Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115.
Cancer Prev Res (Phila). 2014 Jan;7(1):33-41. doi: 10.1158/1940-6207.CAPR-13-0224. Epub 2013 Nov 26.
Multiple myeloma is a lethal malignancy with an unknown etiology and no prevention strategy. Aspirin inhibits several pathways mediated by NF-κB, COX-2, or their targets that are important in multiple myeloma pathogenesis. We conducted prospective analyses in the Health Professionals Follow-up Study and Nurses' Health Study cohorts to examine whether regular aspirin use influences multiple myeloma risk. We used biennially updated data to characterize aspirin use from baseline through a cancer diagnosis, death, or 2008. We applied a 4-year lag in exposure classification to diminish the influence of preclinical multiple myeloma on aspirin use habits. We obtained HRs and 95% confidence intervals (CI) from multivariable proportional hazard models to assess the association of aspirin use with multiple myeloma risk. We tested for trend across increasing quantity and duration of use. During 2,395,458 person-years, we confirmed 328 incident multiple myeloma diagnoses, including 265 with prospective information on typical aspirin dose and frequency. Participants with a cumulative average of ≥5 adult strength (325 mg) tablets per week had a 39% lower multiple myeloma risk than nonusers (HR; 95% CI, 0.61, 0.39-0.94; tablets per week, Ptrend = 0.06). Persons with ≥11 years of continuous regular aspirin use also had a lower multiple myeloma risk (HR; 95% CI, 0.63, 0.41-0.95; duration, Ptrend = 0.17). The associations appeared stronger in men than in women, possibly reflecting gender differences in aspirin use patterns. This prospective study of aspirin use and multiple myeloma supports an etiologic role for aspirin-inhibited (i.e., NF-κB- or COX-2 mediated) pathways. The utility of aspirin for multiple myeloma chemoprevention warrants further evaluation.
多发性骨髓瘤是一种致命的恶性肿瘤,其病因不明,也没有预防策略。阿司匹林可抑制 NF-κB、COX-2 或其靶点介导的多种途径,这些途径在多发性骨髓瘤发病机制中非常重要。我们在健康专业人员随访研究和护士健康研究队列中进行了前瞻性分析,以研究常规使用阿司匹林是否会影响多发性骨髓瘤的风险。我们使用每两年更新的数据来描述从基线到癌症诊断、死亡或 2008 年期间的阿司匹林使用情况。我们采用 4 年的暴露分类滞后来减少临床前多发性骨髓瘤对阿司匹林使用习惯的影响。我们应用多变量比例风险模型获得 HR 和 95%置信区间(CI),以评估阿司匹林使用与多发性骨髓瘤风险的关联。我们检测了使用量和使用时间增加的趋势。在 2395458 人年期间,我们确认了 328 例多发性骨髓瘤病例,其中 265 例有典型阿司匹林剂量和频率的前瞻性信息。与非使用者相比,累积平均每周使用≥5 片成人剂量(325mg)阿司匹林的患者多发性骨髓瘤风险降低 39%(HR:95%CI,0.61,0.39-0.94;每周片数,Ptrend=0.06)。连续使用阿司匹林≥11 年的患者多发性骨髓瘤风险也较低(HR:95%CI,0.63,0.41-0.95;持续时间,Ptrend=0.17)。这些关联在男性中似乎比女性更强,这可能反映了性别在阿司匹林使用模式上的差异。这项关于阿司匹林使用与多发性骨髓瘤的前瞻性研究支持阿司匹林抑制(即 NF-κB 或 COX-2 介导)途径在病因学中的作用。阿司匹林在多发性骨髓瘤化学预防中的作用值得进一步评估。