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NHS Choices: Behind the headlines   + / -  
last updated: Tue, 09 Feb 2016 00:35:37 GMT

 Mon, 08 Feb 2016 13:30:00 GMT Hope that blood test 'could diagnose five types of cancer'

"A new blood test that detects five different forms of cancer is one step closer to becoming a reality and could save millions of lives around the world," the Mail Online reports. The test looks for abnormal changes in DNA – what is described as a DNA signature.

This laboratory research looked at ways to identify tumour DNA – DNA affected by abnormal cell growth – in blood samples and distinguish it from normal cellular DNA.

The researchers used tissue samples from five cancers – womb, lung, stomachcolon and breast tumours – and compared it with normal healthy tissue.

In brief, they found they could identify the cancerous tissue from a particular DNA signature around a certain gene (ZNF154).

Their tests reveal this test could be fairly accurate at detecting cancer at a concentration of 1% tumour DNA on a background of 99% normal DNA in a blood sample.  

There are many things to consider before any new screening or diagnostic test for cancer is introduced, especially with a "blanket screen" like this.

These issues include how and whether the test improves on current screening or diagnostic methods, as well as looking at the possible harmful effects, such as getting an incorrect positive screen result when you're in fact cancer free, or getting an incorrect negative screen result when you have cancer.  

Where did the story come from?

This study was carried out by researchers from the National Human Genome Research Institutes in the US, and published in the peer-reviewed Journal of Molecular Diagnostics.

The researchers report no sources of financial support and no conflicts of interest.

The Mail Online's reporting of the study is accurate, although its claim that, "a new blood test … could save millions of lives around the world" is prematurely optimistic: this research is in its early stages and has not been tested at a significant population level.

The Daily Telegraph's headline is slightly more restrained: "Blood test to spot five deadly cancers could prevent thousands of deaths". 

What kind of research was this?

This laboratory study examined a possible way of detecting DNA markers for cancer. The researchers report that work on cancer prevention, early diagnosis and treatment has reduced overall cancer death rates by 20% over the past 20 years.

Further advances in screening and diagnosis are, they say, where improvements in survival rates are likely to come. In many cases, the earlier a cancer is diagnosed, the better the outcome tends to be.

Tests that are able to detect genetic information coming from cancerous cells are a possible area for development. Previous research has shown how DNA from a tumour can be found freely circulating in the blood or in saliva, urine and stool samples, for example.

One approach is to look for what is called DNA methylation. This is a signalling method that controls gene activity in a cell, and genes are effectively "switched off".

There are a few specific cancer tests that have already been developed that involve detecting DNA methylation – for example, detecting specific genetic markers for lung cancer in lung fluid, or bowel cancer in stool samples. However, this is still an area of development.

This study builds on the researchers' previous work, where they identified a possible hypermethylation signal near a particular human gene (ZNF154).

This signal was found to come from ovarian and womb cancers and may be found in other cancers, too. This study measured the ZNF154 methylation signal across five different cancers. 

What did the research involve?

The researchers examined cell samples from womb, lung, stomach, colon and breast tumours, and comparison samples of normal tissues from the same organs.

In total, they examined 184 tumour samples and 34 normal tissue samples. They used complex laboratory techniques to analyse cancerous DNA methylation patterns and examine them on a background of normal DNA methylation patterns.      

The researchers then used their findings to identify possible classification methods that could be used in cancer screening. They looked at different ways to characterise methylated bases – the "letters" of DNA (A, C, G and T) – and identified features that could be used to distinguish cancerous tissue from normal tissue.

They then used computational simulation to indicate how reliable these features could be for classifying samples as tumours or normal tissue at various concentration levels, given that in a blood sample, for example, tumour DNA may be present at quite dilute levels.   

What were the basic results?

The researchers found all of the tumour types tested demonstrated hypermethylation at the ZNF154 gene site compared with the normal tissue.

The classification method with the best performance had almost perfect accuracy for distinguishing between normal and cancerous tissue.

Their computational simulation indicated circulating tumour DNA could be detected at a dilution of only 1% tumour DNA on a background of 99% normal DNA. 

How did the researchers interpret the results?

The researchers concluded their findings "suggest that hypermethylation of the ZNF154 [gene site] is a relevant biomarker for identifying solid tumour DNA and may have utility as a generalisable biomarker for circulating tumour DNA". 

Conclusion

This is very early-stage laboratory research that aimed to explore new avenues that could detect and diagnose cancer earlier – and hopefully ultimately lead to earlier and more successful treatment, and so better cancer survival rates. 

