Link between aspirin and eye condition unclear

reposted from:  http://www.nhs.uk/news/2011/10October/Pages/daily-aspirin-use-amd-vision-loss.aspx

crabsallover highlights, key points, comments / links.

“People who take a daily dose of aspirin are twice as likely to suffer blindness in later life,” The Daily Telegraph reported. The newspaper said that an international study of over 4,000 elderly people found that daily aspirin users are twice as likely to be diagnosed with a late-stage form of age-related macular degeneration(AMD), a common cause of vision problems in older people.

The study examined the association between aspirin use among older people and AMD. To examine the relationship, researchers tested the eyes of 4,691 adults aged over 65. They also assessed their aspirin use and other medical and lifestyle factors. The researchers found that people who took aspirin daily were more than twice as likely to have a more severe, later stage of AMD. This is known as “wet” AMD, and about 15% of people with AMD develop it. However, the relationship between aspirin use and other stages of AMD was not consistent, with aspirin users being no more likely to have mid-stage AMD.

As this study assessed AMD and aspirin use at the same time, it cannot show that regular aspirin use causes or increases the risk of vision problems. As such, we cannot tell whether aspirin use or vision problems came first. On the evidence provided by this particular study, it is not possible to tell how or whether the two are related, or if some unaccounted for factor is linked to both aspirin use and AMD. For example, aspirin is often prescribed to people with cardiovascular problems, which are themselves associated with smoking and obesity. Both of these are risk factors for AMD.

However, the study does raise questions about whether there could be an association between AMD and regular aspirin use, and the subject warrants further investigation.

Where did the story come from?

The study was carried out by researchers from a number of European centres, including Queen’s University, Belfast, and the London School of Hygiene and Tropical Medicine. It was funded by several organisations including the EU and the Macular Disease Society UK. The study was published in Ophthalmology,the peer-reviewed journal of the American Academy of Ophthalmology.

While headlines tended to overstate the certainty of the study’s findings, both the Daily Mail and the Telegraph pointed out that the study provided no evidence that aspirin use itself caused the participants’ AMD. The newspapers also explained that the relationship may be due to confounding factors. For example, it is possible that AMD was caused by cardiovascular disease, which might typically be treated using aspirin.

Some reports suggested that aspirin use was associated with “blindness”, but this may not reflect the nature of AMD. For example, the degree of visual impairment experienced by people with AMD can vary, and people may have distorted vision rather than no vision at all. Although it can cause severe visual impairment as central vision is lost (affecting everyday activities such as reading and writing), it does not usually affect peripheral vision and generally does not cause profound blindness.

What kind of research was this?

This cross-sectional study of nearly 4,700 older people explored the possible association between use of aspirin and the development of age-related macular degeneration (AMD). This type of study can provide a “snapshot” of health-related issues in a particular population at a certain point in time, but it cannot show cause and effect.

AMD (referred to in the research paper as aging macular disorder) is the most common cause of vision loss in people over 50. It occurs when problems affect the workings of the macula, the spot on the back of the eye that is responsible for central vision. This leads to a gradual loss of central vision, which is needed for detailed work and for tasks like driving or reading. However, it does not normally lead to complete blindness.

There are two main types of AMD, called wet and dry AMD. Dry AMD is the most common form. It usually progresses in stages causing gradual loss of vision over time. About 15% of people with AMD develop wet AMD. It is called wet because it is associated with the growth of abnormal new blood vessels in the retina, which are fragile and prone to bleeding.

The researchers say that while previous research has explored an association between aspirin use and AMD, findings have so far been inconsistent.

What did the research involve?

Between 2000 and 2003, researchers recruited participants aged 65 or over by randomly sampling people from national population registers of seven European countries. Participants were interviewed and given a structured questionnaire. This asked about their aspirin intake and other factors such as socioeconomic background, medical history, smoking and alcohol consumption. Aspirin intake was split into four categories ranging from “never” to “daily use”. Researchers also took into account other health measures, such a body mass index, blood pressure and cholesterol levels.

