Are we ready to recommend aspirin for cancer prevention?
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ABSTRACT:
SUBMITTER: Chan AT
PROVIDER: S-EPMC3415297 | biostudies-literature | 2012 Apr
REPOSITORIES: biostudies-literature
Publications
Are we ready to recommend aspirin for cancer prevention?
Chan Andrew T AT Cook Nancy R NR
Lancet (London, England) 20120321 9826
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Project description:Over 600,000 people worldwide die of colorectal cancer (CRC) annually, highlighting the importance of developing effective prevention strategies. Among proposed chemopreventive interventions, aspirin is perhaps the agent with the strongest body of evidence that supports wider spread use to significantly reduce the population burden of CRC. Several epidemiological studies, four randomized controlled trials (RCTs) of colorectal polyp recurrence, and RCTs in patients with hereditary colorectal cancer syndromes, have shown that aspirin reduces incidence of colorectal neoplasia. Recently, in a pooled analysis of five cardiovascular-prevention RCTs linked to cancer outcomes, daily aspirin use at any dose reduced the risk of CRC by 24% and of CRC-associated mortality by 35% after a delay of 8-10 years. In an expanded meta-analysis of 8 cardiovascular-prevention RCTs, daily aspirin use at any dose was associated with a 21% lower risk of all cancer death, including CRC, with benefit only apparent after 5 years. In this review, we will summarize human studies of aspirin in CRC prevention as well as discuss the safety profile and mechanism of aspirin in CRC prevention.
| S-EPMC3354696 | biostudies-literature
Project description:There is now a considerable body of data supporting the hypothesis that aspirin could be effective in the prevention and treatment of colorectal cancer, and a number of phase III randomised controlled trials designed to evaluate the role of aspirin in the treatment of colorectal cancer are ongoing. Although generally well tolerated, aspirin can have adverse effects, including dyspepsia and, infrequently, bleeding. To ensure a favourable balance of benefits and risks from aspirin, a more personalised assessment of the advantages and disadvantages is required. Emerging data suggest that tumour PIK3CA mutation status, expression of cyclo-oxygenase-2 and human leukocyte antigen class I, along with certain germline polymorphisms, might all help to identify individuals who stand to gain most. We review both the underpinning evidence and current data, on clinical, molecular and genetic biomarkers for aspirin use in the prevention and treatment of colorectal cancer, and discuss the opportunities for further biomarker research provided by ongoing trials.
| S-EPMC4786609 | biostudies-literature
Project description:Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer prevention and treatment. Preclinical studies support various antitumor effects of vitamin D in breast cancer. Numerous observational studies have reported an inverse association between vitamin D status, including circulating 25-hydroxyvitamin D (25(OH)D) levels, and breast cancer risk. The relationship between vitamin D and mammographic density, a strong predictor of breast cancer risk, remains unclear. Studies analyzing the link between genetic polymorphisms in vitamin D pathway genes and breast cancer incidence and prognosis have yielded inconsistent results. Vitamin D deficiency among breast cancer patients has been associated with poorer clinical outcomes and increased mortality. Despite a number of clinical trials of vitamin D supplementation, the efficacy, optimal dosage of vitamin D, and target blood level of 25(OH)D for breast cancer prevention have yet to be determined. Even with substantial literature on vitamin D and breast cancer, future studies need to focus on gaining a better understanding of the biologic effects of vitamin D in breast tissue. Despite compelling data from experimental and observational studies, there is still insufficient data from clinical trials to make recommendations for vitamin D supplementation for breast cancer prevention or treatment.
| S-EPMC3600307 | biostudies-literature
Project description:PurposePrimary prevention of hormonally insensitive breast cancers remains an important clinical need and repurposing existing low-toxicity drugs represents a low-cost, efficient strategy for meeting this goal. This study targeted the cholesterol pathway using fluvastatin, a cholesterol-lowering drug, and aspirin, an AMPK activator that acts as a brake in the cholesterol pathway, in a transgenic mouse model of triple-negative breast cancer (TNBC).MethodsUsing SV40C3 TAg mice, the efficacy and mechanism of fluvastatin, aspirin, or both in combination were compared with vehicle alone.ResultsSixteen-weeks of fluvastatin treatment resulted in significant delay in onset of tumors (20 weeks vs. 16.8 weeks in vehicle treatment, p = 0.01) and inhibited tumor incidence and tumor multiplicity by 50% relative to the vehicle control. In animals that developed tumors, fluvastatin treatment inhibited tumor weight by 75% relative to vehicle control. Aspirin alone did not significantly affect tumor latency, tumor incidence or tumor burden compared to vehicle control. Fluvastatin and aspirin in combination delayed the onset of tumors but failed to inhibit tumor incidence and tumor multiplicity. The growth-inhibitory effects of fluvastatin were mediated through increased FAS/FASL mediated apoptotic cell death that was characterized by increased cleaved PARP and driven in part by depletion of an isoprenoid, geranyl geranyl pyrophosphate (GGPP).ConclusionsIn line with NCI's emphasis to repurpose low-toxicity drugs for prevention of cancer, fluvastatin was effective for prevention of TNBC and warrants further clinical testing. Aspirin did not provide chemopreventive benefit.
