Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Division of Epidemiology, Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Carcinogenesis. 2018 May 28;39(6):819-825. doi: 10.1093/carcin/bgy050.
The roles of obesity, metabolic dysregulation and systemic inflammation to advance prostate carcinogenesis are unclear. This study investigates metabolic and inflammatory factors in the transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). We prospectively followed 160 men diagnosed with HGPIN at biopsy and therefore at high-risk and clinically monitored for PC. Analyses investigated body mass index (BMI), waist circumference, waist-hip ratio (WHR), height, fat mass, lean mass percent body fat, NSAIDs, statins, metformin, diabetes, hypertension, hypercholesterolemia representing metabolic dysregulation on the risk of a PC diagnosis during follow-up. Systemic inflammation was estimated through measurement of 13 plasma cytokine levels. Statin use was significantly linked with overall PC at follow-up [odds ratio (OR) = 0.45, (0.23, 0.91), P = 0.03], with a somewhat stronger link with high-grade [OR = 0.39, (0.15, 1.04), P = 0.06] PC compared with low-grade PC [OR = 0.50, (0.23, 1.12), P = 0.09]. Non-statin cholesterol-lowering medications, BMI, WHR, diabetes, hypertension and percent body fat were not significantly associated with PC. Although blood IL-12p70, IL-2 and IL-1β levels were significantly lower among statin users, inflammatory markers were not significantly linked with PC and did not explain the observed relationship between statins and lower PC risk. In summary, this prospective study of HGPIN patients at high risk for PC finds that statin use was significantly associated with reduced risk of PC detection at follow-up. Systemic markers of inflammation did not mediate this association, suggesting that statins affect PC progression through alternative pathways.
肥胖、代谢失调和全身炎症在促进前列腺癌发生中的作用尚不清楚。本研究调查了从高级别前列腺上皮内瘤变（HGPIN）到前列腺癌（PC）的过渡中的代谢和炎症因素。我们前瞻性地随访了 160 名在活检时被诊断为 HGPIN 的男性，因此处于高危状态，并进行了临床监测以发现 PC。分析调查了体重指数（BMI）、腰围、腰臀比（WHR）、身高、脂肪量、瘦体重百分比、体脂肪百分比、非甾体抗炎药（NSAIDs）、他汀类药物、二甲双胍、糖尿病、高血压、高胆固醇血症，代表代谢失调，用于预测随访期间 PC 诊断的风险。通过测量 13 种血浆细胞因子水平来评估全身炎症。他汀类药物的使用与随访时的总 PC 显著相关[比值比（OR）=0.45，（0.23，0.91），P=0.03]，与高级别 PC [OR=0.39，（0.15，1.04），P=0.06]的相关性略强于低级别 PC [OR=0.50，（0.23，1.12），P=0.09]。非他汀类降胆固醇药物、BMI、WHR、糖尿病、高血压和体脂肪百分比与 PC 无显著相关性。尽管他汀类药物使用者的血液白细胞介素-12p70、白细胞介素-2 和白细胞介素-1β水平显著降低，但炎症标志物与 PC 无显著相关性，也不能解释他汀类药物与较低的 PC 风险之间的关系。总之，这项针对高危 PC 的 HGPIN 患者的前瞻性研究发现，他汀类药物的使用与随访时 PC 检出率的降低显著相关。全身炎症标志物与这种相关性没有关系，这表明他汀类药物通过替代途径影响 PC 的进展。