Participants underwent standard ophthalmic tests for AMD, with their AMD progression graded using a five-stage scale. A score of 0 indicated no AMD and the last stage – stage 4 – was also classified as being either dry or wet (not everyone with late-stage AMD will progress to the wet form). The classification system they used is a recognised international grading system.

The researchers then used standard statistical methods to analyse any association between aspirin use and AMD.

What were the basic results?

Of the initial 4,753 participants, the researchers excluded 62 for whom information on aspirin use was missing. This left 4,691 participants. They found that 36.4% (1,706) had early AMD (stages 0–3) and 3.3% (157) had late AMD (stage 4). Of those with stage 4 AMD, 108 had the wet form and 49 the dry form.

Within the whole study population, 41.2% took aspirin once a month, 7% at least once a week and 17.3% took aspirin daily.

After the researchers had adjusted for potential confounders, they calculated the associations between daily aspirin use and each grade of AMD. They found that there was:

• a 26% increased risk of grade 1 AMD (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.08–1.46)
• a 42% increased risk of grade 2 AMD (OR 1.42, 95% CI 1.18–1.70)
• no increased risk of grade 3 AMD
• a more than double risk of grade 4 wet AMD (OR 2.22, 95% CI 1.61–3.05)
• no increased risk of grade 4 dry AMD

How did the researchers interpret the results?

The researchers say that frequent aspirin use was associated with early AMD and wet late AMD. The risk rose with increasing frequency of aspirin use. They consider that, as aspirin acts on the body in several ways, it is possible that it affects blood vessels in the eye. However, further study of this is needed.

Conclusion

This large study had strengths, including the fact that it took a random sample of the population and established the presence of AMD using validated methods and accepted grading procedures for AMD. The researchers also tried to take account of other factors that could have affected the risk of AMD, in particular cardiovascular disease, smoking and excess weight, which are known risk factors for AMD.

The study’s major limitation is its cross-sectional design, which means it cannot establish cause and effect. As such, while the study has shown associations between aspirin use and vision problems, it cannot tell how or whether the two are directly related, nor which came first. While we could speculate that aspirin somehow causes AMD, it could also be suggested that AMD might be the result of cardiovascular conditions that require treatment with aspirin. Also, although the researchers attempted to adjust their analyses for confounders – including those known to be associated with AMD – other factors may be independently related to both aspirin use and AMD and could account for the observed relationship.

The relationship was also not completely consistent. Aspirin use was not associated with grade 3 AMD or grade 4 dry AMD. This suggests that the findings could possibly have happened by chance.

The limitations of the study’s design, together with the inconsistent results of other studies on the matter, mean it is hard to tell if there truly is an association between regular aspirin use and AMD. However, the possibility of an association seems worthy of further exploration. Ideally, this would involve examining people’s eyes to check they do not have AMD and following them over time to see whether people taking aspirin daily are more likely to develop the condition in the future.

Links to the headlines

Regular aspirin users at higher risk of sight problems, research suggests. The Daily Telegraph, October 4 2011

Over-65s who take a daily aspirin are 'twice as likely to suffer age-related sight loss'. Daily Mail, October 4 2011

Links to the science

de Jong PTVM, Chakravarthy U, Rahu M. Associations between Aspirin Use and Aging Macula Disorder. Ophthalmology, September 14 2011 (published online)

Reactive oxygen species (ROS) damage internal cell structure

reposted from: http://www.nhs.uk/news/2011/11November/Pages/common-drug-may-slow-progeria.aspx

crabsallover highlights, key points, comments / links.

NHS.uk say:-

New pill to halt ageing, papers claim

NHS Choices Wed Nov 2, 2011 15:52 Share

Scientists may have “found a cure for ageing”, the Daily Mirror reported. According to the newspaper, the answer could lie in a “forever young” drug that will allow us to grow old gracefully.

However, this seeminly marvelous news is based on a small study which looked at an extremely rare form of a genetic condition called progeria. This causes children’s bodies to rapidly age and leads to a number of physical health problems, limiting their lifespan to an average of around 13 years.

