Abstract
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.