Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 2012 Feb 1;72(3):696-706. doi: 10.1158/0008-5472.CAN-11-2507. Epub 2011 Dec 5.
Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.
内源性雌激素及其代谢物被认为与绝经前乳腺癌风险相关，但证据有限。我们在护士健康研究 II（NHSII）中进行了一项巢式病例对照研究，检测了 18521 名处于黄体中期的绝经前妇女的 15 种尿液雌激素/雌激素代谢物与乳腺癌风险的关系。1996 年至 1999 年期间，在收集尿液的同时收集了每位妇女的尿液。2005 年 6 月前诊断为乳腺癌的病例（N=247）与每位病例各匹配了 2 位对照（N=485）。采用液相色谱-串联质谱法测量尿液雌激素代谢物，并根据肌酐水平进行了调整。通过多变量条件逻辑回归估计相对风险（RR）和 95%置信区间（CI）。与最低四分位数相比，尿液雌酮和雌二醇水平较高与风险降低显著相关（雌酮 RR：top vs. bottom quartile = 0.52；95%CI，0.30-0.88；雌二醇 RR：top vs. bottom quartile = 0.51；95%CI，0.30-0.86）。尽管无统计学意义，但与 2-和 4-羟基化途径雌激素代谢物也观察到了一般呈反向但非显著的关系。与 16-途径雌激素代谢物无显著关联，而与 17-表雌三醇呈显著正相关（最高 vs. 最低四分位数 RR = 1.74；95%CI，1.08-2.81；P（趋势）= 0.01）。此外，较高的 16-途径/母体雌激素代谢物比值与风险增加显著相关（可比 RR = 1.61；95%CI，0.99-2.62；P（趋势）= 0.04）。除了母体雌激素代谢物/非母体雌激素代谢物（可比 RR = 0.58；95%CI，0.35-0.96；P（趋势）= 0.03）外，其他途径比值与风险无显著关联。这些数据表明，绝经前妇女黄体中期大多数尿液雌激素代谢物浓度与乳腺癌风险无正相关。与母体雌激素代谢物和母体雌激素代谢物/非母体雌激素代谢物比值呈负相关表明，尿液中母体雌激素排泄较高的妇女风险较低。
