Lukanova Annekatrin, Lundin Eva, Micheli Andrea, Arslan Alan, Ferrari Pietro, Rinaldi Sabina, Krogh Vittorio, Lenner Per, Shore Roy E, Biessy Carine, Muti Paola, Riboli Elio, Koenig Karen L, Levitz Mortimer, Stattin Pär, Berrino Franco, Hallmans Göran, Kaaks Rudolf, Toniolo Paolo, Zeleniuch-Jacquotte Anne
International Agency for Research on Cancer, Lyon, France.
Int J Cancer. 2004 Jan 20;108(3):425-32. doi: 10.1002/ijc.11529.
Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.
实验和流行病学数据支持性甾体激素在子宫内膜癌发病机制中起作用。研究了诊断前血液中雌二醇、雌酮、睾酮、雄烯二酮、硫酸脱氢表雄酮（DHEAS）和性激素结合球蛋白（SHBG）浓度与子宫内膜癌风险的关联。一项病例对照研究嵌套于美国纽约、瑞典于默奥和意大利米兰的3个队列中。病例为124名患有浸润性子宫内膜癌的绝经后女性。为每个病例选择2名对照，对照与病例在队列、年龄和招募日期上相匹配。仅纳入献血时未使用外源性激素的绝经后女性。通过条件逻辑回归估计比值比（OR）及其95%置信区间（CI）。激素水平最高四分位数相对于最低四分位数的子宫内膜癌OR（95%CI）如下：雌二醇为4.13（1.76 - 9.72），p（趋势）=0.0008；雌酮为3.67（1.71 - 7.88），p（趋势）=0.0007；雄烯二酮为2.15（1.05 - 4.40），p（趋势）=0.04；睾酮为1.74（0.88 - 3.46），p（趋势）=0.06；DHEAS为2.90（1.42 - 5.90），p（趋势）=0.002；SHBG为0.46（0.20 - 1.05），p（趋势）=0.01，上述结果均为调整体重指数、口服避孕药使用情况和激素替代治疗后所得。我们多中心前瞻性研究的结果显示，绝经后女性循环雌激素、雄激素与子宫内膜癌呈强正相关，SHBG水平与子宫内膜癌呈负相关。雄烯二酮和睾酮水平升高对疾病风险的影响似乎主要通过它们转化为雌激素来介导，尽管不能排除雄激素对肿瘤生长的独立作用，尤其是在接近诊断的年份。
