Use of Non-Steroidal Anti-Inflammatory Drugs and Prostate Cancer Risk: A Population-Based Nested Case-Control Study

Mahmud, Salaheddin M.; Franco, Eduardo L.; Turner, Donna; Platt, Robert W.; Beck, Patricia; Skarsgard, David; Tonita, Jon; Sharpe, Colin; Aprikian, Armen

doi:10.1371/journal.pone.0016412

Cited by 51 publications

(50 citation statements)

References 40 publications

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“…Although our results are similar to those that reported aspirin amount and duration of intake (9), and other studies found no evidence of aspirin dose-effect (7, 30-33) or frequency-effect (31, 34, 35) relationship, the inability to evaluate for a dose-response relationship between aspirin/NSAID use and prostate cancer is an important limitation of this study. Second, we did not have updated data available on aspirin/NSAID use during the study.…”

Section: Discussionsupporting

confidence: 83%

Aspirin, NSAIDs, and Risk of Prostate Cancer: Results from the REDUCE Study

Vidal

Howard

Moreira

et al. 2015

Clinical Cancer Research

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Purpose A recent meta-analysis showed aspirin was associated with reduced prostate cancer (PC) risk. As anti-inflammatory medications lower PSA levels, whether these findings reflect reduced PC detection or lower PC risk is unknown. We tested the association between aspirin and non-aspirin NSAID on PC diagnosis in REDUCE, where all men received biopsies at 2- and 4-years largely independent of PSA. REDUCE tested dutasteride for PC risk reduction in men with a PSA of 2.5-10.0 ng/mL and a negative pre-study biopsy. Experimental Design We examined the association between aspirin, NSAID or both and total, low-grade (Gleason<7), or high-grade (Gleason≥7) PC vs. no PC using multinomial logistic regression among 6,390 men who underwent ≥1 on-study biopsy. Multivariable analyses were adjusted for age, race, geographic region, PSA, prostate volume, digital rectal examination, BMI, treatment arm, smoking, alcohol, statins, hypertension, diabetes and cardiovascular disease. Results Overall, 3,169 men (50%) were non-users, 1,368 (21%) used aspirin, 1,176 (18%) used NSAID, and 677 (11%) used both. In unadjusted models, aspirin was associated with reduced PC risk (OR=0.85, p=0.036). In multivariable analyses, aspirin was associated with reduced total PC risk (OR=0.81, p=0.015). Use of NSAID or NSAIDs and aspirin was not associated with total, low- or high-grade PC, though all ORs were <1 (all p≥0.08). Therefore, we created a dichotomous variable of aspirin and/or NSAID user vs. not. On multivariable analysis, the use of aspirin and/or NSAID was significantly associated with decreased total (OR=0.87, p=0.030) and high-grade (OR=0.80, p=0.040), but not with low-grade PC risk (OR=0.90, p=0.15). Results were similar in placebo and dutasteride arms. Conclusions Among men with a negative biopsy, aspirin and/or NSAID use was associated with decreased PC risk. Additional studies are warranted.

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Section: Discussionsupporting

confidence: 83%

Aspirin, NSAIDs, and Risk of Prostate Cancer: Results from the REDUCE Study

Vidal

Howard

Moreira

et al. 2015

Clinical Cancer Research

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“…Some studies have found evidence of a decreased risk of PCa for men taking aspirin, 5,6,7,8,9 whereas other studies have not found any association. 32,33 The results of our study may help explain some of these conflicting results. If aspirin reduces risk of T2E positive PCa, but not T2E negative PCa, the results of the previous studies may vary based on the T2E gene fusion status of the patients included.…”

