Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
J Natl Cancer Inst. 2021 Jul 1;113(7):841-851. doi: 10.1093/jnci/djab009.
Prior epidemiological and intervention studies have not been able to separate independent effects of dose, timing, and duration of aspirin use in colorectal cancer (CRC) chemoprevention. We examined aspirin-based CRC chemoprevention according to timing in the Nurses' Health Study and Health Professionals Follow-Up Study.
The exposures include cumulative average dose and total duration of aspirin use in more than 10 years before follow-up started (remote period) and in the immediate 10 years before follow-up started (recent period). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for exposures and CRC risk.
Aspirin use of longer than 10 years before follow-up started (HR = 0.88, 95% CI = 0.83 to 0.94) per 5-year increment and the immediate 10 years before follow-up started (HR = 0.90, 95% CI = 0.84 to 0.96) were similarly important in CRC chemoprevention, though a 5-year lag was required for a clear benefit in the recent period. In the remote period, the association was not dose dependent; compared with less than 0.5 standard-dose (325 mg) tablets per week; hazard ratios were 0.78 (95% CI = 0.63 to 0.98), 0.81 (95% CI = 0.72 to 0.91), and 0.74 (95% CI = 0.64 to 0.86) for doses of 0.5 to less than 1.5, 1.5 to less than 5, and 5 and more tablets per week, respectively. However, there was dose dependency in the recent period (with respective HR = 0.91, 95% CI = 0.79 to 1.06; HR = 0.87, 95% CI = 0.77 to 0.98; and HR = 0.76, 95% CI = 0.64 to 0.91).
A suggestive benefit necessitates at least 6-10 years and most clearly after approximately 10 years since initiation of aspirin. Remote use and use within the previous 10 years both contribute independently to decrease risk, though a lower dose may be required for a benefit with longer term use.
先前的流行病学和干预研究未能将阿司匹林剂量、时间和使用持续时间在结直肠癌（CRC）化学预防中的独立作用分开。我们根据护士健康研究和健康专业人员随访研究中的时间检查了基于阿司匹林的 CRC 化学预防。
暴露包括在随访开始前超过 10 年的累积平均剂量和总持续时间（远程期）和随访开始前的最近 10 年（近期）。使用 Cox 模型估计暴露和 CRC 风险的风险比（HR）和 95%置信区间（CI）。
在随访开始前超过 10 年的阿司匹林使用（每 5 年增加 0.88，95%CI = 0.83 至 0.94）和随访开始前最近 10 年的使用（HR = 0.90，95%CI = 0.84 至 0.96）同样重要，尽管在近期需要 5 年的滞后才能明显受益。在远程期，这种关联与剂量无关；与每周少于 0.5 标准剂量（325mg）的阿司匹林相比，HR 分别为 0.78（95%CI = 0.63 至 0.98）、0.81（95%CI = 0.72 至 0.91）和 0.74（95%CI = 0.64 至 0.86）。剂量分别为每周 0.5 至少于 1.5 片、1.5 至少于 5 片和 5 片及以上。然而，近期存在剂量依赖性（分别为 HR = 0.91，95%CI = 0.79 至 1.06；HR = 0.87，95%CI = 0.77 至 0.98；和 HR = 0.76，95%CI = 0.64 至 0.91）。
至少需要 6-10 年才能产生明显的益处，最明显的是在开始使用阿司匹林后约 10 年。远程使用和最近 10 年内的使用都有助于独立降低风险，尽管长期使用可能需要较低的剂量才能受益。