The study indicates taking blood samples and detecting DNA methylation from tumours could be one possible early screening or diagnostic method, and shows this technique's use for indicating womb, lung, stomach, colon and breast tumours.

However, there are likely to be many more stages of research necessary to build on these findings and check how reliable the test could be for different subtypes of these cancers, and also whether it could be used for other types of cancer.

Even then, there are many things to be taken into account before considering introducing any new screening or diagnostic test for cancer, including how and whether it improves on current screening or diagnostic methods.

For example, the media has highlighted the benefits of a blood test being "non-invasive", but current screening tests for bowel and breast cancer – taking stool samples and using mammograms, for instance – are also non-invasive.

Possible harmful effects also need to be considered, such as getting an incorrect positive screening result when you're in fact cancer free (false positive), or getting an incorrect negative screen result when you do have cancer (false negative). There is also the question of whether screening for certain cancers could seem to lead to improved survival time.

While early diagnosis often leads to a better prognosis, this is not the case for all cancers. Some people, for example, may face the emotional trauma of living with the knowledge that they have cancer for longer, but there still isn't an effective treatment to cure them.

In this situation, longer survival time might not actually mean better survival – it just means longer survival with a cancer diagnosis.

Ultimately, screening for any disease is no magic bullet, especially a potential "blanket screen" like the method outlined in this study.

Links To The Headlines

New blood test could diagnose FIVE different cancers 'without the need for invasive biopsies, saving millions of lives'. Mail Online, February 5 2016

Blood test to spot five deadly cancers could prevent thousands of deaths. The Daily Telegraph, February 5 2016

Links To Science

Margolin G, Petrykowska HM, Jameel N, et al. Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development. The Journal of Molecular Diagnostics. Published online February 5 2016

 Fri, 05 Feb 2016 12:00:00 GMT Could statins treat common cause of vision loss?

"Statins could be miracle cure for blindness," reports the Express, following a new study into dry age-related macular degeneration (AMD), one of the leading causes of blindness in adults.

AMD is a condition caused by damage to part of the back of the eye called the macula. It’s called "dry" or "wet", depending on whether fragile blood vessels have developed to try to repair the damage. There are treatments for wet AMD, but none for the much more common dry form.

After promising results in the case of a single 63-year-old man, the researchers gave a high-dose of daily statin (80mg atorvastatin) over a year to 23 adults over 50. Ten of the group experienced some vision improvement and a reduction in fatty deposits called drusen in their eyes, but vision in the remaining 13 patients continued to get worse.

The study had several limitations, but this is understandable, given the early stage of this research. Most notably:

  • the study was very small
  • treatment was non-randomised
  • treatment was not concealed (blinding), so people knew what they were taking and why
  • there was no control group, so the results weren't compared to people taking no medication or "dummy" medication (placebo)
  • vision improvements reported by some participants might have been due to chance

The researchers also point out that dry AMD can vary a lot between people, so it's unlikely that statins would be effective for everyone with the condition.

Overall, there were signs that statins improved vision in dry AMD, but it didn't work for most people. It's not possible to know whether statins could be a "cure" for AMD without more research.

Where did the story come from?

The study was carried out by researchers from Harvard Medical School and the University of Crete, and was funded by Yeatts Family Foundation, the Mass Eye and Ear Neovascular AMD funds, the Loefflers Family Foundation, and the Research to Prevent Blindness Foundation.

The study was published in the peer-reviewed science journal EBioMedicine, and is free to read online.

Generally, the media over-inflated the results and didn't discuss the numerous and important limitations of this research.

Much of the coverage suggested statins may be the miracle cure for blindness in general. However, the study was specifically targeting a particular type of vision loss and potential blindness: dry AMD with large soft drusen deposits.

Other types of dry AMD exist, as well as wet AMD. The researchers themselves said that it is unlikely that statins will be effective across the broad range of dry AMD, as the condition is quite variable.

What kind of research was this?

This was an open-label, small prospective study looking at the effects of high-dose statins on progression of dry AMD.

Small studies like this are useful to test a hypothesis – in this case, that high-dose statins might help dry AMD – but they only represent an early phase in treatment development. These studies may throw up promising results that are subsequently disproven using bigger, better-designed studies.

While it's encouraging when these types of study show benefits, there are no guarantees the benefits will be confirmed when tested more rigorously.

What did the research involve?

The study recruited 26 patients over the age of 50 with a dry AMD diagnosis, with many large soft deposits of drusen causing disruption to cell layers of the back of the eye.

They were all given a high-dose (80mg) of a statin called atorvastatin every day for 12 months, and knew what they were taking and why.