| S-EPMC8190001 | biostudies-literature
Project description:Cancer is the leading cause of death among men and women aged 60-79 years. Colorectal cancer is the third most common cancer in males and the second most common in females, with about 0.8 million deaths worldwide per year. Individuals older than 50 years account for 20-50% of colonic adenomas. Several measures have been proposed to decrease colorectal cancer risks, such as an increase in dietary fiber, use of aspirin, and physical activity. Nonsteroidal anti-inflammatory drugs have been proposed as protective agents against the development of colorectal cancer and colorectal adenomas. Aspirin was the first pharmacological agent endorsed by the United States Preventive Services Task Force screening for colorectal cancer chemoprevention. Although studies have shown up to 40% colorectal cancer risk reduction in individuals at average risk, data regarding this benefit are inconsistent. Several recent studies show that prophylactic use of aspirin in elderly subjects may not be beneficial in preventing the occurrence of colorectal cancers. Given the risks associated with aspirin, such as non-fatal and fatal bleeding events, aspirin's role should be redefined, especially in individuals at risk of bleeding. This review provides a discussion of the recent studies on the role of aspirin use in elderly individuals at risk of colorectal cancer.
| S-EPMC7774657 | biostudies-literature
Project description:Background and purposeAntiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.MethodsRandomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the χ2 test was significant (P value < 0.10) or the I2 > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.ResultsWe included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59-0.82, P <0.05; RR = 0.84, 95% CI: 0.72-0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03-2.23, P = 0.04; RR = 1.54, 95% CI: 1.32-1.79, P<0.05, respectively).ConclusionsDual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.
| S-EPMC4536208 | biostudies-literature
Project description:Although compelling evidence exists on the ability of aspirin to treat colorectal cancer (CRC), and numerous theories and targets have been proposed, a consensus has not been reached regarding its mechanism of action. In this regard, a relatively unexplored area is the role played by aspirin metabolites 2,3‑dihydroxybenzoic acid (2,3‑DHBA) and 2,5‑dihydroxybenzoic acid (2,5‑DHBA) in its chemopreventive actions. In a previous study, we demonstrated that 2,3‑DHBA and 2,5‑DHBA inhibited CDK1 enzyme activity in vitro. The aim of the present study was to understand the effect of these metabolites on the enzyme activity of all CDKs involved in cell cycle regulation (CDKs 1, 2, 4 and 6) as well as their effect on clonal formation in three different cancer cell lines. Additionally, in silico studies were performed to determine the potential sites of interactions of 2,3‑DHBA and 2,5‑DHBA with CDKs. We demonstrated that 2,3‑DHBA and 2,5‑DHBA inhibits CDK‑1 enzyme activity beginning at 500 µM, while CDK2 and CDK4 activity was inhibited only at higher concentrations (>750 µM). 2,3‑DHBA inhibited CDK6 enzyme activity from 250 µM, while 2,5‑DHBA inhibited its activity >750 µM. Colony formation assays showed that 2,5‑DHBA was highly effective in inhibiting clonal formation in HCT‑116 and HT‑29 CRC cell lines (250‑500 µM), and in the MDA‑MB‑231 breast cancer cell line (~100 µM). In contrast 2,3‑DHBA was effective only in MDA‑MB‑231 cells (~500 µM). Both aspirin and salicylic acid failed to inhibit all four CDKs and colony formation. Based on the present results, it is suggested that 2,3‑DHBA and 2,5‑DHBA may contribute to the chemopreventive properties of aspirin, possibly through the inhibition of CDKs. The present data and the proposed mechanisms should open new areas for future investigations.
| S-EPMC6896348 | biostudies-literature
Project description:Aspirin and Inflammation: Mutations, Genes, Pathways and Prevention
| PRJNA507059 | ENA
Project description:Aspirin and Inflammation: Mutations, Genes, Pathways and Prevention
| PRJNA507060 | ENA
Project description:BackgroundInherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals.MethodsA decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER).ResultsThe mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin.ConclusionsGenotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals.ImpactA genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.
| S-EPMC8172453 | biostudies-literature