Veitonmaki T, Tammela TL, Auvinen A, Murtola TJUse 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

ArticleinEuropean journal of cancer (Oxford, England: 1990) 49(4) · October 2012with27 Reads
Impact Factor: 5.42 · DOI: 10.1016/j.ejca.2012.09.030 · Source: PubMed
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.

    • "...ostate cancer is decreased in patients treated with acetylsalicylic acid but not with other NSAIDs [18]. In the pathogenesis of cancer, COX-2 appears to be involved in the signaling pathways linked to ce..."
      Literature reports have documented that aspirin, as well as other NSAIDs, inhibits cyclooxygenase, especially COX-2, and is able to protect against the development of several neoplastic diseases [2,151617. Veitonmäki, et al., reported that the risk of prostate cancer is decreased in patients treated with acetylsalicylic acid but not with other NSAIDs [18]. In the pathogenesis of cancer, COX-2 appears to be involved in the signaling pathways linked to cell proliferation, migration, apoptosis, and tumor angiogenesis [15,19,20].
    [Show abstract] [Hide abstract] ABSTRACT: This study aimed to evaluate the behavior of non-muscle-invasive bladder cancer (NMIBC) in patients submitted to transurethral bladder resection (TURB) comparing subjects in chronic therapy with aspirin, statins, or both drugs to untreated ones. This retrospective study was conducted on 574 patients diagnosed with NMIBC who underwent TURB between March 2008 and April 2013. The study population was divided into two main groups: treated (aspirin and/or statins) and untreated. The treated group was further divided into three therapeutic subgroups: Group A (100 mg of aspirin, daily for at least two years); Group B (20 mg or more of statins, daily for at least two years); and Group C (100 mg of aspirin and 20 mg of statins together).The mean follow-up of patients was 45.06 months. No significant differences were observed among the different groups at baseline. On multivariate analysis, statin treatment, smokers and high stage disease (T1) achieved the level of independent risk factor for the occurrence of a recurrence. When patients were stratified according to the different treatment; patients treated with statins (Group B) presented an higher rate of failure (56/91 patients; 61.5%) when compared to Group A (42/98 patients; 42.9%), Group C (56/98; 57.1%) and (133/287 patients; 46.3%). This difference corresponds to a significant difference in recurrence failure free survival (p = 0.01). Our results suggest that long-term treatment with aspirin in patients with NMIBC might play a role on reducing the risk of tumor recurrence. In contrast, in our investigation data from statins and combination treatment groups showed increased recurrence rates. A long-term randomized prospective study could definitively assess the possible role of this widely used drugs in NMIBC.
    Full-text · Article · Dec 2015 · BMC Cancer
    0Comments 2Citations
    • "...icantly elevated prostate cancer risk of total and advanced prostate cancer among all- NSAID users [27]. The association was not dose-dependent in the study, indicating that it could result from systemat..."
      To explain the phenomenon, we took a deeper look at the included studies. One study conducted in Finland illustrated a significantly elevated prostate cancer risk of total and advanced prostate cancer among all- NSAID users [27]. The association was not dose-dependent in the study, indicating that it could result from systematic differences between users of prescription NSAIDs and users of non-prescription NSAIDs.
    [Show abstract] [Hide abstract] ABSTRACT: Background Epidemiological studies of the association between nonsteroidal anti-inflammatory drug (NSAID) intake and the risk of prostate cancer still remain controversial. Therefore, we conducted a meta-analysis to evaluate the potential association between NSAID intake and prostate cancer risk. Methods Eligible studies were retrieved by both computerized searches and reviews of references. Subgroup analyses on country and design of study were also performed. Random or fixed-effect models were used to pool estimates of odds ratios (ORs) with 95% confidence intervals (CIs). Results We observed that the intake of aspirin was associated with a marginally decreased risk of prostate cancer (OR =0.95, 95% CI =0.93 to 0.98). A similar result was found between nonaspirin NSAIDs and prostate cancer risk (OR =0.94, 95% CI =0.90 to 0.98). However, a positive relation between all-NSAID intake and prostate cancer risk was observed (OR =1.18, 95% CI =1.15 to 1.22). Conclusions We observed a marginally inverse correlation between the intake of aspirin and prostate cancer risk. On the contrary, a positive relationship between all-NSAID intake and prostate cancer was detected. Further research needs to be conducted to better clarify potential biological mechanisms.
    Full-text · Article · Oct 2014 · World Journal of Surgical Oncology
    Xiao Wang Xiao Wang Yi-Wei Lin Yi-Wei Lin Jian Wu Jian Wu +7 more authors... Yi Zhu Yi Zhu
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    • "...i-inflammatory roles in the reduction of COX activity and prostaglandin synthesis, therefore [37] [42], it has been speculated that treatment with NSAIDs might reduce the risk of prostate cancer [43]. I..."
      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 [21] [41]. Given their anti-inflammatory roles in the reduction of COX activity and prostaglandin synthesis, therefore [37] [42], it has been speculated that treatment with NSAIDs might reduce the risk of prostate cancer [43]. In vitro studies have provided evidence pointing to the suppression of prostate cancer development and progression by NSAIDs.
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · May 2014 · BioMed Research International
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    • "... trial, resulting in invalid statistical analysis in these groups. In a study by Veitonmaki et al. [37] in 2013, a dose–effect relationship was found, indicating a significant inverse association (OR = 0..."
