Severi Gianluca, Morris Howard A, MacInnis Robert J, English Dallas R, Tilley Wayne D, Hopper John L, Boyle Peter, Giles Graham G
Cancer Epidemiology Centre, Cancer Council Victoria, 1 Rathdowne Street, Carlton, Victoria 3053, Australia.
Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1137-41. doi: 10.1158/1055-9965.EPI-05-0823.
Some recent epidemiologic studies have failed to confirm positive associations between insulin-like growth factor-I (IGF-I) and the risk of prostate cancer observed in earlier studies but have reported suggestive evidence for a positive association between IGF-binding protein-3 (IGFBP-3) and prostate cancer risk, a result contradicting the earlier assumption that high levels of IGFBP-3 would be protective against prostate cancer. We tested the association between IGF-I and IGFBP-3 and prostate cancer risk by measuring the two peptides in plasma samples collected at baseline in a prospective cohort study of 17,049 men. We used a case-cohort design, including 524 cases diagnosed during a mean of 8.7 years follow-up and a randomly sampled subcohort of 1,826 men. The association between each peptide level and prostate cancer risk was tested using Cox models adjusted for country of birth and alcohol consumption. The risk of prostate cancer was not associated with baseline levels of IGF-I or the molar ratio IGF-I/IGFBP-3 (all odds ratios are between 0.82 and 1.08; P(trend) > or = 0.2), whereas the risk increased with baseline levels of IGFBP-3 (P(trend) = 0.008), the hazard ratio (HR) associated with a doubling of the concentration of IGFBP-3 being 1.70 (95% confidence interval, 1.15-2.52). The HR for quartile 4 relative to quartile 1 of IGFBP-3 was 1.49 (95% confidence interval, 1.11-2.00). The HRs did not differ by tumor aggressiveness or age at onset (all Ps > or = 0.4). In our study, high levels of IGFBP-3 but not IGF-I were associated with an increased risk of prostate cancer.
一些近期的流行病学研究未能证实早期研究中观察到的胰岛素样生长因子-I（IGF-I）与前列腺癌风险之间的正相关关系，但报告了一些提示性证据，表明胰岛素样生长因子结合蛋白-3（IGFBP-3）与前列腺癌风险之间存在正相关，这一结果与早期认为高水平IGFBP-3对前列腺癌具有保护作用的假设相矛盾。在一项对17049名男性进行的前瞻性队列研究中，我们通过测量基线时采集的血浆样本中的这两种肽，来检验IGF-I和IGFBP-3与前列腺癌风险之间的关联。我们采用病例队列设计，包括在平均8.7年的随访期间诊断出的524例病例，以及随机抽取的1826名男性组成的子队列。使用针对出生国家和饮酒情况进行调整的Cox模型，检验每种肽水平与前列腺癌风险之间的关联。前列腺癌风险与IGF-I的基线水平或IGF-I/IGFBP-3摩尔比无关（所有比值比均在0.82至1.08之间；P趋势≥0.2），而风险随IGFBP-3的基线水平增加（P趋势=0.008），IGFBP-3浓度翻倍相关的风险比（HR）为1.70（95%置信区间，1.15 - 2.52）。IGFBP-3第四四分位数相对于第一四分位数的HR为1.49（95%置信区间，1.11 - 2.0）。HR在肿瘤侵袭性或发病年龄方面无差异（所有P值≥）。在我们的研究中，高水平的IGFBP-3而非IGF-I与前列腺癌风险增加相关。 （注：原文中“所有Ps >或 = 0.4”和“所有P值≥”这里表述似乎不太完整准确，可能影响理解，但按要求未做修改）
