Kabat G C, Chang C J, Sparano J A, Sepkovie D W, Hu X P, Khalil A, Rosenblatt R, Bradlow H L
Department of Epidemiology and Social Medicine, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA.
Cancer Epidemiol Biomarkers Prev. 1997 Jul;6(7):505-9.
Preliminary studies suggest that the estrogen metabolite 16 alpha-hydroxyestrone is associated with breast cancer, whereas 2-hydroxyestrone is not. However, epidemiological studies evaluating this relationship and taking established risk factors for breast cancer into account are lacking. The purpose of this study was to examine the association of the ratio of the urinary estrogen metabolites (2-hydroxyestrone and 16 alpha-hydroxyestrone) and of the individual metabolites with breast cancer. A spot urine sample, a brief history, and clinical data were collected from breast cancer cases (n = 42) and from women coming to the hospital for a routine mammogram or attending a free breast cancer screening (n = 64). 2-Hydroxyestrone and 16 alpha-hydroxyestrone were measured by enzyme immunoassay, and the estrogen metabolite ratio (EMR; 2-hydroxyestrone:16 alpha-hydroxyestrone) was computed. Cases and controls were similar in terms of age (mean age of cases, 53.8 +/- 15.1 years, versus 54.2 +/- 10.4 years for controls; P = 0.9) and demographics. Mean EMR was not associated with breast cancer overall (1.67 +/- 0.80 versus 1.72 +/- 0.66; P = 0.7). However, in postmenopausal women, the mean EMR was significantly lower in cases compared to controls (1.41 +/- 0.73 versus 1.81 +/- 0.71; P = 0.05). The multivariate adjusted odds ratios for the intermediate and lowest tertiles of the EMR relative to the highest among postmenopausal women were 9.73 (95% confidence interval, 1.27-74.84) and 32.74 (95% confidence interval, 3.36-319.09), respectively. The test for trend was highly significant (P = 0.003). Analyses of the individual metabolites indicated that 16 alpha-hydroxyestrone was a strong risk factor. The EMR did not show any consistent associations with age, race/ethnicity, age at first birth, parity, body mass index, family history of breast cancer, smoking, or alcohol intake. These data suggest a strong, inverse association of the EMR and a strong positive association of 16 alpha-hydroxyestrone with breast cancer in postmenopausal women. Larger studies are needed to confirm these results and to assess the relationship of the EMR and of the individual metabolites with breast cancer, with attention to menopausal status and clinical factors and with adjustment for known breast cancer risk factors.
初步研究表明，雌激素代谢物16α-羟基雌酮与乳腺癌有关，而2-羟基雌酮则不然。然而，缺乏评估这种关系并考虑到已确定的乳腺癌风险因素的流行病学研究。本研究的目的是检验尿雌激素代谢物（2-羟基雌酮和16α-羟基雌酮）的比率以及个体代谢物与乳腺癌之间的关联。收集了乳腺癌患者（n = 42）以及前来医院进行常规乳房X光检查或参加免费乳腺癌筛查的女性（n = 64）的即时尿样、简要病史和临床数据。通过酶免疫测定法测量2-羟基雌酮和16α-羟基雌酮，并计算雌激素代谢物比率（EMR；2-羟基雌酮:16α-羟基雌酮）。病例组和对照组在年龄（病例组平均年龄为53.8±15.1岁，对照组为54.2±10.4岁；P = 0.9）和人口统计学特征方面相似。总体而言，平均EMR与乳腺癌无关（分别为1.67±0.80和1.72±0.66；P = 0.7）。然而，在绝经后女性中，病例组的平均EMR显著低于对照组（分别为1.41±0.73和1.81±0.71；P = 0.05）。绝经后女性中，EMR处于中间三分位数和最低三分位数相对于最高三分位数的多变量调整优势比分别为9.73（95%置信区间为1.27 - 74.84）和32.74（95%置信区间为3.36 - 319.09）。趋势检验具有高度显著性（P = 0.003）。对个体代谢物的分析表明，16α-羟基雌酮是一个强风险因素。EMR与年龄、种族/族裔、初产年龄、产次、体重指数、乳腺癌家族史、吸烟或饮酒量均未显示出任何一致的关联。这些数据表明，绝经后女性中EMR与乳腺癌呈强负相关，16α-羟基雌酮与乳腺癌呈强正相关。需要进行更大规模的研究来证实这些结果，并评估EMR和个体代谢物与乳腺癌的关系，同时关注绝经状态和临床因素，并对已知的乳腺癌风险因素进行调整。
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