Sonestedt Emily, Borgquist Signe, Ericson Ulrika, Gullberg Bo, Olsson Håkan, Adlercreutz Herman, Landberg Göran, Wirfält Elisabet
Department of Clinical Sciences in Malmö, Research Group in Nutrition Epidemiology, Lund University, Malmo University Hospital, Cancer Research Centre Entrance 72, Building 60 Floor 13, SE-205 02 Malmö, Sweden.
Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3241-51. doi: 10.1158/1055-9965.EPI-08-0393.
Differences in the estrogen receptor (ER) status of tumors may explain ambiguities in epidemiologic studies between the blood concentrations of enterolactone and breast cancer. To our knowledge, the association between enterolactone and ERbeta-defined breast cancer has previously not been examined.
A nested case-control study within the Malmö Diet and Cancer cohort used 366 cases and 733 matched controls to identify the major determinants of plasma enterolactone and to examine the association between enterolactone concentration and breast cancer risk and if this association differs depending on the ERalpha and ERbeta status of tumors. A modified diet history method assessed dietary habits. Time-resolved fluoroimmunoassay determined enterolactone concentrations and immunohistochemistry using tissue microarray determined ER status.
Dietary fiber, as well as fruits and berries, and high-fiber bread showed statistically significant correlations with enterolactone (r, 0.13-0.22). Smoking and obesity were associated with lower enterolactone concentrations. Enterolactone concentrations above the median (16 nmol/L) were associated with reduced breast cancer risk when compared with those below [odds ratio, 0.75; 95% confidence interval (95% CI), 0.58-0.98]. The reduced risk was only observed for ERalpha [positive (+); odds ratio, 0.73; 95% CI, 0.55-0.97] and ERbeta [negative (-)] tumors (odds ratio, 0.60; 95% CI, 0.42-0.84), with significantly different risks for ERbeta (-) and ERbeta (+) tumors (P for heterogeneity = 0.04).
This study supports the suggestion that enterolactone is a biomarker of a healthy lifestyle. The protective association between enterolactone and breast cancer was significantly different between ERbeta (-) and ERbeta (+) tumors and most evident in tumors that express ERalpha but not ERbeta.
肿瘤雌激素受体（ER）状态的差异可能解释了肠内酯血药浓度与乳腺癌之间流行病学研究中的模糊性。据我们所知，此前尚未研究过肠内酯与ERβ定义的乳腺癌之间的关联。
在马尔默饮食与癌症队列中进行的一项巢式病例对照研究，使用366例病例和733例匹配对照来确定血浆肠内酯的主要决定因素，并研究肠内酯浓度与乳腺癌风险之间的关联，以及这种关联是否因肿瘤的ERα和ERβ状态而异。改良的饮食史方法评估饮食习惯。时间分辨荧光免疫测定法测定肠内酯浓度，使用组织微阵列的免疫组织化学法测定ER状态。
膳食纤维以及水果和浆果，还有高纤维面包与肠内酯呈统计学显著相关性（r，0.13 - 0.22）。吸烟和肥胖与较低的肠内酯浓度相关。与低于中位数（16 nmol/L）的浓度相比，高于中位数的肠内酯浓度与降低的乳腺癌风险相关[比值比，0.75；95%置信区间（95%CI），0.58 - 0.98]。仅在ERα[阳性（+）]和ERβ[阴性（-）]肿瘤中观察到风险降低[比值比，0.73；95%CI，0.55 - 0.97]以及[比值比，0.60；95%CI，0.42 - 0.84]，ERβ（-）和ERβ（+）肿瘤的风险有显著差异（异质性P = 0.04）。
本研究支持肠内酯是健康生活方式生物标志物的观点。肠内酯与乳腺癌之间的保护关联在ERβ（-）和ERβ（+）肿瘤之间存在显著差异，并且在表达ERα但不表达ERβ的肿瘤中最为明显。