The researchers examined the cells of people with the condition and found that, compared to cells from healthy individuals, they produced five times the level of ‘reactive oxygen species’ (ROS), chemicals that are damaging to the internal cell structure. These higher ROS levels were associated with more breaks in the cells’ DNA and abnormal cell growth. However, when the cells were treated with a drug called N-acetylcysteine, which is already used to prevent liver damage in people who have overdosed on paracetamol, the researchers were able to largely prevent this DNA damage and improve cell growth and division.

The findings of this study are at a very early stage and suggest some potential ways to help people with rare but devastating forms of progeria. However, it is too great a leap too suggest that the research provides a “cure for ageing”, as some fanciful reports have done.

Where did the story come from?

The study was carried out by researchers from Durham University and the University of Bologna in Italy. It was funded by the European Commission and published in the peer-reviewed scientific journal Human Molecular Genetics.

Most news coverage on the research suggested that it could offer a way to slow or even stop routine human ageing. However, the media’s outlandish claims that scientists are on the verge of a “forever young drug” or a “cure for ageing” are not supported by this research.

Several newspapers focussed on the fact that the study used an existing drug called N-acetylcysteine, and implied that it could soon be used to block the effects of ageing. The drug is currently an ingredient in some eye drops and also has a role in treating paracetamol overdoses and poisoning, for which it is given intravenously for short periods. While it has been proven safe and effective for these uses, there are no guarantees that it would be safe or effective if taken orally in the long term.

Only the BBC’s coverage primarily focussed on progeria, the rare rapid-ageing condition that the research examined.

What kind of research was this?

This study was a laboratory-based investigation into the cause of and possible solutions to the genetic damage that occurs in a group of inherited degenerative disorders called laminopathies. These conditions are caused by mutations in a gene called LMNA, which normally produces a protein called lamin A. The lamin A protein plays an important role in keeping the structures within cells strong and stable.

The study focused on the most severe group of laminopathies, including the rare Hutchinson Gilford progeria syndrome (HGPS), which causes children’s bodies to age too quickly. This causes a range of effects, including restricting growth and loss of body fat and hair. Children with HGPS develop heart disease early in life, and have an average life expectancy of just 13 years.

Laboratory studies are the best way to determine exactly what happens in the individual cells of people with these types of genetic conditions. The results can help researchers explain the symptoms that people develop.

...

Previous studies have shown that skin cells from these patients have high levels of chemicals called reactive oxygen species (ROS). ROS can cause double strand breaks in DNA, and are thought to be involved in the accumulation of this type of DNA damage in normal ageing cells. Therefore, the researchers wanted to test whether ROS might be responsible for the DNA damage seen in cells from patients with laminopathies.

The researchers first compared the level of ROS produced by the cells, and then compared the level of damage caused by ROS in the cells. Specifically, they looked at how ROS caused DNA damage and disruption in the shape of the cells’ internal structures.

Finally, they investigated whether a drug called N-acetylcysteine could reduce the damaging effect of the ROS in the healthy and diseased cells. N-acetylcysteine is a chemical that “mops up” the damaging ROS and is already used to prevent liver damage in patients who have overdosed on paracetamol.

What were the basic results?

The researchers found that:

• The cells from people with HGPS had ROS levels that were five times higher than those from healthy individuals.
• The high ROS levels were linked to DNA damage (due to double strand breaks in the DNA).
• The accumulation of DNA damage in these fibroblasts appeared to cause poor cell growth.
• ROS-induced DNA damage could be repaired efficiently in cells from healthy individuals, but could not be repaired in the cells from people with HGPS.
• Adding N-acetylcysteine to the cells of HGPS patients led to a significant increase their ability to grow and multiply. The cells also did not develop un-repairable ROS-induced DNA damage.

How did the researchers interpret the results?

The researchers say their findings suggest that the accumulation of ROS-induced DNA damage can “contribute significantly” to the problems seen in the cells of people with HGPS. They also state that N-acetylcysteine in combination with other treatments “might prove beneficial to HGPS patients”.

Conclusion

This laboratory-based study of isolated human cells provides interesting new evidence on how reactive oxygen species (ROS) potentially causes DNA damage in the accelerated ageing condition Hutchinson Gilford progeria syndrome (HGPS). It also highlights that N-acetylcysteine might be of use in treating patients with HGPS.

