Aspirin, salicylates, and cancer.
ABSTRACT Evidence from a wide range of sources suggests that individuals taking aspirin and related non-steroidal anti-inflammatory drugs have reduced risk of large bowel cancer. Work in animals supports cancer reduction with aspirin, but no long-term randomised clinical trials exist in human beings, and randomisation would be ethically unacceptable because vascular protection would have to be denied to a proportion of the participants. However, opportunistic trials of aspirin, designed to test vascular protection, provide some evidence of a reduction in cancer, but only after at least 10 years. We summarise evidence for the potential benefit of aspirin and natural salicylates in cancer prevention. Possible mechanisms of action and directions for further work are discussed, and implications for clinical practice are considered.
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ABSTRACT: Background:Aspirin has been widely reported to reduce the incidence of colorectal cancer. Recently, a survival benefit after diagnosis has also been suggested. Data regarding such a benefit are to date contradictory. This study examines the effect of non-steroidal anti-inflammatory drug (NSAID) use on mortality in colorectal cancer in a larger patient cohort than previously to further clarify this effect, especially in terms of exposure timing and dosing.Methods:A study using the General Practice Research Database assessed whether aspirin or NSAID exposure in the year immediately following diagnosis affected all-cause mortality in a cohort of 13 994 colorectal cancer patients. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index and comorbidity.Results:Overall mortality was slightly lower in patients treated with aspirin, (hazard ratio (HR)=0.91; 95% confidence interval (CI)=0.82-1.00). This effect was observed only in patients treated with prophylaxis-dose aspirin (HR=0.89, CI=0.80-0.98) and only in patients taking aspirin before diagnosis (HR=0.86, CI=0.76-0.98). Differential effects were observed depending on the time after diagnosis. Up to 5 years, a reduction in mortality was observed for aspirin users (HR=0.83, CI=0.75-0.92), whereas after 10 years there was an increase in mortality (HR=1.94, CI=1.26-2.99). For NSAID use, no significant effect was observed on overall mortality (HR=1.07, CI=0.98-1.15). High-dose NSAID use was associated with a slight increase in mortality (HR=1.41, CI=1.26-1.56).Interpretation:These findings provide further indication that aspirin may be beneficial in reducing mortality in colorectal cancer during the first 5 years. The same cannot be said for other NSAIDs, where a small increase in mortality was observed.British Journal of Cancer 09/2012; 107(9):1602-7. DOI:10.1038/bjc.2012.427 · 4.82 Impact Factor
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ABSTRACT: Barrett's esophagus (BE) is one of the most common premalignant lesions in which normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. Esophageal adenocarcinoma (EA) develops through progression from BE to low- and high-grade dysplasia (LGD/HGD) and to adenocarcinoma. It is widely accepted that inflammation can increase cancer risk, promoting tumor progression. Therefore, inflammation is regarded as the seventh hallmark of cancer. In recent years, the inflammation-cancer connection of Barrett's carcinogenesis has been intensively studied, unraveling genetic abnormalities. Besides genetic alterations, inflammation is also epigenetically linked to loss of protein expression through transcriptional silencing via promoter methylation. Key mediators linking inflammation and Barrett's carcinogenesis include reactive oxygen species (ROS), NFκB, inflammatory cytokines, prostaglandins, and specific microRNAs (miRNAs). Therefore, the decipherment of molecular pathways that contain these and novel inflammatory key mediators is of major importance for diagnosis, therapy, and prognosis. The detailed elucidation of the signaling molecules involved in Barrett's carcinogenesis will be important for the development of pharmaceutical inhibitors. We herein give an overview of the current knowledge of the inflammation-mediated genetic and epigenetic alterations involved in Barrett's carcinogenesis. We highlight the role of oxidative stress and deregulated DNA damage checkpoints besides the NFκB pathway.Pathology - Research and Practice 04/2012; 208(5):269-80. DOI:10.1016/j.prp.2012.03.007 · 1.56 Impact Factor