Section: Discussionmentioning

confidence: 83%

Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status

Wright

Chéry

Holt

et al. 2015

Prostate Cancer Prostatic Dis

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Background The TMPRSS2:ERG (T2E) gene fusion is the most common rearrangement in prostate cancer (PCa). It is unknown if these molecular subtypes have a different etiology. We evaluated aspirin and non-aspirin NSAIDs in association with T2E fusion status. Methods Subjects were from a population-based case-control study of PCa. T2E fusion status for prostatectomy cases (n=346) was determined by FISH. Medication use was determined from questionnaires. Logistic regression, controlling for age, race, PCa family history, and PSA screening, was used to evaluate the association of T2E fusion status according to medication use. Results T2E fusion was present in 171 (49%) cases, with younger cases more likely to be fusion positive (p<0.01). Current aspirin use was associated with a 37% risk reduction of T2E positive tumors (adjusted OR 0.63, 95% CI 0.43–0.93). Aspirin use was not associated with T2E negative PCa (adjusted OR 0.99, 0.69–1.42). There were no associations between PCa fusion status and use of non-aspirin NSAIDs or acetaminophen. Conclusion Aspirin is associated with a significant reduction in the relative risk of T2E fusion positive, but not T2E negative, PCa. Since inflammation and androgen pathways are implicated in prostate carcinogenesis, additional studies of anti-inflammatory medications in relation to these PCa subtypes are warranted.

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“…Thirty-one studies (18 case–control [9-11,16,17,21-23,26,28-33,35-37] and 13 cohort [7,8,12-15,18-20,24,25,27,34]) addressed the use of any NSAID and its association with PCa incidence risk (Table 1); eight studies (two case–control [41,44] and six cohort [39,40,42,43,45,46]) investigated whether NSAID use was associated with PCa-specific mortality (Table 2). For NSAID use and PCa incidence risk, the publication dates of the studies ranged between 1989 and 2014.…”

Section: Resultsmentioning

confidence: 99%

Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis

Liu

Chen

Xie

et al. 2014

BMC Med

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BackgroundIt has been postulated that non-steroidal anti-inflammatory drugs (NSAIDs) use leads to decreased prostate cancer (PCa) risk. In recent years, NSAIDs’ role in PCa development has been extensively studied; however, there is not yet a definitive answer. Moreover, the epidemiological results for NSAIDs’ effect on PCa-specific mortality have been inconsistent. Therefore, we performed a meta-analysis to examine the controversy.MethodsWe performed a literature database search and included all published studies conducted in the general population exposed to any NSAID, extracting an odds ratio (OR) or a hazard ratio (HR) with 95% confidence intervals (95% CIs) that compared the incidence of PCa or PCa-specific mortality with non-exposure. We derived a pooled OR or HR using random or fixed effects models, as appropriate. Subgroup analyses were also performed.ResultsThirty-nine studies (20 case–control and 19 cohort studies) were included in this analysis. Thirty-one studies were available concerning NSAID use and PCa incidence and eight studies on PCa-specific mortality. Compared to non-use, aspirin use was statistically significantly associated with PCa incidence risk, and the association was slightly stronger for advanced PCa than for total PCa (OR = 0.92, 95% CI = 0.87 to 0.97 for total PCa; OR = 0.81, 95% CI = 0.73 to 0.89 for advanced PCa). Aspirin use seems also to be associated with a modest reduction in PCa-specific mortality (HR = 0.86, 95% CI = 0.78 to 0.96 for total PCa; OR = 0.81, 95% CI = 0.71 to 0.92 for advanced PCa). Generally, the pooled effects for any NSAIDs, NA-NSAIDs and cyclooxygenase-2 inhibitors demonstrated no adverse or beneficial effects on PCa development or PCa-specific mortality, but the results were not consistent. The effect estimates did not vary markedly when stratified by study design and study quality but varied by geographic region. Furthermore, long-term aspirin use (≥4 years) was also significantly associated with reduced PCa incidence (OR = 0.88, 95% CI 0.79 to 0.99).ConclusionsThe present meta-analysis provides support for the hypothesis that aspirin use is inversely related to PCa incidence and PCa-specific mortality. The effect estimates, varying by geographic region, deserve further investigation.

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Use of Non-Steroidal Anti-Inflammatory Drugs and Prostate Cancer Risk: A Population-Based Nested Case-Control Study

Cited by 51 publications

References 40 publications

Aspirin, NSAIDs, and Risk of Prostate Cancer: Results from the REDUCE Study

Aspirin, NSAIDs, and Risk of Prostate Cancer: Results from the REDUCE Study

Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status

Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis

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