While this study provides interesting new findings, the following limitations should be considered:

• This study experimented on isolated human cells in a laboratory, and it is not known what the effect of N-acetylcysteine would be if it was given to children with the illness.
• This is early-stage research, the results of which will need to be confirmed in future studies. The effectiveness and safety of N-acetylcysteine is likely to need to be tested in animal models of the condition before it could be tested in people. However, the fact that N–acetylcysteine is already used as a treatment for paracetamol overdose may mean that human trials could be carried out sooner than for a completely new drug. That said, it would still need to be tested, particular its effects when taken in the long term.
• A full randomised clinical trial of N-acetylcysteine may be difficult to conduct as the condition is so rare. The Progeria Research Foundation says that just 78 children are known to have the condition.
• The newspapers suggest that the findings are applicable to normal ageing, and that N-acetylcysteine could be a “cure for ageing”. This study focussed on the effect of N-acetylcysteine on the cells of patients with HGPS, a rare, severe genetic condition. It is not possible to say from this study how the findings would apply to the normal ageing process.
• HGPS is a genetic condition, and although N-acetylcysteine might be able to reduce or block some of the damage seen in the cells of people with HGPS, it will not remove the genetic mutation itself or allow the body to produce the important lamin A protein.
• Regular cellular and physical ageing involves a complex mix of mechanisms. Even if N-acetylcysteine can block some of them, this does not mean that it could stop or greatly slow the overall ageing process.

These findings are at a very early stage and will aid further research into HGPS. However, it may take many years to confirm these findings through other studies and to assess the effects of N-acetylcysteine in HGPS patients. The implications of these findings for the ageing process of people without HGPS is unclear, and it is certainly too early to say that an “ageing pill” is just around the corner.

Links To The Headlines

Progeria may be treated by drug, researchers say. BBC News, November 2 2011

Breakthrough could lead to treatment for symptoms of growing old. The Daily Telegraph, November 2 2011

Scientists "find cure for ageing". Daily Mail, November 2 2011

Pill 'to combat ageing'. The Sun, November 2 2011

'Forever young' drug that lets you grow old gracefully could soon be reality. Daily Mail, November 2 2011

Links To Science

Richards SA, Muter J, Ritchie P et al. The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Human Molecular Genetics, 2011 20 (20): 3997-4004

Avoid alcohol 3 days a week

reposted from: http://www.nhs.uk/news/2011/10October/Pages/alcohol-advice-royal-college-physicians.aspx

crabsallover highlights, key points, comments / links.

NHS Choices Alcohol Tracker here.

Doctors have warned, “drinkers should have three alcohol-free days a week if they want to avoid the risk of liver disease,” the Daily Mail reported. It continued that the Royal College of Physicians (RCP) said that the current guidance must be rewritten as it implies that drinking every day is fine.

The new advice from the RCP is part of a submission to MPs on the House of Commons' Science and Technology Committee about current alcohol guidelines. This submission discusses their review of the evidence from 1995 as well as more recent research evidence and alcohol intake guidelines from other countries. The RCP concluded that the current wording of the UK guidelines appears to sanction daily or near daily drinking. It adds that the frequency of alcohol consumption is an important risk factor for the development of alcohol dependency and alcoholic liver disease.

To address what it sees as a problematic lack of emphasis on the frequency of drinking, the RCP suggests that the current advice on safe limits for alcohol intake should be stated in terms of weekly alcohol intake rather than daily unit limits, and that two or three days in the week should be completely alcohol free. It says that men should consume no more than 21 units a week and women should have no more than 14 units, provided the total amount is not drunk in one or two sessions.

The Department of Health (DH) has reportedly said that it has no plans to change its guidance at present. It recommends that men should not regularly drink more than 3-4 units of alcohol a day, while women should not regularly drink more than 2-3 units. ‘Regularly’ is defined as drinking every day or most days of the week. People are also advised to not drink alcohol for 48 hours after a heavy session to let their bodies recover.

