Case-control study of endogenous steroid hormones and endometrial cancer
Case-control study of endogenous steroid hormones and endometrial cancer
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DOI：
10.1093/jnci/88.16.1127
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发表时间：
1996-08-21
期刊：
影响因子：
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通讯作者：
Lurain, JR
中科院分区：
文献类型：
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作者：
Potischman, N;Hoover, RN;Lurain, JR
背景：已确定的子宫内膜癌危险因素通过单一的病因学途径起作用，即暴露于相对较高水平的非对立雌激素(在缺乏孕激素的情况下为雌激素)。然而，只有少数研究直接解决了这个问题。目的：我们评估了绝经前和绝经后妇女发生子宫内膜癌的风险与类固醇激素和性激素结合球蛋白(SHBG)循环水平的关系。在调整了其他已知危险因素后，对激素的独立影响进行了评估。方法：分析中使用的数据来自于在美国五个地理区域进行的病例对照研究。仅在1987年6月1日至1990年5月15日期间新诊断的病例。病例患者年龄20-74岁，按年龄、种族和地理区域与对照组相匹配。社区对照对象为随机数字拨号法(年龄20~)和卫生筹资管理局档案中(大于或等于65岁)。其他因良性疾病而行子宫切除术的对照组受试者来自参与中心。排除在访谈后6个月内报告使用外源性雌激素或口服避孕药的妇女，绝经前妇女中有68例患者和107例对照对象，绝经后妇女中有208例患者和209例对照对象。激素分析是在手术前对病例患者或子宫切除对照组的血液样本进行的。在控制了匹配变量和潜在混杂因素后，使用非条件Logistic回归分析估计了优势比(OR)和95%可信区间(CI)。所有P值均为双侧。结果：经其他因素调整后，在绝经前和绝经后妇女中，高雄烯二酮水平分别使风险增加3.6倍和2.8倍(趋势P值分别为0.01和0.001)。与其他激素组分相关的风险因更年期状况而异。在绝经后妇女中，风险降低与高SHBG水平相关，并在调整了肥胖和其他因素后持续存在(OR=0.51；95%CI=0.27-0.95)。高雌酮水平与风险增加相关(OR=3.8；95%CI=2.2-6.6)，但调整其他危险因素(特别是体重指数)后，这种影响减弱(OR=2.2；95%CI=1.2-4.4)。白蛋白结合雌二醇(E(2))作为生物可利用度的标志，在调整其他因素后仍是一个重要的危险因素(OR=2.0；95%CI=1.0~3.9)。相反，在绝经前妇女中，高浓度的总E(2)、游离E(2)和白蛋白结合E(2)与增加风险无关。在绝经前和绝经后的人群中，与肥胖和脂肪分布相关的风险不受激素调整的影响。结论：高水平的内源性雌激素与子宫内膜癌的风险增加有关，但它们与其他危险因素的独立性并不符合所有子宫内膜癌危险因素共同的潜在生物途径。意义：进一步的研究应集中在肥胖和体脂分布相关风险的替代内分泌机制，以及绝经前和绝经后疾病中与雄烯二酮相关的风险增加的生物学相关性。
Background: It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. Purpose: We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. Methods: The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases mere newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects greater than or equal to 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. Results: High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E(2)), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E(2) were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. Conclusion: High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate.Implications: Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.