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: Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. No statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, but tissue PGE2 levels were lower with aspirin compared to placebo (p <0.001). Transcripts differentially expressed between epithelium and stroma (N = 4916, P <0.01, false discovery rate <0.001), included a high proportion of genes involved in cell signaling, cellular movement, and cancer. Genes preferentially expressed in epithelium were involved in drug and xenobiotic metabolism, fatty acid and lipid metabolism, apoptosis signaling, and ion transport. Genes preferentially expressed in stroma included those involved in inflammation, cellular adhesion, and extracellular matrix production. Wnt-Tcf4 pathway genes were expressed in both epithelium and stroma but differed by subcellular location. These results suggest that, in healthy individuals, subtle effects of aspirin on gene expression in normal colon tissue are likely overwhelmed by inter-individual variability in microarray analyses. Differential expression of critical genes between colonic epithelium and stroma suggest that these tissue types need to be considered separately.BMC Medical Genetics 03/2015; 16(1):18. DOI:10.1186/s12881-015-0161-6 · 2.45 Impact Factor
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ABSTRACT: Over the past few decades, the rate of cancer diagnosis has increased worldwide due to the increase in population and average life expectancy, and also, due to the advances in diagnostic medical technology that facilitate early cancer detection and recognition. Nonetheless, the treatment options have not been developed proportional to this increase, with a huge number of patients frequently being diagnosed with different types of fatal cancer. This has prompted different health organizations to search for novel strategies to prevent cancer, or even halt its progression. Having failed to provide optimum vascular protection benefits, especially with the introduction of relatively superior antiplatelets, such as adenosine diphosphate (ADP) receptor inhibitors; clopidogrel and ticagrelor, regular aspirin use was proposed to reduce the risk of common cancers like colorectal cancer, gastric cancer, breast cancer, lung cancer, prostate cancer and haematological malignancies, as suggested by epidemiological studies. However, it is difficult to draw any firm conclusions on such weak data, as this could raise false hopes among patients and physicians and could potentially mislead scientific research. Clearly, current evidence highlights a gap in medical research and emphasizes the need to carry out interventional studies in high risk for cancer patients using specific aspirin doses in order to validate the data. This should also shed some light on the risk-benefit profile in view of the potential for bleeding complications, especially with the higher doses.
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ABSTRACT: Aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease tumor progression in pre-clinical models of ovarian cancer, however the influence of these drugs on survival in women following a diagnosis of ovarian cancer is unknown. We included 1305 Australian women diagnosed with incident invasive epithelial ovarian cancer, recruited into a population-based case-control study. Use of aspirin, nonaspirin NSAIDs and acetaminophen in the 5 years preceding ovarian cancer diagnosis was assessed from self-reports. Deaths were ascertained up to October 2011 via linkage with the Australian National Death Index. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During a mean follow-up time of 4.9 years (SD 2.8 years), there were 834 deaths, of which 779 (93% of deaths) were from ovarian cancer. We found uniformly inverse, but non-significant, HRs for ever use in the last five years of aspirin, nonaspirin NSAIDs and acetaminophen compared with no use (adjusted HRs 0.92 [95% CI 0.81-1.06], 0.91 [95% CI 0.80-1.05] and 0.91 [95% CI 0.69-1.20], respectively). There was no evidence of any dose response trends. The results remained unchanged when we limited the outcome to ovarian cancer mortality. Associations did not differ by histologic subtype, age at diagnosis or stage. Given current interest in the role of aspirin and nonaspirin NSAIDs in cancer survival these results are noteworthy given they are the first to investigate these associations in women with ovarian cancer. Our results provide no strong evidence that pre-diagnostic use of aspirin or nonaspirin NSAIDs are associated with improved survival in women with ovarian cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.Cancer Epidemiology 02/2015; 39(2). DOI:10.1016/j.canep.2014.12.010 · 2.56 Impact Factor