Alcohol abuse is associated with an increased risk of liver disease, cancer and other conditions. Read our Live Well pages on alcohol to find out more.

Where is the advice from?

The advice comes from a report by the Royal College of Physicians (RCP). The RCP submitted its report to MPs on the House of Commons' Science and Technology Committee. As such, the advice given is for the government about its policy on recommended alcohol intake limits, rather than being aimed directly at the public.

The RCP believes that government advice on sensible drinking limits can play an important role in dealing with alcohol misuse. It says that it is essential government advice is based on evidence and that it is regularly reviewed. It continues that the last systematic review of the evidence by the government, to which interested parties could submit their views, was in 1995.

The RCP believes that current government guidelines on alcohol consumption could be improved to better reflect the evidence in a number of areas, such as:

• overall levels of consumption that are ‘safe’ or within ‘sensible limits’
• frequency of alcohol consumption
• the physiological effects of ageing
• the balance of the health benefits of alcohol consumption for coronary heart disease against wider alcohol-related health harm

The RCP would also like a clear, independent evaluation of the government’s strategy for communicating its guidelines and the risks of alcohol intake to the public.

What does the RCP advise?

The RCP believes that the current wording of the UK guidelines appears to sanction daily or near daily drinking. It says this is problematic, because the frequency of alcohol consumption is an important risk factor for the development of alcohol dependency and alcoholic liver disease. The RCP cites various studies to support its argument.

It also notes that someone drinking four units a day (the current upper limit for men in the UK) would be classed as a hazardous or high-risk drinker on the WHO’s gold standard tool for identifying people at risk of alcohol-related harm.

The RCP says that these potential problems with the current guidelines could be remedied by moving to a weekly limit and adding the recommendation to three alcohol-free days a week.

It recommends that in order that people keep their alcohol consumption within ‘safe limits’, men should consume no more than 21 units a week and women should have no more than 14 units. It says that most individuals are unlikely to come to harm at these levels, provided the total amount is not drunk in one or two sessions, and that there are two to three alcohol-free days a week. It says that above this limit the risk of death from all causes increases as alcohol consumption increases.

The RCP also notes that these recommendations are a best judgement based on the evidence, and were reached after a number of areas of uncertainty and inaccuracy were taken into account.

The RCP also suggests that recommended limits for safe drinking by older people in the UK require further consideration, as older people may be particularly vulnerable to harm from alcohol due to biological changes associated with ageing. It says that current guidelines are based predominantly on evidence for younger age groups and there is concern they are not appropriate for older people.

40. The current guidelines are based predominantly on evidence for younger age groups and there is concern that current guidelines are not appropriate for older people. The recent report ‘Our invisible addicts’ published by the Royal College of Psychiatrists in 2011, suggests that a ‘safe limit’ for older people is 11 units per week for men, or seven units per week for women. [16]

Ref: http://www.publications.parliament.uk/pa/cm201012/cmselect/cmsctech/writev/1536/ag22.htm

What evidence is this based on?

The RCP’s advice appears to be based on their review of evidence from 1995, and updated with other research evidence published since 1995.

What is current UK government advice?

Official UK government guidance recommends that men should not regularly drink more than 3-4 units of alcohol a day and women should not regularly drink more than 2-3 units a day. 'Regularly' is defined as drinking every day or most days of the week. It is also recommended that people not drink alcohol for 48 hours after a heavy session to let their bodies recover.

http://www.dh.gov.uk/en/Publichealth/Alcoholmisuse/DH_125368

Pregnant women and women trying to conceive should avoid drinking alcohol. If they do choose to drink alcohol, they are advised to not drink more than 1-2 units of alcohol once or twice a week and not to get drunk, to minimise the risk to the baby. The National Institute for Health and Clinical Excellence (NICE), advises women to avoid alcohol in the first three months of their pregnancy in particular, because of the increased risk of miscarriage.

How do the UK guidelines compare to other countries?

