Toniolo P G, Levitz M, Zeleniuch-Jacquotte A, Banerjee S, Koenig K L, Shore R E, Strax P, Pasternack B S
Department of Environmental Medicine, New York University School of Medicine, NY 10010, USA.
J Natl Cancer Inst. 1995 Feb 1;87(3):190-7. doi: 10.1093/jnci/87.3.190.
Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue.
Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease.
The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5 1/2 years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80 degrees C since sampling.
For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend < .01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend < .01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis.
These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer.
Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life.
有间接证据表明内源性雌激素与女性患乳腺癌风险增加有关，但直接的流行病学支持有限。特别是，仅有少数小型前瞻性研究探讨过这一问题。
我们的目的是评估与两种主要内源性雌激素（雌酮和雌二醇）循环水平相关的乳腺癌风险，这些雌激素水平是在疾病临床发病前测量的。
在一项对14291名35至65岁纽约市女性进行的前瞻性队列研究中，检测了雌激素血清水平与乳腺癌风险之间的关联。这些女性在采血时接受了乳腺癌筛查且未被诊断出患有乳腺癌。在研究的前5.5年中，我们在绝经后组（7063名女性，35509人年）中确定了130例乳腺癌病例。病例组和两倍数量的绝经后对照组被纳入了队列中嵌套的病例对照研究。对自采样后一直保存在-80摄氏度的血清进行了游离雌二醇百分比、与性激素结合球蛋白（SHBG）结合的雌二醇百分比、总雌二醇、雌酮和促卵泡激素的生化分析。
对于总雌二醇四分位数增加的情况，经奎特利指数（体重千克数除以身高米数的平方）调整后的乳腺癌比值比（OR）分别为1.0、0.9、1.8和1.8（趋势P值 = 0.06）；对于雌酮四分位数增加的情况，OR分别为1.0、2.2、3.7和2.5（趋势P值 = 0.06）。对于游离雌二醇（定义为未与蛋白质结合的雌二醇部分）四分位数增加的情况，经奎特利指数调整后的乳腺癌OR分别为1.0、1.4、3.0和2.9（趋势P值 < 0.01）。当我们考虑与SHBG结合的雌二醇百分比时，经奎特利指数调整后的OR分别为1.0、0.70、0.40和0.32（趋势P值 < 0.01），因此表明有很强的保护作用。当分析仅限于在乳腺癌诊断前2年或更长时间采集样本的女性时，这些关联持续存在或变得更强。
这些数据首次在一项大型前瞻性流行病学研究中证实了循环雌激素与乳腺癌风险之间的联系。尽管在所有研究女性中雌激素水平似乎都在正常的常规范围内，但与未患癌症的女性相比，随后患乳腺癌的女性往往显示出更高的雌酮、总雌二醇和游离雌二醇水平，以及更低的与SHBG结合的雌二醇百分比。
增加内源性雌激素产生或降低雌二醇与SHBG结合的因素可能会增加女性在晚年患乳腺癌的风险。