Each had comprehensive eye exams at the start of the trial and every three months after to monitor changes, including the size and number of drusen deposits. Clarity of vision was measured every six months by reading letters at ever-decreasing sizes through corrective lenses, similar to the classic Snellen eye test sometimes done at opticians.

As dry AMD is a progressive disease, they were looking for signs the disease was being slowed, halted or reversed – any of these would be an improvement over current treatment options.

The study also reported the experimental case of a 63-year-old man with dry AMD who took progressively higher doses of atorvastatin than the target 80mg per day in response to deteriorating visual clarity.

What were the basic results?

Of the 26 participants, 23 made it to at least the end of the first 12 months: 10 from Europe, 13 from the US. Three exited the study early: one because of cramps, one because of muscle aches, and one because they felt the drug was inducing hair loss.

Daily high-dose atorvastatin for a year resulted in fewer drusen deposits in 10 of the 23 participants (43%), and near-complete disappearance in eight people.

Ten of those taking atorvastatin improved their visual clarity, by an average of 3.3 letters on a letter chart. This compared to an average loss of 2.3 letters over the same period for those in whom it didn't work. These differences however, were not statistically significant, meaning it may be a chance finding.

The case of the 63-year-old man was much more dramatic. After six months on 80mg daily atorvastatin, his visual clarity improved by 12 letters and the drusen deposits had completely disappeared, leaving him with 20/20 vision.

How did the researchers interpret the results?

The researchers concluded that: "High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) [drusen deposits] and improvement in visual acuity [clarity of vision]" adding, "Confirmation from larger studies is warranted".

Conclusion

The difference between the dramatic improvement seen in the case study of the 63-year-old man and the comparatively modest, or lack of, effect seen in the 23 taking part in the trial shows the limitations of studying small numbers of people, and the current uncertainly about the effects of this treatment.

There is large variability in small groups, which doesn't tell us whether the treatment will help most people. The way to solve this is to study lots more people. This helps to smooth out the natural variability in people's responses to the same treatment and can highlight groups more or less likely to benefit. These groups can be studied further to figure out why the variation exists and potentially discover other ways to help more people benefit.

Other limitations include that this study was very small, treatment was not randomised, there was no treatment concealment (blinding), there was no control group, and the visual improvements reported between treatment responders and non-responders might have been due to chance.

The study also focused on people with dry AMD with a high number of large soft drusen deposits, which is a sub-group people with dry AMD. These are all limitations, but understandable ones given the very early stage of this research.

As AMD is so variable, the researchers point out that it's unlikely that statins would be effective for everyone with the condition.

The good news is that there were some signs statins improved vision in dry AMD. However, there was a lot of variation and only 43% of those in the trial experienced an improvement in their sight.

Larger studies are needed to look into statins as a possible treatment for AMD. It's not currently advisable to take statins for dry AMD, as there isn't enough evidence.

Links To The Headlines

Statins could be miracle cure for blindness: Pills could destroy fats that clog the eye. Daily Express, February 5 2016

Could statins help restore vision? Drugs found to clear away deposits that cause blindness in the elderly. Mail Online, February 4 2016

Statin drug could restore eyesight to patients with common form of blindness, say scientists. Daily Mirror, February 4 2016

Statins could reverse most common form of blindness. The Telegraph, February 4 2016

Links To Science

Miller JW, Vavvas DG, Daniels AB, et al. Regression of some high-risk features of age-related macular degeneration (AMD) in patients receiving intensive statin treatment. EBioMedicine. Published online February 4 2016

 Thu, 04 Feb 2016 00:00:00 GMT Smoking bans linked to fewer heart attacks and strokes

The ban on smoking indoors in public places "has helped save the lives of passive smokers," says the Daily Mail.

The headline refers to a review of the effects of smoking bans in 21 countries, including England and Scotland. This found fewer admissions to hospitals for heart attacks and strokes following smoking bans. However, the bans didn't appear to encourage more people to stop smoking.

Some studies included in the review found a bigger reduction in heart attacks and strokes among non-smokers – who are no longer exposed to smoke in public places – than smokers, who are still exposed to their own smoke.

The difficulty with research into smoking bans is that you can't carry out the "gold standard" of research: a randomised controlled trial. Instead, we have to rely on observational evidence – for example, looking at trends in hospital admissions for heart attacks before and after a ban is introduced.

It's hard to prove that smoking bans have led to lower hospital admissions, rather than other things, such as putting tobacco prices up. But this research suggests they have, particularly for non-smokers.

Where did the story come from?

The study was carried out by researchers from the Cochrane Tobacco Addiction Group, which is part of the Cochrane Collaboration of international healthcare researchers. It was funded by the Health Research Board Ireland and University College Dublin. The study was published in the peer-reviewed Cochrane Database of Systematic Reviews on an open-access basis, so it is free to read online.