The RCP notes that comparing alcohol guidelines between different countries is difficult, as there are differences in the size of standard drinks and units. It reports that a recent analysis by the Australian government found that 15 countries recommended lower limits than the UK for men, and 12 countries recommended lower limits than the UK for women. Six countries recommended higher limits than the UK for men and six countries recommended higher limits than there are for UK women.

The RCP notes that although looking at the guidelines from other countries may be of interest, it is important that UK government guidelines are a considered and expert judgement on the risks of alcohol consumption, based on the scientific and medical evidence.

Where can I get more information?

More information on the effects of alcohol is available from the NHS Choices alcohol pages.

Links to the headlines

Avoid alcohol three days a week, doctors warn. BBC News, October 23 2011

Avoid alcohol three days a week, doctors warn. The Daily Telegraph, October 23 2011

Doctors say alcohol free days needed to protect liver. BBC News, October 23 2011

New guide for safe drinking. The Independent, October 23 2011

Don't drink on 3 days a week. As the liver crisis deepens, leading doctors warn of the dangers. Daily Mail, October 23 2011

Further reading

Royal College of Physicians. The evidence base for alcohol guidelines.

Department of Health Alcohol Advice

OU MSc in Medicinal Chemistry 2011-2013

In February 2011 I started the MSc in Medicinal Chemistry. I've just taken the first year exam. That's why I've only blogged here a few times since February - a bit busy on the course!

First randomised trial specifically for aspirin in cancer

Prof. Sir John Burn

Crabsallover has followed the link between taking aspirin and reducation in Cancer since Peter Rothwell research results in 2010.

reposted from: http://www.nhs.uk/news/2011/10October/Pages/aspirin-cuts-lynch-syndrome-bowel-cancer-risk.aspx

crabsallover highlights, key points, comments / links.

Other studies over the past two decades have suggested Aspirin reduced cancer risk, but this was the first randomised control trial, specifically for aspirin in cancer, to prove it.


Aspirin cuts the risk of bowel cancer in people with inherited susceptibility to the disease,The Guardian has today reported. The newspaper said that a study of long-term aspirin use found it cut the risk of bowel cancer by more than 60% in these individuals.


Prof Sir John Burns (wikipedia) (won a Knighthood 2009) from Newcastle Uni (full list of John Burn publications) on the Today programme (2 min interview with Evan Davis) said 

 Burns mentioned very good research of Peter Rothwell looking at effect on aspirin on heart attack trials. Burns trial results:Out of 250 in trial group 23 cancers occurred in the placebo group but only 10 in the aspirin group.  63% fewer cancers!  In some way aspirin knocks off the cells that are going to be cancerous in a few years time. One theory is that inflammation is involved in cancer progression, aspirins inhibit prostaglandin production. John Burns personal theory is that it is driving programmed cell death (apoptosis). Plants make salicylates (cf aspirin is a salicylate derived from white willow bark) which drive programmed cell death and protects the bark from infection.

Prof Sir John Burn, from Newcastle University, said there were 30,000 adults in the UK with Lynch syndrome.

If all were given the treatment he said it would prevent 10,000 cancers over 30 years and he speculated that this could possibly prevent 1,000 deaths from the disease.

However, there would also be side effects.

"If we can prevent 10,000 cancers in return for 1,000 ulcers and 100 strokes, in most people's minds that's a good deal," he said.

"People who've got a clear family history of, particularly, bowel cancer should seriously consider adding low dose aspirin to their routine and particularly those people who've got a genetic predisposition."

One of the questions asked by the research into aspirin was whether healthy people with no family risks should take the drug.

The lower the risk of heart attack or cancer, the lower the benefit of taking aspirin, yet there are still potentially deadly side effects.

Sir John said that it was a "finely balanced argument" and that he decided the risks were worth it for him.

"I think where we're headed for is people that are in their 50s and 60s would look very seriously at adding a low dose aspirin to their daily routine because it's giving protection against cancer, heart attack and stroke.

"But if they do that they've got to have their eyes wide open. They will increase their risk of ulcers and gastrointestinal bleeds and very rarely they will have a stroke caused by the aspirin."

View John Burns interviewed by Dominic Hughes, BBC

Fergus Walsh, BBC Health Correspondent,  reports having taken aspirin daily for 11 months since the Peter Rothwell trial results.


