HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA.
Department of Orthopaedic Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA 02115, USA; Department of Urology, Boston Children's Hospital, Boston, MA 02115, USA.
Eur J Cancer. 2019 May;112:118-126. doi: 10.1016/j.ejca.2018.11.033. Epub 2019 Mar 6.
Statins have demonstrated protection against aggressive/late-stage and/or lethal prostate cancer (PC), but prior studies are limited by small populations, short follow-up and unequal health-care access. Research has not demonstrated that non-statin lipid-lowering medications (NSLLMs) provide a similar benefit, which would support a cholesterol-based mechanism. We sought to rigorously test the hypothesis that cholesterol-lowering drugs affect PC incidence and severity.
A retrospective cohort study was conducted by abstracting prescription and health service records for 249,986 Saskatchewan men aged ≥40 years between January 1, 1990 and December 31, 2014 and comparing first-time statin and NSLLM users with age-matched non-users and glaucoma medication (GM) users for PC incidence, metastases at diagnosis and PC mortality using Cox proportional hazards regression.
In comparing statin users to non-users, a weak association was detected with increased PC incidence (hazard ratio [HR] 1.07, 95% confidence interval [CI]: 1.02-1.12) that disappeared when compared with GM users. Substantial protective associations were observed between statin use and metastatic PC and PC mortality (HRs 0.69, 95% CI: 0.61-0.79 and 0.73, 95% CI: 0.66-0.81, respectively), which were stronger when compared with GM use (HRs 0.52, 95% CI: 0.40-0.68 and 0.51, 95% CI: 0.41-0.63, respectively). Similar associations were found for NSLLM versus GM for metastatic PC (HR 0.57, 95% CI: 0.41-0.79) and PC mortality (HR 0.66, 95% CI: 0.51-0.85).
Our analyses provide one of the more comprehensive findings to date that statins may reduce risk of metastatic PC and PC mortality, and the first to demonstrate that NSLLM have similar effects, supporting a cholesterol-based mechanism.
他汀类药物已被证明可预防侵袭性/晚期和/或致命性前列腺癌（PC），但先前的研究受到研究人群规模小、随访时间短和医疗保健获取不平等的限制。研究并未表明非他汀类降脂药物（NSLLM）具有类似的益处，这将支持基于胆固醇的机制。我们试图严格检验胆固醇降低药物是否会影响 PC 发病和严重程度的假设。
通过提取 1990 年 1 月 1 日至 2014 年 12 月 31 日期间萨斯喀彻温省 40 岁及以上 249986 名男性的处方和健康服务记录，进行了一项回顾性队列研究，并比较了首次使用他汀类药物和 NSLLM 的患者与年龄匹配的非使用者和青光眼药物（GM）使用者的 PC 发病、诊断时转移和 PC 死亡率，使用 Cox 比例风险回归。
与非使用者相比，他汀类药物使用者的 PC 发病风险略有增加（风险比 [HR] 1.07，95%置信区间 [CI]：1.02-1.12），但与 GM 使用者相比，这种关联消失了。与 GM 使用者相比，他汀类药物使用与转移性 PC 和 PC 死亡率之间存在明显的保护关联（HRs 分别为 0.69，95%CI：0.61-0.79 和 0.73，95%CI：0.66-0.81），与 GM 使用者相比，这些关联更强（HRs 分别为 0.52，95%CI：0.40-0.68 和 0.51，95%CI：0.41-0.63）。对于 GM 使用者，NSLLM 与转移性 PC（HR 0.57，95%CI：0.41-0.79）和 PC 死亡率（HR 0.66，95%CI：0.51-0.85）也存在类似的关联。
我们的分析提供了迄今为止更全面的发现之一，即他汀类药物可能降低转移性 PC 和 PC 死亡率的风险，并且首次证明 NSLLM 具有类似的作用，支持基于胆固醇的机制。
