Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Cancer Epidemiol Biomarkers Prev. 2017 Oct;26(10):1549-1557. doi: 10.1158/1055-9965.EPI-17-0503. Epub 2017 Jul 28.
We leveraged two trials to test the hypothesis of an inflammation-prostate cancer link prospectively in men without indication for biopsy. Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study biopsy performed per protocol that was negative for cancer and who subsequently enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were eligible. We selected all 100 cases and sampled 200 frequency-matched controls and used PCPT end-of-study biopsies as "baseline." Five men with PSA > 4 ng/mL at end-of-study biopsy were excluded. Tissue was located for 92 cases and 193 controls. We visually assessed inflammation in benign tissue. We estimated ORs and 95% confidence intervals (CI) using logistic regression adjusting for age and race. Mean time between biopsy and diagnosis was 5.9 years. In men previously in the PCPT placebo arm, 78.1% of cases ( = 41) and 68.2% of controls ( = 85) had at least one baseline biopsy core (∼5 evaluated per man) with inflammation. The odds of prostate cancer ( = 41 cases) appeared to increase with increasing mean percentage of tissue area with inflammation, a trend that was statistically significant for Gleason sum <4+3 disease ( = 31 cases; vs. 0%, >0-<1.8% OR = 1.70, 1.8-<5.0% OR = 2.39, ≥5% OR = 3.31, = 0.047). In men previously in the finasteride arm, prevalence of inflammation did not differ between cases (76.5%; = 51) and controls (75.0%; = 108). Benign tissue inflammation was positively associated with prostate cancer. This first prospective study of men without biopsy indication supports the hypothesis that inflammation influences prostate cancer development. .
我们利用两项试验前瞻性地检验了非前列腺活检指征男性中炎症与前列腺癌关联的假说。符合条件的是：根据协议在研究结束时进行了活检且结果为阴性但随后又参加了硒和维生素 E 防癌试验（SELECT）的前列腺癌预防试验（PCPT）参与者。我们选择了所有 100 例病例，并对 200 例频数匹配对照进行了抽样，将 PCPT 研究结束时的活检作为“基线”。排除了 5 例在研究结束时活检前列腺特异性抗原（PSA）>4ng/ml 的男性。共定位到 92 例病例和 193 例对照的组织。我们对良性组织中的炎症进行了直观评估。使用 logistic 回归模型，通过调整年龄和种族，对病例和对照进行了优势比（OR）和 95%置信区间（CI）的估计。在活检和诊断之间的平均时间为 5.9 年。在 PCPT 安慰剂组的男性中，78.1%（41 例）的病例和 68.2%（85 例）的对照至少有一个基线活检核心（每个男性约评估 5 个核心）存在炎症。前列腺癌（41 例）的发病几率似乎随着炎症组织面积的平均百分比增加而增加，对于 Gleason 评分<4+3 疾病（31 例），这种趋势具有统计学意义（0%、>0-<1.8%OR=1.70、1.8-<5.0%OR=2.39、≥5%OR=3.31， = 0.047）。在接受非那雄胺治疗的男性中，病例（76.5%，51 例）和对照（75.0%，108 例）之间炎症的发生率没有差异。良性组织炎症与前列腺癌呈正相关。这是第一项针对无活检指征男性的前瞻性研究，支持了炎症影响前列腺癌发展的假说。