Those on the John Burn trial took 600mg aspirin daily which is a much bigger dose than the 75 mg that many middle-aged people like me take to reduce their risk of cardiovascular disease. I wrote last year: "If I get an intestinal bleed in a few months time and am taken to hospital needing a blood transfusion, then it will be easy to argue that I got it wrong."

Well, so far so good.

John Burn also looked at other cancers eg womb and found a 50% reduction (Telegraph interview)

John Burn explains his trials and the biochemistry (8min 20s) of Aspirin mechanism to prevent cancers. It might be making faulty cells fall on their sword.

100,000 years ago we used to forage on plants that used salicylates to defend themselves. Now our diet is free of salicyates. Above paper in picture is

J. Burn, P. D. Chapman, D. T. Bishop and J. Mathers (1998). Diet and cancer prevention: the Concerted Action Polyp Prevention (CAPP) Studies. Proceedings of the Nutrition Society, 57 , pp 183-186 doi:10.1079/PNS19980030 (full pdf) 

Another 10 min video on mechanism of action of aspirin (technical)



another presentation by John Burn - trial results and biochem (5min 50s) "as in plants, salicylates initiate apoptosis (programmed cell death) among genetically abnormal stem cells that have yet to become cancer."

OUS827 library search: BOWEL CANCER PREVENTION: ASPIRIN INDUCES COX-2 INDEPENDENT ENDOTHELIAL CELL APOPTOSIS FACILITATING ANGIOGENESIS ARREST.
Detail Only AvailableBy: Johnson, A. S.; Arthur, H. M.; Burn, J.; Wilson, R. G.. Gut, Apr2004 Supplement 3, Vol. 53, pA21-A21, 
Conclusion: Both aspirin and celecoxib caused dose dependent reduction in cell viability, proliferation, and angiogenesis. Celecoxib produced these effects at levels in excess of normal serum levels when it is no longer COX-2 selective. Aspirin induces apoptosis via a COX-2 independent mechanism which may facilitate angiogenesis arrest and play a critical role in limiting tumour growth.

The Lancet Podcast of the 28th October 2011 press conference (20mins) - John Burn & Tim Bishop

taking 600mg / day aspirin gives 60% prevention of cancer - 75mg gives 25% prevention (13 mins) .. but a low dose will avoid a lot of ulcers.. (14 mins).. CaPP3 trials will give clue to best dose 75mg / 300mg / 600mg per day to offset cancer. CaPP3 website now launched!

 Press Release embargo 28th October 2011

The Lancet comments (subscription required)
'The long-term results of CAPP2 are also invaluable for the continued assessment of aspirin for prevention of sporadic colorectal cancer, which is not currently recommended mainly because of concerns about toxic effects and continuing uncertainty about dose and duration.10 With aspirin's well established vascular benefits and recent evidence of benefit for colorectal and other cancers in pooled cardiovascular randomised trials,11 Burn and colleagues' findings might at last tip the scales in favour of aspirin as the chemopreventive agent of choice for many individuals.

Does this long-term follow-up analysis allow a definitive conclusion, say for standard regulatory approval, about aspirin's ability to prevent colorectal cancer? In isolation, no, since the results of the primary analysis were not significant for the ITT (Intention-To-Treat) population. The data strongly support routine use of aspirin, however, for patients with Lynch syndrome as an adjunct to intensive cancer surveillance. As the first randomised trial of aspirin with colorectal cancer as the primary endpoint, CAPP2 also certainly moves us closer to a more definitive answer on aspirin's overall role in the prevention of colorectal cancer. Unfortunately, prohibitive logistics make a randomised trial of aspirin prevention with a colorectal cancer endpoint in a sporadic-risk population unlikely. Therefore, these results from CAPP2 and previous evidence arguably support more general recommendations to consider aspirin for prevention of colorectal cancer in the context of individualised risk-benefit assessments.

Cancer Research UK comment 'People with Lynch syndrome are about 10 times more likely that the general population to develop cancer, particularly of the bowel and womb, and often at a young age.'