Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
Cancer Epidemiol Biomarkers Prev. 2019 Nov;28(11):1845-1852. doi: 10.1158/1055-9965.EPI-19-0597. Epub 2019 Aug 6.
Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts.
We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors.
There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; = 0.37). We did not observe heterogeneity by histotype ( = 0.53), and there was no evidence of effect modification by body mass index ( = 0.82), aspirin use ( = 0.59), or smoking ( = 0.14).
Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes.
Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.
经常使用阿司匹林可能通过阻断环氧化酶来降低卵巢癌风险，导致前列腺素（包括前列腺素 E2 [PGE2]）表达降低。我们评估了三个前瞻性队列中较高的 PGE-M（前列腺素 E2 的尿液生物标志物）是否与卵巢癌风险增加有关。
我们进行了巢式病例对照研究，该研究纳入了护士健康研究（NHS）、NHSII 和上海女性健康研究。我们的分析包括 1996 年至 2015 年间诊断出的 304 例上皮性卵巢癌病例和 600 名匹配对照。我们使用 LC/MS 结合肌酐归一化法测量尿液中的 PGE-M。每个研究的测量值均经过重新校准以达到共同标准。我们使用条件逻辑回归估计 OR 和 95%置信区间（CI），并按四分位数对 PGE-M 水平进行建模。多变量模型根据卵巢癌危险因素进行调整。
在 PGE-M 水平处于最高四分位与最低四分位的女性中，尿液 PGE-M 水平与卵巢癌风险之间没有关联（OR=0.80；95%CI，0.51-1.27； = 0.37）。我们没有观察到按组织类型（ = 0.53）存在异质性，也没有证据表明体重指数（ = 0.82）、阿司匹林使用（ = 0.59）或吸烟（ = 0.14）存在效应修饰。
诊断前尿液 PGE-M 水平与卵巢癌风险无显著相关性。需要更大的样本量来考虑更适度的相关性，并评估特定肿瘤亚型的相关性。
全身前列腺素水平似乎与卵巢癌风险没有密切关联。未来对阿司匹林使用与卵巢癌风险的研究应考虑局部前列腺素和非前列腺素依赖机制。
