Schoen Robert E, Weissfeld Joel L, Kuller Lewis H, Thaete F Leland, Evans Rhobert W, Hayes Richard B, Rosen Clifford J
Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA.
Gastroenterology. 2005 Aug;129(2):464-75. doi: 10.1016/j.gastro.2005.05.051.
BACKGROUND & AIMS: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer.
Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements.
Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0-2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1-3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2-3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3-6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0-5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1-4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk.
Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.
胰岛素和胰岛素样生长因子-I（IGF-I）影响细胞增殖、分化和凋亡，是结直肠癌（CRC）的潜在危险因素。内脏肥胖可能通过高胰岛素血症也与CRC风险相关。我们评估了胰岛素、IGF-I、胰岛素样生长因子结合蛋白（IGFBP）3和内脏脂肪组织（VAT）在患有腺瘤性息肉（结直肠癌的前驱病变）的受试者中的关系。
参与者为在前列腺、肺、结直肠和卵巢（PLCO）癌症筛查试验中接受筛查性乙状结肠镜检查（FSG）的无症状受试者。受试者接受单层计算机断层扫描以测量VAT，并进行血清空腹胰岛素、IGF-I和IGFBP-3测量。
共纳入458名受试者，其中202名受试者患有腺瘤，70名患有高级别腺瘤。与对照组相比，腺瘤患者的IGF-I（P = 0.02）、IGF-I/IGFBP-3比值（P = 0.003）和胰岛素（P = 0.02）显著升高。在使用性别特异性四分位数切点的未调整逻辑回归分析中，与IGF-I四分位数1相比，四分位数4的受试者（优势比[OR]=1.7；[95%置信区间：1.0 - 2.9]，Ptrend = 0.03）、IGF-I/IGFBP-3比值（OR = 1.9 [95%置信区间：1.1 - 3.3]，Ptrend = 0.01）和胰岛素（OR = 2.1 [95%置信区间：1.2 - 3.6]，Ptrend = 0.04）患腺瘤的风险增加。当将病例组限制为高级别腺瘤时，这种效应更为明显：IGF-I（OR = 2.8 [95%置信区间：1.3 - 6.2]，Ptrend = 0.006）、IGF-I/IGFBP-3比值（OR = 2.3，[95%置信区间：1.0 - 5.2]，Ptrend = 0.04）和胰岛素（OR = 2.3 [95%置信区间：1.1 - 4.9]，Ptrend = 0.14）。内脏脂肪组织与腺瘤风险无关。
IGF-I水平、IGF-I/IGFBP-3比值和胰岛素与腺瘤相关，与高级别腺瘤的相关性更强。这些数据支持胰岛素和IGF-I可能促成腺瘤性息肉发生和进展的假说。
