摘要

PURPOSE:Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms.
EXPERIMENTAL DESIGN:Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically significant disease, and by ERG and PTEN status. In an exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue.
RESULTS:During 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76; 95% confidence interval (CI), 0.60-0.96] but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40; 95% CI, 0.19-0.87) but not PTEN-intact cancers (HR, 1.18; 95% CI, 0.95-1.48; P heterogeneity = 0.01). Associations did not differ by ERG. Inflammation and immune pathways were enriched in normal prostate tissue of statin ever (n = 10) versus never users (n = 103).
CONCLUSIONS:Molecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk. These findings support a potential causal association and could inform selection of relevant biomarkers for statin clinical trials.

译文

目的: 他汀类药物与侵袭性前列腺癌的风险较低有关,但致死性前列腺癌尚未得到充分研究,其作用机制尚不清楚。我们在卫生专业人员随访研究 (HPFS) 中前瞻性地检查了他汀类药物和致命前列腺癌的风险,测试了与分子亚型的关联,并整合了基因表达谱来确定假定的机制。
实验设计: 我们的研究包括 44,126 名男性无癌症 1990年,随后是 2014年的前列腺癌发病率,他汀类药物的使用记录在两年一次的问卷中。我们使用多变量 Cox 回归来检查他汀类药物与总体前列腺癌风险之间的关系,通过临床显著疾病的测量,以及通过 ERG 和 PTEN 状态。在一项探索性分析中,年龄调整基因集富集分析确定了肿瘤和邻近正常前列腺组织中富集的他汀类药物相关途径。
结果: 在 24 年的随访中,诊断出 6,305 例前列腺癌,801 例 (13%) 致命 (诊断时转移或随访时转移/致命)。相对于从未/过去的使用,目前他汀类药物的使用与致命前列腺癌的风险呈负相关 [HR,0.76; 95% 置信区间 (CI),0.60-0.96],但不是总体疾病。我们发现 PTEN 无效癌症的风险有很强的反向关联 (HR,0.40; 95% CI,0.19-0.87),但 PTEN 不完整癌症的风险 (HR,1.18; 95% CI, 0.95-1.48; P 异质性 = 0.01)。ERG 没有不同的关联。炎症和免疫途径在正常前列腺组织中富集他汀类药物 (n = 10),而从未使用者 (n = 103)。
结论: 分子肿瘤分类确定 PTEN 和炎症/免疫激活是连接他汀类药物与低致死性前列腺癌风险的潜在机制。这些发现支持了一种潜在的因果关联,并可以为他汀类药物临床试验的相关生物标志物的选择提供信息。

Statin

内分泌 抑制剂 治疗药物
概述  :  

他汀类药物,也被称为HMG-CoA还原酶抑制剂,是一类降低血脂的药物,可以降低心血管疾病高危人群的疾病和死亡率。它们是最常见的降低胆固醇的药物。 他汀类药物的形式多种多样,其中包括阿托伐他汀,氟伐他汀,洛伐他汀,匹伐他汀,普伐他汀,瑞舒伐他汀和辛伐他汀。还可以使用他汀类药物和另一种药物(例如依泽替米贝/辛伐他汀)的几种组合制剂。 临床应用 他汀类药物通常用于降低胆固醇水平并降低与动脉粥样硬化有关的疾病的风险

statin   美 /ˈstætn/

释    义   n. 他汀类;抑制素

               n. (Statin)人名;(俄)斯塔京

例    句   Statin drugs lower cholesterol.他汀类药物还可以降低血液胆固醇水平。

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