Prediagnostic levels of C-peptide, IGF-I, IGFBP-1,-2 and-3
Prediagnostic levels of C-peptide, IGF-I, IGFBP-1,-2 and-3
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DOI：
10.1002/ijc.11544
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发表时间：
2004-01-10
影响因子：
6.4
通讯作者：
Kaaks, R
中科院分区：
文献类型：
--
作者：
Lukanova, A;Zeleniuch-Jacquotte, A;Kaaks, R
与慢性高胰岛素血症相关的疾病，如肥胖、非胰岛素依赖型糖尿病和多囊卵巢综合征，与子宫内膜癌风险增加有关。血浆IGF-1水平升高和IGF结合蛋白水平降低已被证明与富裕社会常见的几种癌症类型的风险增加有关。我们首次在一项前瞻性研究中调查了C肽（胰腺胰岛素产生的标志物）、IGF-1、IGFBP-1、-2和-3诊断前血液浓度与子宫内膜癌风险的关系。在纽约（美国）、Ume（a）over circle（瑞典）和米兰（意大利）的3个队列中进行了一项病例对照研究。它包括166名原发性浸润性子宫内膜癌妇女和315名匹配的对照组，其中44名病例和78名对照组受试者在招募时均为绝经前。子宫内膜癌风险随着C肽水平的增加而增加（p（趋势）= 0.0002），对于最高的五分位数，比值比（OR）高达4.76 [95%置信区间（CI）= 1.91-11.8]。在调整BMI和其他混杂因素后，这种相关性仍然存在[前五分位数的OR = 4.40（1.65-11.7）]。IGFBP-1水平与子宫内膜癌呈负相关[p（趋势）= 0.002;上五分位数的OR = 0.30（0.15-0.62）]，但调整混杂因素后，这种相关性减弱并失去统计学意义[p（趋势）= 0.06;上五分位数的OR = 0.49（0.22-1.07）]。风险与IGF-1，IGFBP-2和IGFBP-3水平无关慢性高胰岛素血症，如循环C肽增加所反映的，与子宫内膜癌风险增加有关。通过改变生活方式或药物治疗，降低慢性高胰岛素血症的患病率，有望预防子宫内膜癌。(C)2003 Wiley-Liss，Inc.
Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-1 and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-1, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Ume (a) over circle (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (p(trend) = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [p(trend) = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [p(trend) = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-1, IGFBP-2 and IGFBP-3 Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer. (C) 2003 Wiley-Liss, Inc.