Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer Prev Res (Phila). 2020 Oct;13(10):853-862. doi: 10.1158/1940-6207.CAPR-19-0450. Epub 2020 Jun 24.
Aspirin and statin use may lower the risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the 7-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, and c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker [OR, 5.60; 95% confidence interval (CI), 1.16-27.07], and statin users were more likely to have low CD68, a macrophage marker (OR, 1.63; 95% CI, 0.81-3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk.
阿司匹林和他汀类药物的使用可能降低晚期/致命性前列腺癌的风险,其机制可能是减少前列腺内炎症。为了验证这一假说,我们研究了阿司匹林和他汀类药物的使用与前列腺内炎症的存在和程度,以及特定免疫细胞类型的丰度之间的关系,这些组织取自前列腺癌预防试验安慰剂组的一部分男性的前列腺组织活检。如果男性在基线或 7 年试验期间报告使用过,则将其归类为阿司匹林或他汀类药物使用者。根据试验方案,对研究结束时进行的前列腺活检切片进行评估,无论临床指征如何,都要评估炎症的存在和程度,并对特定免疫细胞类型(CD4、CD8、FoxP3、CD68 和 c-KIT)的标志物进行评分。使用逻辑回归估计药物使用与炎症指标之间的关联,调整了潜在混杂因素的影响。在纳入的 357 名男性中,61%报告使用过阿司匹林,32%报告使用过他汀类药物。炎症的发生率和程度与药物使用无关。然而,与未使用者相比,阿司匹林使用者更可能具有低水平的 FoxP3,这是 T 调节细胞标志物[比值比(OR),5.60;95%置信区间(CI),1.16-27.07],他汀类药物使用者更可能具有低水平的 CD68,这是巨噬细胞标志物(OR,1.63;95%CI,0.81-3.27)。如果这些结果得到证实,这表明这些药物可能改变前列腺的免疫微环境,这可能介导这些药物对晚期/致命性前列腺癌风险的影响。