Research Blog

Daily use of Aspirin Prevents Cancer

aspirin


A new pair of studies suggests that a daily dosage of aspirin for at least five years reduces the risk of cancer.





Aspirin is one of the oldest medicines in human history. In 400 B.C Hippocrates prescribed willow bark containing aspirin. to Greek women to reduce pain during childbirth. In 1897 Bayer's Felix Hoffman develops a method for developing aspirin synthetically.  Although aspirin is normally taken as a painkiller, it has been found to prevent other diseases including cardiovascular disease and, most recently, a variety of cancers. Aspirin acts as a blood thinner, this is the mechanism by which it reduces risk of stroke and heart attack.  

Mounting evidence suggests that taking aspirin on a daily basis reduces cancer risk. A team lead by Professor Peter M. Rothwell out of the University of Oxford has been grabbing headlines with studies providing strong support for aspirin's ability to reduce cancer risk. At the end of 2010 they found by combing through aspirin and heart disease correlational studies that a daily dosage of aspirin reduced long-term risk of developing pancreatic, esophageal, brain, stomach, colorectal and prostate cancers (Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials, 2010, P Rothwell, et al.). The study found that long-term reductions in cancer risk were apparent in subjects who took daily aspirin treatment for at least five years, but the risk-reduction was greater for subjects who took a daily aspirin treatment for more than 7.5 years. In addition, daily aspirin dosages exceeding 85 mg did not appear to reduce relative cancer risk. Additionally, as demonstrated by the figures below, the disparity between the control group and the aspirin dosage experimental group did not appear until 5 to 20 years following the conclusion of the study.


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Effect of allocation to aspirin versus control on the 20-year risk of death due to the most common fatal cancers in the 10,502 patients with scheduled treatment duration of 5 years or longer in the three trials with long-term follow-up.

The analysis also found that subjects over 65 years of age saw a greater absolute reduction in cancer risk. Another interesting finding was that subjects only saw a reduction in cancer risk if they had been on a daily dosage schedule.  Alternate daily dosages did not reduce cancer risk. This suggests that the mechanism by which cancer risk is reduced is not the irreversible inhibition of cox-2 (an enzyme responsible for pain and inflammation that is targeted by aspirin).

Another study, published in 2012 by the same team looked at short-term cancer risk reduction ( Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials, 2012, Peter M Rothwell, et al.). This study found that after a five year delay, cancer mortality was reduced by 40%. Cancer incidence was reduced by 25% after a three year follow-up.  

One of the major drawbacks of taking a daily dosage of aspirin is an increase in risk of extracranial bleeding and hemorrhages. The researchers addressed this in their second study. On the short-term, mortality attributed to vascular disease was not affected and the increase in mortality do to fatal hemorrhaging was more than offset by the reduction in cancer risk. In addition, for non-gastrointestinal cancers, risk reduction was correlated with age.

In summary, these studies show a correlation between reduced cancer risk in all fatal cancers and daily aspirin administration. The reduction in cancer mortality lowers overall mortality, even when factoring aspirin-induced risks such as hemorrhaging.

Retaining Muscle Function in ALS Patients




ALS patients lose significant muscle mitochondrion causing muscle degradation and muscular atrophy. However, as the figure to the right demonstrates, treatment with PGC-1alpha reduces muscle degradation suggesting a therapy for improving quality of life, but not survival, for ALS patients.




Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive, fatal, adult-onset neurodegenerative disorder characterized by loss of motor neurons and degeneration of skeletal muscle.  Approximately 300,000 people are affected by ALS worldwide. Although scientists have not found a cure for the disease, a team of researchers from San Diego, California have found a possible lead for a way to alleviate the muscle degeneration that makes the end of life for ALS patients so painful.  

The study, Elevated PGC-1alpha Activity Sustains Mitochondrial Biogenesis and Muscle Function Without Extending Survival in a Mouse Model of Inherited ALS (Sandrine Da Cruz, Philippe A. Parone, et al., May 2012), looked at the effects of increased transcriptional coactivator PGC-1alpha on SOD1 mutant mice.  PGC-1alpha exerts control over cellular metabolism, specifically mitochondria angiogenesis and biogenesis. The SOD1 mutation causes mitochondrion toxicity that models ALS. The researchers found that by increasing levels of PGC-alpha1, muscle degradation was reduced.  

Mitochondrion density is significantly reduced by ALS, however as the picture above demonstrates, comparing SOD1-mutant mice saw significant increases in skeletal muscle mitochondrion density when treated with PGC-1alpha.Vascular endothelial growth factor (VEGF) levels were also raised by the PGC-1alpha.  The alleviation of muscle degradation resulted in the increased endurance and voluntary physical activity (distance covered in an open field) in the PGC-1alpha treated mice. The results can be seen below.  

Survival Duration

The figure above demonstrates that survival duration was not increased in PGC-1alpha treated/SOD1-mutant mice (blue) compared to SOD1-mutant mice (red).

PPG-1alpha does not alter the pathogenesis of ALS, it simply reduces the effect of mitochondrion toxics that are released in ALS patients.  Unfortunately then, raising PGC-1aplha levels in SOD1-mutant mice did not prevent the motor neurons from being degraded. Thus, PGC-1alpha worked on preventing degradation to the muscular system, but not the terminal nervous system degradation. As the figure below demonstrates, survival duration was not increased by the PGC-1alpha.

This study is significant because it introduces PGC-1alpha as a potential therapy for increasing the quality of life for ALS patients by maintaining muscle function. Unfortunately, PGC-1alpha does not prevent neuron degradation or increase survival duration after onset of ALS. However, it means that Lou Gehrig could have continued playing baseball for a few more months.


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