Non-steroidal anti-inflammatory drugs and cancer risk in women: Results from the Women's Health Initiative

Abstract

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risks of cancers at several sites in some studies; however, we recently reported no association between their use and total cancer risk in women in a prospective study. Here we examine the association between NSAIDs and total and site-specific cancer incidence in the large, prospective Women’s Health Initiative (WHI). 129,013 women were recruited to participate in the WHI at 40 US clinical centers from 1993 to 1998 and followed prospectively. After 9.7 years of follow-up, 12,998 incident, first primary, invasive cancers were diagnosed. NSAID use was systematically collected at study visits. We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs use and total and site-specific cancer risk. Relative to non-use, consistent use (i.e., use at baseline and year 3 of follow-up) of any NSAID was not associated with total cancer risk (HR 1.00, 95% CI: 0.94–1.06). Results for individual NSAIDs were similar to the aggregate measure. In site-specific analyses, NSAIDs were associated with reduced risks of colorectal cancer, ovarian cancer, and melanoma. Our study confirms a chemopreventive benefit for colorectal cancer in women and gives preliminary evidence for a reduction of the risk of some rarer cancers. NSAIDs’ benefit on cancer risk was limited to specific sites and not evident when total cancer risk was examined. This information may be of importance when NSAIDs are considered as chemopreventive agents.

Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer: a nationwide case–control study

“…In our study, however, we found no effect modification by obesity, and several other studies have also reported similar risk estimates for use of NSAIDs among obese and non-obese women [15,16,18,20,[32][33][34]37]. In fact, the differential effect of aspirin according to body mass index observed in the meta-analysis [6] was primarily driven by the results of two studies [35,36].…”

“…Consistent with [13,17,20,32,[34][35][36]. Among these are some large studies based on prospective data from the Women's Health Initiative [32], the Multiethnic Cohort [20], and the Nurses' Health Study [35]. Other studies, including a meta-analysis [6], have reported nonsignificant [15,16,33,37] or significant [6,18] endometrial cancer risk reductions associated with overall aspirin use.…”

“…Consistent with [13,17,20,32,[34][35][36]. Among these are some large studies based on prospective data from the Women's Health Initiative [32], the Multiethnic Cohort [20], and the Nurses' Health Study [35].…”

“…In both of these studies, data also indicated further risk reductions with increasing duration [18] or frequency [6] of aspirin use. The remaining studies have not found any dose-response relation [16,20,32,[34][35][36][37]. Finally, the association between aspirin use and endometrial cancer risk was evaluated by Cook et al [38,39] in the Women's Health Study, where the 39,876 women were randomized to 100 mg of aspirin or placebo every other day.…”

Aspirin Use and Risk of Breast Cancer: Systematic Review and Meta-analysis of Observational Studies

“…We calculated prediction interval (PI) of summary estimate for the random effects model to depict the uncertainty around the estimate (17). If studies did not report a summary risk estimate for aspirin use, a summary risk estimate was calculated using risk estimates for each of the aspirin use categories (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Interstudy heterogeneity was estimated using a c 2 -based Q test (34), with a P value of <0.10 considered statistically significant (35).…”