Division of Urologic Surgery and Duke Prostate Center, Department of Surgery, Duke University Medical Center, Box 2626, MSRB-I Room 455B, 571 Research Drive, Durham, NC 27710, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):722-8. doi: 10.1158/1055-9965.EPI-09-1074. Epub 2010 Feb 16.
Cholesterol-lowering drugs known as statins have been reported to have significant anti-inflammatory properties. Given that inflammation may contribute to prostate cancer progression and that statins may reduce the risk for advanced prostate cancer, we investigated whether statin use was associated with reduced intratumoral inflammation in radical prostatectomy (RP) specimens.
Inflammation within index tumors of 236 men undergoing RP from 1996 to 2004 was graded by a single pathologist as grade 0 (absent), 1 (mild: < or =10%), and 2 (marked: >10%). Preoperative statin use was analyzed by grouping subjects as statin users or nonusers. Type and dosage of statin was accounted for using dose equivalents with 20 mg simvastatin as reference. Logistic regression was used to determine the association between statin use and intratumoral inflammation controlling for age, race, body mass index, prostate-specific antigen, year of surgery, clinical stage, pathologic Gleason sum, surgical margin status, extracapsular extension, seminal vesicle invasion, prostate weight, time from prostate biopsy to RP, and nonsteroidal anti-inflammatory drug use.
Preoperative statin use was significantly associated with lower risk for any (grade > or =1) intratumoral inflammation (odds ratio, 0.31; 95% confidence interval, 0.10-0.98; P = 0.047) on multivariable analysis, with doses > or =20 mg simvastatin equivalents being more strongly associated (relative to nonuse; odds ratio, 0.22; 95% confidence interval, 0.06-0.79; P = 0.02).
In a cohort of men undergoing RP, statin use was associated with significantly lower risk of any inflammation within prostate tumors.
Given previous reports that inflammation is associated with advanced prostate cancer, and statin use is associated with decreased prostate cancer progression risk, our findings suggest that inhibition of inflammation within tumors may be a potential mechanism for purported anti-prostate cancer properties of statins.
已知降脂药物他汀类药物具有显著的抗炎特性。鉴于炎症可能导致前列腺癌的进展,而他汀类药物可能降低晚期前列腺癌的风险,我们研究了他汀类药物的使用是否与根治性前列腺切除术(RP)标本中肿瘤内炎症的减少有关。
由一名病理学家对 236 名 1996 年至 2004 年间接受 RP 的男性的指数肿瘤内的炎症进行分级,分为 0 级(不存在)、1 级(轻度:<=10%)和 2 级(明显:>10%)。通过将受试者分为他汀类药物使用者和非使用者来分析术前他汀类药物的使用情况。使用他汀类药物等效剂量来考虑他汀类药物的类型和剂量,以 20mg 辛伐他汀为参考。使用逻辑回归来确定他汀类药物的使用与肿瘤内炎症之间的关联,同时控制年龄、种族、体重指数、前列腺特异性抗原、手术年份、临床分期、病理 Gleason 总和、手术切缘状态、包膜外扩展、精囊侵犯、前列腺重量、从前列腺活检到 RP 的时间和非甾体抗炎药的使用。
多变量分析显示,术前他汀类药物的使用与任何(等级>=1)肿瘤内炎症的风险显著降低相关(比值比,0.31;95%置信区间,0.10-0.98;P=0.047),而使用剂量>=20mg 辛伐他汀等效物的相关性更强(与未使用者相比;比值比,0.22;95%置信区间,0.06-0.79;P=0.02)。
在接受 RP 的男性队列中,他汀类药物的使用与前列腺肿瘤内任何炎症的风险显著降低相关。
鉴于先前有报道称炎症与晚期前列腺癌有关,而他汀类药物的使用与前列腺癌进展风险降低有关,我们的研究结果表明,肿瘤内炎症的抑制可能是他汀类药物所谓的抗前列腺癌特性的潜在机制。