Kim Sangmi, Campbell Jeff, Yoo Wonsuk, Taylor Jack A, Sandler Dale P
Medical College of Georgia, Department of Medicine, Section of Hematology/Oncology, Augusta University Georgia Cancer Center, Augusta, Georgia.
Institute of Public and Preventive Health - Data Coordinating Center, Augusta University, Augusta, Georgia.
Cancer Epidemiol Biomarkers Prev. 2017 Mar;26(3):383-388. doi: 10.1158/1055-9965.EPI-16-0556. Epub 2016 Nov 18.
Prostaglandin E (PGE) induces aromatase expression in adipose tissue, leading to increased estrogen production that may promote the development and progression of breast cancer. However, few studies have simultaneously investigated systemic levels of PGE and estrogen in relation to postmenopausal breast cancer risk. Here, we determined urinary estrogen metabolites (EM) using mass spectrometry in a case-cohort study (295 incident breast cancer cases and 294 subcohort members), and using linear regression estimated the effect of urinary levels of a major PGE metabolite (PGE-M) on EMs. HRs for the risk of developing breast cancer in relation to PGE-M and EMs were compared between Cox regression models with and without mutual adjustment. PGE-M was a significant predictor of estrone (E1), but not estradiol (E2) levels in multivariable analysis. Elevated E2 levels were associated with an increased risk of developing breast cancer [HR, 1.54; 95% confidence interval (CI), 1.01-2.35], and this association remained unchanged after adjustment for PGE-M (HR, 1.52; 95% CI, 0.99-2.33). Similarly, elevated levels of PGE-M were associated with increased risk of developing breast cancer (HR, 2.01; 95% CI, 1.01-4.29), and this association was only nominally changed after consideration of E1 or E2 levels. Urinary levels of PGE-M and estrogens were independently associated with future risk of developing breast cancer among these postmenopausal women. Increased breast cancer risk associated with PGE-M might not be fully explained by the estrogens-breast cancer association alone but also by additional effects related to inflammation. .
前列腺素E（PGE）可诱导脂肪组织中芳香化酶的表达，导致雌激素生成增加，这可能会促进乳腺癌的发生和发展。然而，很少有研究同时调查PGE和雌激素的全身水平与绝经后乳腺癌风险之间的关系。在此，我们在一项病例队列研究（295例新发乳腺癌病例和294名队列成员）中使用质谱法测定尿雌激素代谢物（EM），并使用线性回归估计主要PGE代谢物（PGE-M）的尿水平对EM的影响。在有和没有相互调整的Cox回归模型之间，比较了与PGE-M和EM相关的患乳腺癌风险的HR。在多变量分析中，PGE-M是雌酮（E1）水平的显著预测因子，但不是雌二醇（E2）水平的预测因子。E2水平升高与患乳腺癌的风险增加相关[HR，1.54；95%置信区间（CI），1.01 - 2.35]，在调整PGE-M后，这种关联保持不变（HR，1.52；95%CI，0.99 - 2.33）。同样，PGE-M水平升高与患乳腺癌的风险增加相关（HR，2.01；95%CI，1.01 - 4.29），在考虑E1或E2水平后，这种关联仅略有变化。在这些绝经后女性中，PGE-M和雌激素的尿水平与未来患乳腺癌的风险独立相关。与PGE-M相关的乳腺癌风险增加可能不能完全由雌激素与乳腺癌的关联来解释，还可能与炎症相关的其他影响有关。
