: 1.08-1.24; P(trend) < 0.001), IGFBP-2 (1.18; 1.06-1.31; P(trend) < 0.01) and IGFBP-3 (1.27; 1.19-1.36; P(trend) < 0.001), but not IGF-I (0.99; 0.93-1.04; P(trend) = 0.62), were associated with PSA-detected prostate cancer. After controlling for IGFBP-3, IGF-II was no longer associated (0.99; 0.91-1.08; P(trend) = 0.62) and IGF-I was inversely associated (0.85; 0.79-0.91; P(trend) < 0.001) with prostate cancer. In addition, no strong associations existed with cancer stage or grade. Overall, these findings suggest potentially important roles for circulating IGF-II, IGFBP-2, and IGFBP-3 in PSA-detected prostate cancer, in support of recent in vitro evidence. Although our findings for IGF-I agree with previous results from PSA screening trials, they contrast with positive associations in routinely detected disease, suggesting that reducing levels of circulating IGF-I might not prevent the initiation of prostate cancer but might, nonetheless, prevent its progression.
循环胰岛素样生长因子-I（IGF-I）在前列腺癌中已被广泛研究，但关于前列腺特异性抗原（PSA）检测到的癌症中的 IGFs 和 IGF 结合蛋白（IGFBP）的信息仍然很少。在这里，我们报告了一项基于英国的病例对照研究的结果，该研究旨在调查 PSA 检测到的前列腺癌中循环 IGFs 和 IGFBPs 的情况，以探讨它们与不同癌症阶段或分级的潜在关联。2002 年至 2009 年，向 110,000 名 50 至 69 岁的男性提供 PSA 检测。PSA 水平升高（≥3.0ng/ml）的参与者接受前列腺活检，并在招募时测量血清 IGF-I、IGF-II、IGFBP-2 和 IGFBP-3。我们发现 IGF-II 血清水平（每 SD 增加的 OR：1.16；95%CI：1.08-1.24；P（趋势）<0.001）、IGFBP-2（1.18；1.06-1.31；P（趋势）<0.01）和 IGFBP-3（1.27；1.19-1.36；P（趋势）<0.001），但不是 IGF-I（0.99；0.93-1.04；P（趋势）=0.62）与 PSA 检测到的前列腺癌相关。在控制 IGFBP-3 后，IGF-II 不再相关（0.99；0.91-1.08；P（趋势）=0.62），而 IGF-I 呈负相关（0.85；0.79-0.91；P（趋势）<0.001）与前列腺癌相关。此外，与癌症阶段或分级没有很强的关联。总的来说，这些发现表明循环 IGF-II、IGFBP-2 和 IGFBP-3 在 PSA 检测到的前列腺癌中可能具有重要作用，支持最近的体外证据。尽管我们 IGF-I 的研究结果与之前的 PSA 筛查试验结果一致，但与常规检测到的疾病的阳性关联形成对比，这表明降低循环 IGF-I 水平可能不会阻止前列腺癌的发生，但仍可能阻止其进展。
