女性健康倡议观察性研究中的循环雌激素与绝经后卵巢癌风险
Circulating Estrogens and Postmenopausal Ovarian Cancer Risk in the Women's Health Initiative Observational Study.
作者信息
Trabert Britton, Brinton Louise A, Anderson Garnet L, Pfeiffer Ruth M, Falk Roni T, Strickler Howard D, Sliesoraitis Sarunas, Kuller Lewis H, Gass Margery L, Fuhrman Barbara J, Xu Xia, Wentzensen Nicolas
机构信息
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
出版信息
Cancer Epidemiol Biomarkers Prev. 2016 Apr;25(4):648-56. doi: 10.1158/1055-9965.EPI-15-1272-T. Epub 2016 Feb 5.
BACKGROUND
Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS).
METHODS
We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years.
RESULTS
Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors.
CONCLUSIONS
Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers.
IMPACT
These findings further support the heterogeneous etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 648-56. ©2016 AACR.
背景
激素和生殖因素与卵巢癌的发生有关，但很少有研究探讨循环雌激素和雌激素代谢产物与卵巢癌风险之间的关联。在妇女健康倡议（WHI）观察性研究（OS）的一项巢式病例对照研究中，我们评估了绝经后女性血清雌激素和雌激素代谢产物水平是否与卵巢癌风险相关。
方法
我们从参加WHI-OS且基线时未使用绝经激素的女性中选取了所有169例符合条件的上皮性卵巢癌病例和412例匹配对照。通过液相色谱/串联质谱法测量15种雌激素和雌激素代谢产物的基线水平。使用逻辑回归分析总体以及按组织学亚型（浆液性/非浆液性）分层的与卵巢癌风险的关联。从血清采集到癌症诊断的平均时间为6.9年。
结果
总体而言，我们观察到雌酮水平较高的女性存在适度的卵巢癌风险关联[比值比（95%置信区间）第5五分位数（Q）5与Q1相比：1.54（0.82 - 2.90），P趋势 = 0.05]，以及2 - 甲氧基雌酮和4 - 甲氧基雌酮代谢产物[分别为2.03（1.06 - 3.88），P趋势 = 0.02；1.86（0.98 - 3.56），P趋势 = 0.01]。雌激素和雌激素代谢产物的关联因组织学亚型而异。与浆液性肿瘤的关联普遍为无关联，而雌酮[2.65（1.09 - 6.45），P趋势 = 0.01，P异质性 = 0.04]、未结合雌二醇[2.72（1.04 - 7.14），P趋势 = 0.03，P异质性 = 0.02]以及许多2 - 、4 - 和16 - 途径代谢产物与非浆液性肿瘤呈正相关。
结论
我们的研究提供了新的分子数据，表明母体雌激素和几种雌激素代谢产物与非浆液性卵巢癌有关联。
影响
这些发现进一步支持了卵巢癌病因的异质性。《癌症流行病学、生物标志物与预防》；25（4）；648 - 56。©2016美国癌症研究协会。
Zotero 插件