Regular Aspirin Use and Risk of Multiple Myeloma: A Prospective Analysis in the Health Professionals Follow-up Study and Nurses' Health Study

Abstract

Multiple myeloma is a lethal malignancy with an unknown etiology and no prevention strategy. Aspirin inhibits several pathways mediated by NF-kB, 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, P trend ¼ 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, P trend ¼ 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-kB-or COX-2 mediated) pathways. The utility of aspirin for multiple myeloma chemoprevention warrants further evaluation. Cancer Prev Res; 7(1); 33-41. Ó2013 AACR.

Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study

“…6 However, little is known about predictors of progression of MGUS to MM. 7 Previous studies reported that serum M-protein concentration ≥1·5 g/dL, immunoglobulin (Ig) subtype other than IgG, an abnormal serum-free light-chain ratio, 3, 8 and reduced levels of one or two non-involved Ig isotypes 9 were risk factors for progression. In addition, IgM MGUS does not typically transform into MM, but instead is associated with the development of Waldenstrom macroglobulinemia and other B-cell non-Hodgkin lymphomas.…”

A computational model of MGUS progression to Multiple Myeloma identifies optimum screening strategies and their effects on mortality

“…Furthermore, metformin is associated with a reduced progression of MGUS to MM, potentially delaying MM by four years in type-2 diabetics with MGUS (8). Reduced risk is also associated with regular use of aspirin (7). Although causal relationships of these associations, as well as molecular mechanisms, are uncertain, these findings suggest that pharmacological and other interventions have the potential to reduce the risk of progression from MGUS to MM.…”

“…Recent advances suggest that the rate of progression to MM can be altered by therapeutic interventions (7,8). For example, obesity-a modifiable risk factor for MM-is associated with increased risk (9)(10)(11).…”

Cancer Chemoprevention

“…35 A prospective study of aspirin use and multiple myeloma supported an etiologic role for aspirin-inhibited pathways mediated by NF-κB or COX-2 and warranted further evaluation of aspirin for multiple myeloma chemoprevention. 36 Solaraze ® is a gel effective for the treatment of actinic keratosis (AK) that contains diclofenac sodium as the active agent. Although the cancer chemopreventive mechanism of this agent is unknown, a study on the chemopreventive action of diclofenac in lung cancer induced in female Wistar rats indicated that its effects are mediated by the induction of apoptosis.…”