Estrogen metabolism and breast cancer risk among postmenopausal women: a casecohort study within B∼FIT
Estrogen metabolism and breast cancer risk among postmenopausal women: a casecohort study within B∼FIT
复制标题
DOI：
10.1093/carcin/bgt367
复制
发表时间：
2014-02-01
期刊：
影响因子：
4.7
通讯作者：
Brinton, Louise A.
中科院分区：
文献类型：
--
作者：
Dallal, Cher M.;Tice, Jeffrey A.;Brinton, Louise A.
尽管循环雌激素升高与绝经后乳腺癌风险增加有关，但关于雌激素代谢在乳腺癌发生中的作用知之甚少。我们在骨折干预试验的乳腺和骨骼随访中进行了一项病例对照研究，以评估随访期间诊断的407例乳腺癌病例和496例女性的子队列中的血清雌激素和雌激素代谢产物（EM）。1992 - 93年，妇女完成了基线调查问卷并提供了血液样本。使用考克斯比例风险回归估计风险比（HR）和95%置信区间（CI），根据地理位置和试验参与状态进行校正。采用液相色谱-串联质谱法测定血清EM浓度。将EM（五分位数，Q）作为代谢途径（C-2、C-4或C-16）和比率单独分析。循环雌二醇升高与乳腺癌风险增加相关（HRQ 5vsQ 1 1.86; 95%CI：1.192.90; P趋势0.04）。2-羟基化途径（HRQ 5vsQ 1 0.69; 95%CI：0.461.05; P趋势0.01）和4-羟基化途径（HRQ 5vsQ 1 0.61; 95%CI：0.400.93; P趋势0.004）与母体雌激素（雌二醇和雌酮）的比值升高与风险呈负相关。2/16-羟基化途径的比例较高与风险降低相关（HRQ 5vsQ 1 0.60; 95% CI：0.400.90; P趋势0.002）。母体雌激素的2-或4-羟基化增加可能降低绝经后乳腺癌的风险。分析代谢途径可能有助于阐明雌激素代谢在乳腺癌发生中的作用。
Although elevated circulating estrogens are associated with increased postmenopausal breast cancer risk, less is known regarding the role of estrogen metabolism in breast carcinogenesis. We conducted a casecohort study within the Breast and Bone Follow-up to the Fracture Intervention Trial to assess serum estrogens and estrogen metabolites (EMs) in 407 incident breast cancer cases diagnosed during follow-up and a subcohort of 496 women. In 199293, women completed a baseline questionnaire and provided blood samples. Hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for geography and trial participation status, were estimated using Cox proportional hazard regression. Serum concentrations of EMs were measured by liquid chromatographytandem mass spectrometry. EMs (quintiles, Q) were analyzed individually, as metabolic pathways (C-2, -4 or -16) and as ratios. Elevated circulating estradiol was associated with increased breast cancer risk (HRQ5vsQ1 1.86; 95% CI: 1.192.90; P trend 0.04). An elevated ratio of the 2-hydroxylation pathway (HRQ5vsQ1 0.69; 95% CI: 0.461.05; P trend 0.01) and 4-hydroxylation pathway (HRQ5vsQ1 0.61; 95% CI: 0.400.93; P trend 0.004) to parent estrogens (estradiol and estrone) was inversely associated with risk. A higher ratio of the 2/16-hydroxylation pathways was associated with reduced risk (HRQ5vsQ1 0.60; 95% CI: 0.400.90; P trend 0.002). Increased 2- or 4-hydroxylation of parent estrogens may lower risk of postmenopausal breast cancer. Analyses of metabolic pathways may help elucidate the role of estrogen metabolism in breast carcinogenesis.