Troisi R, Potischman N, Hoover R N, Siiteri P, Brinton L A
Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892-7374, USA.
Am J Epidemiol. 1997 Sep 15;146(6):476-82. doi: 10.1093/oxfordjournals.aje.a009301.
Elevated insulin levels may explain part of the increased risk of endometrial cancer observed in obese postmenopausal women. Circulating sex hormones and fasting C-peptide levels were measured in sera obtained from 165 postmenopausal endometrial cancer cases accrued between June 1, 1987, and May 15, 1990, from hospitals in Chicago, Illinois; Hershey, Pennsylvania; Irvine and Long Beach, California; Minneapolis, Minnesota; and Winston-Salem, North Carolina, and 180 community and hysterectomy controls. Women with a personal history of diabetes were excluded. Among controls, C-peptide was positively correlated with body mass index (BMI) ((r = 0.44), waist-to-thigh circumference ratio ((r = 0.24), estrone ((r = 0.18), and estradiol ((r = 0.28) (albumin-bound (r = 0.45), and free (r = 0.37)) and negatively correlated with sex hormone-binding globulin (r = -0.48). In age-adjusted analyses, the odds ratios and 95% confidence intervals for tertiles of C-peptide and endometrial cancer were, from lowest to highest: 1.0 (reference), 0.78 (95% confidence interval (CI) 0.43-1.4), and 2.2 (95% CI 1.3-3.7). Further adjustment for BMI substantially attenuated the odds ratios for the highest tertile of C-peptide (odds ratio = 1.2, 95% CI 0.63-2.1), and adjustment for body mass index and other risk factors for endometrial cancer eliminated the association (odds ratio = 1.0, 95% CI 0.55-2.0). In contrast, adjustment for C-peptide had little influence on the magnitude of the positive associations between body mass index (odds ratio for highest vs. lowest tertile, without and with adjustment for C-peptide = 4.1 (95% CI 2.3-7.5) and 3.7 (95% CI 1.9-7.1), respectively) or several steroid hormones and endometrial cancer. These data are not consistent with the hypothesis that the effect of obesity on endometrial cancer risk is mediated through high insulin levels.
胰岛素水平升高可能是肥胖绝经后女性子宫内膜癌风险增加的部分原因。在1987年6月1日至1990年5月15日期间，从伊利诺伊州芝加哥、宾夕法尼亚州好时、加利福尼亚州欧文和长滩、明尼苏达州明尼阿波利斯以及北卡罗来纳州温斯顿 - 塞勒姆的医院收集的165例绝经后子宫内膜癌病例和180例社区及子宫切除对照者的血清中，检测了循环性激素和空腹C肽水平。排除有糖尿病个人史的女性。在对照组中，C肽与体重指数（BMI）（r = 0.44）、腰臀围比（r = 0.24）、雌酮（r = 0.18）和雌二醇（r = 0.28）（白蛋白结合型（r = 0.45）和游离型（r = 0.37））呈正相关，与性激素结合球蛋白呈负相关（r = -0.48）。在年龄调整分析中，C肽三分位数与子宫内膜癌的比值比及95%置信区间，从最低到最高依次为：1.0（参考值）、0.78（95%置信区间（CI）0.43 - 1.4）和2.2（95%CI 1.3 - 3.7）。进一步调整BMI后，C肽最高三分位数的比值比大幅降低（比值比 = 1.2，95%CI 0.63 - 2.1），调整BMI及其他子宫内膜癌危险因素后，这种关联消失（比值比 = 1.0，95%CI 0.55 - 2.0）。相比之下，调整C肽对体重指数（最高与最低三分位数的比值比，未调整和调整C肽后分别为4.1（95%CI 2.3 - 7.5）和3.7（95%CI 1.9 - 7.1））或几种甾体激素与子宫内膜癌之间的正相关强度影响不大。这些数据与肥胖对子宫内膜癌风险的影响是通过高胰岛素水平介导的这一假设不一致。
