Anti-inflammatory agents in ageing and age-associated diseases

Ageing and inflammation might be considered as natural partners. Numerous mechanisms of an inflammatory basis for several age-associated diseases have been identified. Some markers of inflammation are already being integrated into clinical medicine. Furthermore, existent anti-inflammatory drugs and novel candidates have been found to specifically target inflammation pathways in the ageing processes. In this review, we focus on the current knowledge on the field, from the molecular and cellular level to the therapeutic potential of anti-inflammatory agents. First, we present several theories of ageing, in order to explore the involvement of inflammation and to define targets of intervention. Then, we discuss the current approaches and applications as well as the future trends in research regarding the involvement of anti-inflammatory agents in the ageing processes. © 2006 Bentham Science Publishers Ltd

Does pravastatin promote cancer in elderly patients? A meta-analysis

Background: An increase in the incidence of cancer among elderly people assigned to pravastatin therapy has been reported in a randomized controlled trial; however, this finding has been attributed to chance. Our aim was to assess the effect of pravastatin therapy on cancer risk and to examine whether the effect varies according to age by performing a detailed meta-analysis and meta-regression analysis of randomized controlled trials. Methods: We performed a comprehensive literature search for relevant studies published before February 2006. Before analysis, the selected studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates with 95% confidence intervals (CIs) were calculated using fixed-and random-effects models. Meta-regression analysis was performed to examine the impact of age on the study estimates of the relative risk of cancer due to pravastatin therapy. Results: Twelve trials that investigated the use of pravastatin therapy for cardiovascular outcomes were included in the analysis (n = 42 902). Although the overall association between pravastatin use and cancer was not statistically significant in the fixed-effects (risk ratio [RR] 1.06, 95% CI 0.99 - 1.13) or random-effects model (RR 1.06, 95% CI 0.97 - 1.14), the meta-regression analysis showed that the age of study participants significantly modified the effect of pravastatin therapy on cancer risk (p = 0.006). Specifically, this analysis showed that pravastatin therapy was associated with an increasing risk of cancer as age increased. This finding was remarkably robust in the sensitivity analysis. Interpretation: Our findings suggest an association between pravastatin therapy and cancer in elderly patients. However, given the importance of this potential association, further verification is warranted. © 2007 Canadian Medical Association or its licensors

Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies

Statins have been suggested to prevent prostate cancer. Our aim was to examine statin use in relation to both total prostate cancer and the more clinically important advanced prostate cancer, through a detailed metaanalysis of the epidemiologic studies published on the subject in peer-reviewed literature. A comprehensive search for articles published up to November 2007 was performed, reviews of each study were conducted and data were abstracted. Prior to metaanalysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup and sensitivity analyses were also performed. Nineteen studies [6 randomized clinical trials (RCTs), 6 cohort and 7 case-control studies] contributed to the analysis. There was no evidence of an association between statin use and total prostate cancer among either RCTs (RR = 1.06, 95% CI: 0.93-1.20) or the observational studies (RR = 0.89, 95% CI: 0.65-1.24). However, high heterogeneity was detected among the observational studies. Moreover, long-term statin use did not significantly affect the risk of total prostate cancer (RR = 0.93, 95% CI: 0.77-1.13). In contrast, synthesis of the available reports that had specifically examined statin use in relation to advanced prostate cancer indicated a protective association (RR = 0.77, 95% CI: 0.64-0.93). Our results do not support the hypothesis that statins reduce the risk of total prostate cancer. However, further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal. © 2008 Wiley-Liss, Inc

Paracetamol use and risk of ovarian cancer: A meta-analysis

Aim: Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Methods: A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Results: Eight studies (four case-control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random-effects model (RR = 0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed-effects model (RR = 0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; 'regular use' was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non-use (RR = 0.70, 95% CI 0.51, 0.95). Conclusions: Our meta-analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol's potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance. © 2005 Blackwell Publishing Ltd

Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: Evidence from a meta-analysis of 12 studies

OBJECTIVES: Recent experimental research on a class of pharmacological agents that reduce plasma cholesterol, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), has shown promise in pancreatic cancer chemoprevention. While the mechanism remains unclear, several epidemiological studies have also evaluated the relationship between statin use and pancreatic cancer. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. METHODS: A comprehensive search for articles published up to December 2007 was performed, reviews of each study were conducted, and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Twelve studies (3 randomized placebo-controlled trials [RCTs], 4 cohort, and 5 case-control studies) contributed to the analysis. The studies were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and pancreatic cancer among either the RCTs (RR 0.99, 95% CI 0.44-2.21) or the observational studies (RR 0.86, 95% CI 0.60-1.24). Similarly, we found no evidence of publication bias. However, a high heterogeneity was detected among the observational studies. CONCLUSION: Despite the chemopreventive potential of statins demonstrated in experimental studies, our results do not support the hypothesis that these agents reduce the risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia. © 2008 by Am. Coll. of Gastroenterology

Do nonsteroidal anti-inflammatory drugs affect the risk of developing ovarian cancer? A meta-analysis

Aim: The relationship between the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, and the risk of ovarian cancer has been controversial. This study examines the strength of this association by conducting a detailed meta-analysis of the studies published in peer-reviewed literature on the subject. Methods: A comprehensive search for articles published up to April 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated. Results: Ten reports (six case-control and four cohort studies), published between 1998 and 2004, were identified. There was no evidence of an association between aspirin use and ovarian cancer risk either assuming a random-effects model (RR = 0.92, 95% CI 0.80, 1.06), or a fixed-effects model (RR = 0.93, 95% CI 0.81, 1.06). Similarly, we did not find evidence of an association between non-aspirin NSAID use and ovarian cancer, both on the basis of a random-effects model (RR = 0.86, 95% CI 0.68, 1.08), and on the basis of a fixed-effects model (RR = 0.88, 95% CI 0.76, 1.01). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, our analysis did not show decreasing risks with increasing frequency or duration of use, features often associated with causal relationships. Conclusions: Our meta-analysis findings do not support that NSAID use plays a role in the chemoprevention of ovarian cancer. Future research should examine potential relationships between specific NSAIDs and ovarian cancer, taking into account the possible biases that may have affected this meta-analysis. © 2005 Blackwell Publishing Ltd

Statin use and breast cancer: Do we need more evidence and what should this be?

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have been proved highly effective treatments for primary and secondary prevention of cardiovascular diseases. Despite widespread and long-term use of statins, there is still a debate concerning their association with cancer at various sites, including breast. As of today, the accumulated epidemiological evidence does not support the hypothesis that statin use affects the risk of developing breast cancer when taken at low doses for managing hypercholesterolemia. However, current evidence cannot exclude an increased risk of breast cancer with statin use in subsets of individuals, for example, the elderly. On the other hand, some studies show that statins might be useful to prevent recurrence and improve survival in patients already suffering from certain breast cancer types. They could also be combined with certain anticancer drugs and potentiate their effects, ameliorate their side effects or prevent the development of resistance. Further research is warranted to clarify these issues. © 2014 Informa UK, Ltd