Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8–12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (−4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (−15%; P = 0.018) or 325 mg/day (−28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

中文翻译：

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低剂量和标准剂量阿司匹林对结直肠腺瘤个体 PGE2 生物合成的影响：一项随机临床试验


美国预防服务工作组建议使用低剂量阿司匹林作为某些个体结直肠癌的一级预防。然而，更广泛的实施将需要改进精确的预防方法，以确定最有可能受益的人。 PGE2 的主要尿液代谢物 11α-羟基-9,15-二氧代-2,3,4,5-四去甲-前列腺素-1,20-二酸 (PGE-M) 是结直肠癌风险的生物标志物，但目前尚不清楚阿司匹林是否可以改变有结直肠癌风险的个体中的 PGE-M。最近接受腺瘤切除术且不经常使用阿司匹林或 NSAID 的成年人 (N = 180) 被招募参加一项双盲、安慰剂对照、随机试验，阿司匹林每天服用 81 或 325 毫克，持续 8-12 周。主要结果是通过 LC/MS 测量的干预后尿 PGE-M 变化。共有 169 名参与者提供了配对的尿液样本进行分析。基线 PGE-M 排泄量为 15.9 ± 14.6（平均值 ± SD，ng/mg 肌酐）。阿司匹林显着减少 PGE-M 排泄 (−4.7 ± 14.8)，而安慰剂组则没有减少 (0.8 ± 11.8)（P = 0.015；平均治疗持续时间 = 68.9 天）。与安慰剂相比，每天服用 81 毫克（−15%；P = 0.018）或 325 毫克（−28%；P < 0.0001）的阿司匹林显着降低了 PGE-M 水平。在随机服用 81 毫克/天或 325 毫克/天阿司匹林的受试者中，分别有 40% 和 50% 的受试者的 PGE-M 减少量达到了预期可防止 10% 的受试者复发的阈值。这些结果支持阿司匹林显着降低结直肠癌风险增加患者的 PGE-M 水平升高至与肿瘤复发风险较低一致的水平，并强调 PGE-M 作为精准化学预防生物标志物的潜在效用。 ASPIRED 试验注册号为 NCT02394769。