Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
Breast Cancer Res Treat. 2013 Jun;139(3):801-9. doi: 10.1007/s10549-013-2586-y. Epub 2013 Jun 13.
Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses' Health Study II cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95 % confidence intervals (CI). Compared to women with enterolactone concentrations ≤4 nmol/L, the multivariate-adjusted RRs for breast cancer were 1.18 (95 % CI 0.86-1.62), 0.91 (95 % CI 0.66-1.25), and 0.96 (95 % CI 0.70-1.33) for women with enterolactone levels in the second to the fourth quartiles, respectively; P trend = 0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51 % lower breast cancer risk compared to those in the lowest category (95 % CI 0.27-0.91); P trend = 0.02. No association was observed among women with high-follicular estradiol levels (≥47 pg/mL), (comparable RR = 1.39, 95 % CI 0.73-2.65; P interaction = 0.02). We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low-follicular estradiol levels, suggesting that enterolactone may be important in a low-estrogen environment. This should be confirmed in future studies.
木脂素是植物源性植物雌激素，具有雌激素和抗雌激素特性，可能对乳腺癌的发生具有重要作用。回顾性研究观察到，循环肠内酯浓度较高与乳腺癌风险降低有关，肠内酯浓度是木脂素摄入的生物标志物，但前瞻性研究的结果存在矛盾。为了前瞻性地研究这种相关性，我们在护士健康研究 II 队列中，针对主要为绝经前女性的 802 例乳腺癌病例和 802 例匹配对照者，测量了血浆肠内酯水平。我们使用条件逻辑回归和多分类逻辑回归模型，调整了已知的乳腺癌危险因素，计算了相对风险 (RR) 和 95%置信区间 (CI)。与肠内酯浓度≤4nmol/L 的女性相比，肠内酯浓度处于第二至第四四分位的女性患乳腺癌的多变量调整 RR 分别为 1.18(95%CI 0.86-1.62)、0.91(95%CI 0.66-1.25)和 0.96(95%CI 0.70-1.33)；趋势检验 P 值=0.60。按雌激素和孕激素受体状态定义的肿瘤结果相似。在卵泡雌激素水平低于中位数(<47pg/mL)的绝经前女性中，肠内酯水平最高类别的女性患乳腺癌的风险比最低类别的女性低 51%(95%CI 0.27-0.91)；趋势检验 P 值=0.02。在卵泡雌激素水平较高(≥47pg/mL)的女性中未观察到相关性(可比 RR=1.39，95%CI 0.73-2.65；P 交互作用=0.02)。我们在一项针对美国女性的大型巢式病例对照研究中，未观察到血浆肠内酯与乳腺癌风险之间存在总体相关性。然而，在卵泡雌激素水平较低的绝经前女性中观察到显著的负相关，表明肠内酯在低雌激素环境中可能很重要。这应该在未来的研究中得到证实。
