Veitonmäki T, Tammela TL, Auvinen A, Murtola TUse of aspirin, but not other non-steroidal anti-inflammatory drugs is associated with decreased prostate cancer risk at the population level. Eur J Cancer 49(4): 938-945
ABSTRACT The cyclooxygenase 2 (COX-2) enzyme overexpression in prostate cancer has led to the hypothesis that COX-2 inhibition may reduce prostate cancer growth. Some previous studies have linked the usage of COX-2 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) with a decreased prostate cancer risk. We estimated the association between cumulative COX-2 inhibition by NSAID usage and prostate cancer risk at population level. All new prostate cancer cases in Finland during 1995-2002 and matched controls (24,657 case-control pairs) were identified from national registries. Detailed information on medication purchases was obtained from a national prescription database. A total cumulative COX-2 inhibition value was calculated based on total cumulative mg amount of each NSAID drug and the drug-specific COX-1/COX-2 inhibition ratio. Prostate cancer risk was analysed with propensity score-matched conditional logistic regression model. In total, 53.8% of the cases and 46.5% of the controls had any prescription-use of NSAIDs, while 8.1% and 7.9%, respectively, had used aspirin. Compared to the non-users, any NSAID use was associated with an elevated overall prostate cancer risk (46.4% versus 53.6%, respectively; odds ratio [OR] 1.3, 95% confidence interval [CI] 1.3, 1.4) and risk of advanced cancer (11.8% versus 14.1%; OR 1.6, 95% CI 1.5, 1.8). The risk remained elevated despite the amount of cumulative COX-2 inhibition. In a separate analysis, the risk increase was similar for each NSAID with the exception of aspirin, which was associated with a decreased overall prostate cancer risk (OR 0.90, 95% CI 0.84, 0.96) in a dose-dependent fashion. NSAID use is associated with an increased prostate cancer risk at the population level regardless of the COX-2 inhibition. This may be explained by systematic differences between prescription NSAID users and non-users. In contrast, aspirin use is associated with a decreased overall prostate cancer risk. Further studies on aspirin and prostate cancer will be needed.
- SourceAvailable from: Hitoshi Ishiguro
[Show abstract] [Hide abstract]
- "Inflammation of the prostate is associated with the induction of cytokines, chemokines, and growth factors, as well as COX-2, which is also overexpressed in prostate cancer  . Given their anti-inflammatory roles in the reduction of COX activity and prostaglandin synthesis, therefore  , it has been speculated that treatment with NSAIDs might reduce the risk of prostate cancer . In vitro studies have provided evidence pointing to the suppression of prostate cancer development and progression by NSAIDs. "
ABSTRACT: Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- (COX-) 1 and 2. Activation of COX-1 and COX-2 results in increased levels of prostaglandins and the induction of angiogenic, antiapoptotic and inflammatory processes. Inhibition of COX enzymes by members of the widely used nonsteroidal anti-inflammatory drug (NSAID) class of drugs decreases prostaglandin production, and exerts a variety of anti-inflammatory, antipyretic, and antinociceptive effects. While numerous in vitro, in vivo, and clinical studies have shown that NSAIDs inhibit the risk and progression of prostatic diseases, the relationship between NSAIDs and such diseases remains controversial. Here we review the literature in this area, critically analyzing the benefits and caveats associated with the use of NSAIDs in the treatment of prostatic diseases.BioMed Research International 05/2014; 2014:436123. DOI:10.1155/2014/436123 · 2.71 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The current study was performed to evaluate whether baseline acute and chronic prostate inflammation among men with an initial negative biopsy for prostate cancer (PCa) increased the risk of subsequent PCa detection in a clinical trial with systematic biopsies. A retrospective analysis was performed of 6238 men aged 50 years to 75 years with prostate-specific antigen levels between 2.5 ng/mL and 10 ng/mL and a prior negative biopsy in the REduction by DUtasteride of PCa Events study who completed a 2-year biopsy. PCa, acute prostate inflammation, and chronic prostate inflammation were assessed by central review. The association between inflammation in baseline prostate biopsies and positive 2-year and 4-year repeat biopsies was evaluated with the chi-square test and logistic regression analysis adjusting for baseline covariates. Acute and chronic inflammation and both were detected in 46 baseline biopsies (1%), 3931 baseline biopsies (63%), and 892 baseline biopsies (14%), respectively. Acute and chronic inflammation were found to be significantly associated with each other (P < .001). Acute inflammation at baseline biopsy was associated with younger age, lower prostate-specific antigen levels, and a smaller prostate (all P < .01), whereas chronic inflammation was associated with older age and larger prostate glands (all P < 0.01). At the 2-year biopsy, the prevalence of PCa was 14% (N = 900 patients). On univariable and multivariable analysis, both acute and chronic inflammation were found to be significantly associated with a lower PCa risk (acute univariable: odds ratio [OR], 0.65 [P < .001] and multivariable: OR, 0.75 [P = .012] and chronic univariable: OR, 0.61 [P < .001] and multivariable: OR, 0.65 [P < .001]). At the time of 4-year biopsy, only acute inflammation was found to be associated with a lower PCa risk. Baseline acute and chronic inflammation were both found to be independently associated with a lower PCa risk. From a clinical standpoint, inflammation in negative biopsies for PCa may lower the risk of subsequent PCa detection. Cancer 2013. © 2013 American Cancer Society.Cancer 04/2013; 189(4). DOI:10.1002/cncr.28349 · 4.90 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Accruing evidence suggests that inflammation plays a role in prostate carcinogenesis. However, studies investigating this association using C-reactive protein (CRP) and interleukin-6 as markers of inflammation have reported conflicting results. We investigated the associations of three common markers of inflammation (CRP, fibrinogen and leukocyte count) and the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow-up period of 24 years (21 to 26 years), 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. We investigated the associations between the markers and risk of prostate cancer using Cox proportional hazards model, adjusting for potential confounders. Elevated pre-diagnostic leukocyte count was associated with an increased risk of prostate cancer. In multivariable adjusted model, the relative risk of prostate cancer among men in the highest tertile of leukocyte count compared to men in the lowest tertile was 1.60 (95%CI 1.10-2.29, p-trend=0.01). Circulating CRP and fibrinogen were not associated with increased risk. The corresponding relative risks for elevated CRP and fibrinogen concentrations were1.08 (95%CI 0.74-1.60, p-trend=0.56) and 1.25 (95%CI 0.87-1.81, p-trend=0.14), respectively. Men with elevated leukocyte counts had a 2.57-fold (95%CI 0.99-6.79) increased risk of prostate cancer mortality. The increased risk associated with elevated leukocyte counts warrants confirmation in other studies. Larger studies should consider evaluating risk by combining at least two markers or using an inflammation score derived from many inflammatory markers.International Journal of Cancer 06/2013; 133(12). DOI:10.1002/ijc.28313 · 5.01 Impact Factor