Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

中文翻译：

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结直肠癌患者阿司匹林和其他非甾体抗炎药使用时间与肿瘤标志物和存活率的关系

目的 定期使用阿司匹林与提高结直肠癌 (CRC) 患者的生存率有关。然而，与生存相关的使用阿司匹林和其他非甾体抗炎药 (NSAID) 获益最大的结直肠癌发生时间和亚型尚不清楚。患者和方法 总共有 2,419 名年龄在 18 至 74 岁之间且在 1997 年至 2008 年间被诊断出患有侵袭性结直肠癌的患者，这些患者来自美国、加拿大和澳大利亚的基于人群的癌症登记处。在研究登记和 5 年随访时进行了详细的流行病学调查问卷。生存结果是通过与国家死亡登记处的联系完成的。还评估了 BRAF 和 KRAS 突变状态、微卫星不稳定性和 CpG 岛甲基化表型。Cox 比例风险回归用于估计总生存率 (OS) 和 CRC 特异性生存率的风险比 (HR) 和 95% CI。结果自诊断后中位随访 10.8 年，观察到 381 例死亡（100 例为 CRC）。与未使用阿司匹林的患者相比，诊断后仅使用阿司匹林的患者具有更有利的 OS（HR，0.75；95% CI，0.59 至 0.95）和 CRC 特异性生存率（HR，0.44；95% CI，0.25 至 0.71），尤其是在那些开始使用阿司匹林的患者中阿司匹林的使用（OS：HR，0.64；95% CI，0.47 至 0.86；CRC 特异性生存：HR，0.40；95% CI，0.20 至 0.80）。诊断后使用任何 NSAID 与 OS 之间的关联因 KRAS 突变状态而异（Pinteraction = .01）。诊断后使用任何 NSAID 仅与 KRAS 野生型肿瘤参与者的 OS 改善相关（HR，0.60；95% CI，0.46 至 0. 80），但不在 KRAS 突变肿瘤患者中（HR，1.24；95% CI，0.78 至 1.96）。结论 在长期 CRC 幸存者中，CRC 诊断后定期使用 NSAIDs 与 KRAS 野生型肿瘤患者的生存率提高显着相关。