A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer
A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer
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DOI：
10.1158/1055-9965.epi-07-2686
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发表时间：
2008-04-01
影响因子：
3.8
通讯作者：
Strickler, Howard D.
中科院分区：
文献类型：
--
作者：
Gunter, Marc J.;Hoover, Donald R.;Strickler, Howard D.
肥胖是子宫内膜癌的一个主要危险因素，这种关系被认为在很大程度上是由肥胖妇女中高雌激素水平的流行所解释的。肥胖还与高水平的胰岛素有关，胰岛素是一种已知的有丝分裂原。然而，没有前瞻性研究直接评估胰岛素和/或胰岛素样生长因子-I（IGF-I），一种相关激素，是否与子宫内膜癌相关，同时考虑雌激素水平。因此，我们在妇女健康倡议观察性研究中进行了一项关于子宫内膜癌事件的病例队列研究，该研究是一项前瞻性队列研究，共有93，676名绝经后妇女参加。该研究涉及所有250例事件病例和465例受试者的随机子队列进行比较。在空腹基线血清标本中测量胰岛素、总IGF-I、游离IGF-I、IGF结合蛋白-3、葡萄糖和雌二醇水平。考克斯模型用于评估与子宫内膜癌的相关性，特别是子宫内膜样腺癌，主要的组织学类型（n = 205）。我们的数据显示，在调整年龄和雌二醇后，未使用激素治疗的女性中，胰岛素水平与乳腺样腺癌呈正相关[风险比对比最高与最低四分位数（HRq 4-q1），2.33; 95%置信区间（95%CI），1.13-4.82]。校正年龄、激素治疗使用和雌二醇后，游离IGF-I与类甲状腺腺癌呈负相关（HRq 4-q1，0.53; 95%CI，0.31-0.90）。这两种相关性在超重/肥胖女性中更强，尤其是胰岛素与类胰腺癌之间的相关性（HRq 4-q1，4.30; 95%CI，1.62-11.43）。这些数据表明，高胰岛素血症可能是卵巢样腺癌的一个独立于雌二醇的危险因素。游离IGF-I水平与乳腺样腺癌呈负相关，与先前的横断面数据一致。
Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HRq4-q1), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HRq4-q1, 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HRq4-q1, 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data.