      Although some studies have provided this information, they varied in each trial, resulting in invalid statistical analysis in these groups. In a study by Veitonmaki et al. [37] in 2013, a dose–effect relationship was found, indicating a significant inverse association (OR = 0.83) only among participants who used aspirin at the dosage of 37 to 1,300 defined daily dose (DDD). The other benefit was shown among those who took more than one aspirin pill per day [23,29,34], a low dose (≤75 mg/ daily) [27,32], larger doses (≥325 mg/daily) [26] or more than six tablets/week [20]; nevertheless, other studies found no evidence of a dose–effect [7,10,17,19,33,35] or frequency–effect [14,16,17] relationship.
    [Show abstract] [Hide abstract] ABSTRACT: It 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. We 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. Thirty-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). The 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.
    Full-text · Article · Mar 2014 · BMC Medicine
    0Comments 21Citations
    • "...licting results. Acetylsalicylic acid has been associated with a decreased risk of prostate cancer [10]. In men with a preexisting diagnosis of prostate cancer, a prospective study did not show an associ..."
      Studies evaluating the effect of statins or ASA on outcomes of men receiving curative intent treatment for prostate cancer have reported conflicting results. Acetylsalicylic acid has been associated with a decreased risk of prostate cancer [10]. In men with a preexisting diagnosis of prostate cancer, a prospective study did not show an association between this medication and prostate cancer death [11]; this is in contrast to a more recent study which found a lower risk of prostate cancer death in users of acetylsalicylic acid [12].
    [Show abstract] [Hide abstract] ABSTRACT: Background. Prior studies evaluating the effect of statins or acetylsalicylic acid (ASA) on the survival of men receiving prostate cancer were treatment have reported conflicting results, and have not adjusted for comorbidity. Our aim is to investigate the influence of statins and ASA on prostate cancer survival, when comorbidity is adjusted for, in men treated with external beam radiation therapy (EBRT) for prostate cancer. Methods. A cohort of 3851 patients with prostate cancer treated with curative EBRT ± androgen deprivation therapy (ADT) between 2000 and 2007. Stage, treatment, medication use, and Charlson comorbidity index (CCI) scores were analyzed. Results. Median followup was 8.4 years. Mean age was 70.3 years. Neoadjuvant ADT was used in 67%. Statins were used in 23%, ASA in 24%, and both in 11%. Comorbidity scores were 0 in 65%, 1 in 25%, and ≥2 in 10% of patients. Statin and ASA use were associated with increased age and comorbidity. Although statin and ASA use were significantly associated with improved prostate cancer specific survival (PCSS) on univariate analysis, neither were on multivariate analysis. Conclusion. Neither statin nor ASA use impacted PCSS on multivariate competing risks analysis. Survival was impacted by increased comorbidity as well as statin and ASA use.
    Full-text · Article · Mar 2014
    0Comments 4Citations
    • "...ated with regular use of aspirin (but not with alternative non-steroidal anti-inflammatory drugs), [45] ], frequent aspirin use within the SAPCS was inversely correlated with prostate cancer. This dispar..."
      Although no association with the presence of STDs was observed, we cannot exclude that increased ejaculation, associated with sexual activity (or inversely associated with erectile dysfunction), may not be driving protection as a result of pathogenic shedding, specifically within an environment where pathogenic diseases are significant health concerns. Compared to a recent report that suggests a decreased risk of prostate cancer associated with regular use of aspirin (but not with alternative non-steroidal anti-inflammatory drugs), [45] ], frequent aspirin use within the SAPCS was inversely correlated with prostate cancer. This disparity may be impacted by the generic employment of the term aspirin, often used to refer to any form of headache medicine, including paracetemol, which exhibits very minor anti-inflammatory activity.
    [Show abstract] [Hide abstract] ABSTRACT: Although African ancestry represents a significant risk factor for prostate cancer, few studies have investigated the significance of prostate cancer and relevance of previously defined genetic and epidemiological prostate cancer risk factors within Africa. We recently established the Southern African Prostate Cancer Study (SAPCS), a resource for epidemiological and genetic analysis of prostate cancer risk and outcomes in Black men from South Africa. Biased towards highly aggressive prostate cancer disease, this is the first reported data analysis. The SAPCS is an ongoing population-based study of Black men with or without prostate cancer. Pilot analysis was performed for the first 837 participants, 522 cases and 315 controls. We investigate 46 pre-defined prostate cancer risk alleles and up to 24 epidemiological measures including demographic, lifestyle and environmental factors, for power to predict disease status and to drive on-going SAPCS recruitment, sampling procedures and research direction. Preliminary results suggest that no previously defined risk alleles significantly predict prostate cancer occurrence within the SAPCS. Furthermore, genetic risk profiles did not enhance the predictive power of prostate specific antigen (PSA) testing. Our study supports several lifestyle/environmental factors contributing to prostate cancer risk including a family history of cancer, diabetes, current sexual activity and erectile dysfunction, balding pattern, frequent aspirin usage and high PSA levels. Despite a clear increased prostate cancer risk associated with an African ancestry, experimental data is lacking within Africa. This pilot study is therefore a significant contribution to the field. While genetic risk factors (largely European-defined) show no evidence for disease prediction in the SAPCS, several epidemiological factors were associated with prostate cancer status. We call for improved study power by building on the SAPCS resource, further validation of associated factors in independent African-based resources, and genome-wide approaches to define African-specific risk alleles.
    Full-text · Article · Dec 2013 · BMC Urology
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