Giovannucci E, Pollak M N, Platz E A, Willett W C, Stampfer M J, Majeed N, Colditz G A, Speizer F E, Hankinson S E
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Apr;9(4):345-9.
Insulin-like growth factor-1 (IGF-1) is an important mitogen, and IGF binding protein-3 (IGFBP-3) has opposing effects. Acromegalics, who have abnormally elevated levels of IGF-1, are at increased risk of colorectal tumors. Recent studies have found that IGF-1 levels correlate with risk of prostate cancer and colorectal cancer in men, premenopausal breast cancer in women, and lung cancer in men and women. We examined whether prediagnostic plasma levels of IGF-1 and IGFBP-3 influence risk of colorectal cancer and adenoma in women. From 1989 to 1990, a total of 32,826 women from the Nurses' Health Study provided blood specimens that were archived in liquid nitrogen. During 6 years of follow-up from 1989 to 1994, we documented 79 new cases of colorectal cancer, 90 cases of intermediate/late-stage adenoma (> or =1 cm or tubulovillous/villous histology), and 107 cases of early-stage adenoma (<1 cm and tubular histology). After matching controls (2:1 for cancers and 1:1 for adenomas) to cases by age, month of blood draw, fasting status, and indication for endoscopy (for adenoma controls), plasma IGF-1 and IGFBP-3 levels were measured. Controlling for IGFBP-3 level, relative to women in the low tertile of IGF-1, those in the high tertile were at elevated risk of intermediate/late-stage colorectal neoplasia adenoma [multivariate relative risk (RR), 2.78; 95% confidence interval (CI), 0.76-9.76] and cancer (RR, 2.18; 95% CI, 0.94-5.08). Controlling for IGF-1 level, relative to women in the low tertile of IGFBP-3, women in the high tertile of IGFBP-3 were at lower risk of intermediate/late-stage colorectal adenoma (RR, 0.28; 95% CI, 0.09-0.85) and cancer (RR, 0.28; 95% CI, 0.10-0.83). Neither IGF-1 nor IGFBP-3 had any appreciable relation with early-stage adenoma. These analyses indicate that high levels of circulating IGF-1 and particularly low levels of IGFBP-3 are associated independently with an elevated risk of large or tubulovillous/villous colorectal adenoma and cancer.
胰岛素样生长因子-1（IGF-1）是一种重要的促细胞分裂剂，而胰岛素样生长因子结合蛋白-3（IGFBP-3）则具有相反的作用。肢端肥大症患者的IGF-1水平异常升高，患结直肠癌的风险增加。最近的研究发现，IGF-1水平与男性前列腺癌和结直肠癌、女性绝经前乳腺癌以及男性和女性肺癌的风险相关。我们研究了诊断前血浆IGF-1和IGFBP-3水平是否会影响女性患结直肠癌和腺瘤的风险。1989年至1990年，护士健康研究中的32826名女性提供了血液标本，并保存在液氮中。在1989年至1994年的6年随访期间，我们记录了79例新的结直肠癌病例、90例中/晚期腺瘤（≥1 cm或绒毛状/管状组织学）和107例早期腺瘤（<1 cm且为管状组织学）。在根据年龄、采血月份、空腹状态和内镜检查指征（针对腺瘤对照）将对照（癌症为2:1，腺瘤为1:1）与病例匹配后，测量血浆IGF-1和IGFBP-3水平。在控制IGFBP-3水平的情况下，与IGF-1处于低三分位数的女性相比，处于高三分位数的女性发生中/晚期结直肠肿瘤性腺瘤的风险升高[多变量相对风险（RR）为2.78；95%置信区间（CI）为0.76 - 9.76]，患癌风险也升高（RR为2.18；95%CI为0.94 - 5.08）。在控制IGF-1水平的情况下，与IGFBP-3处于低三分位数的女性相比，IGFBP-3处于高三分位数的女性发生中/晚期结直肠腺瘤的风险较低（RR为0.28；95%CI为0.09 - 0.85），患癌风险也较低（RR为0.28；95%CI为0.10 - 0.83）。IGF-1和IGFBP-3与早期腺瘤均无明显关联。这些分析表明，循环中高水平的IGF-1，尤其是低水平的IGFBP-3，与大的或绒毛状/管状结直肠腺瘤及癌症的风险升高独立相关。