The Sun, Mail Online and The Daily Telegraph focused on results from the smoking ban in England, which was introduced in 2007. While they were reported accurately, these results were published in the British Medical Journal (BMJ) in 2013, so are not particularly new. The Guardian gave a good overview of the research, including links to the original studies.

What kind of research was this?

This was a systematic review of all the studies previously published on the effects of smoking bans on health. Systematic reviews are the best way to get a balanced picture of all the evidence on a topic. However, they are only as good as the studies they include.

In this case, there were no randomised controlled trials, so the researchers had to rely on observational studies of varying quality.

What did the research involve?

This research was an update of a previous systematic review of the evidence around smoking bans, published in 2010. Since then, more countries have introduced smoking bans and more studies have been published.

Researchers searched databases of published research, looking for all relevant studies that met their criteria. They then examined all the studies to record their methodology, results and assess the study for risk of bias.

Usually, Cochrane reviews carry out a meta-analysis, where they pool the data to give overall results from all the studies. Because of the different types of research they found, they were unable to do this for this review. Instead, they grouped together studies looking at the same health outcomes, then summarised the results for each group.

What were the basic results?

Researchers found 77 studies and looked at the effects of a smoking ban on:

  • cardiovascular health (mainly heart attacks and strokes)
  • respiratory health (mainly asthma and chronic obstructive pulmonary disease, or COPD)
  • the health of newborn babies
  • numbers of deaths from smoking-related diseases
  • numbers of people who smoked, plus quit rates and tobacco consumption

They found "persuasive" evidence from 33 out of 43 studies that fewer people were admitted to hospitals with heart attacks and unstable angina, and evidence from five out of six studies that fewer people were admitted with stroke. Some studies found that non-smokers benefited from a bigger reduction in the incidence of heart attack and stroke.

The review also found national rates of smoking-related diseases (including heart disease) went down after smoking bans were introduced, and continued to fall. Eight out of 11 studies showed a reduction in deaths from smoking-related diseases.

The picture was mixed for respiratory health, with conflicting results from the 21 studies reviewed; some found a reduction in COPD or asthma admissions, but others did not.

The researchers found pregnant women were less likely to smoke after bans had been introduced, and some studies found fewer babies were born prematurely or with low birth weight. However, they say the quality of the evidence was too low and the study results were too conflicting to be sure.

The evidence was also unclear about the effect smoking bans had on how much people smoked, and how many smoked. While some studies showed a dip in smoking and an increase in attempts to quit just before and shortly after a smoking ban was introduced, these reductions didn't last.

As most countries were already showing a trend away from smoking, it's difficult to determine whether the bans played a part. Other factors, such as the price of tobacco and economic outlook in a country, might have affected the results.

How did the researchers interpret the results?

The researchers said the results gave "more robust support" for their previous conclusions that smoking bans were linked to better health outcomes. "There is moderate quality evidence that countries and their populations benefit from enacting national legislative smoking bans with improved health outcomes from reduced exposures to passive smoke, specifically cardiovascular disease," they said.

However, they added that the evidence for fewer deaths from smoking-related diseases was "low quality".

Conclusion

There is no doubt that tobacco smoking harms health and causes a great deal of disease and death. The World Health Organization (WHO) estimates that tobacco is responsible for one in 10 adult deaths worldwide.

The question is whether smoking bans can help reduce the harm caused by tobacco. This summary of research suggests they can, particularly for people who are non-smokers. While it's hard to get good-quality evidence about the effects of smoking bans, comparisons of data from hospitals and national registries before and after a ban is helpful.

However, we can't be sure the effects being measured are solely down to the smoking ban. For example, bans on trans fats in foods in some countries could also have contributed to a drop in heart attacks and stroke. However, it's useful to have information from lots of different countries, all showing similar trends over time.

The evidence around the numbers of people who stop smoking after a smoking ban is disappointing, but the researchers point out that smoking bans are only one way to encourage people to quit.

If the effects of a smoking ban are simply to protect people who don't smoke from the harmful effects of tobacco, that is still a big improvement.

Read more information and support about how to give up smoking

Links To The Headlines

Smoking ban sees 40 per cent cut in heart attacks in UK since 2007 law was introduced. The Telegraph, February 4 2016

Smoking bans reduce harm from passive smoking, study finds. The Guardian, February 4 2016

Heart attack rates have fallen by 42 per cent since the smoking ban in 2007. The Sun, February 4 2016

Ban has helped save the lives of passive smokers: Number of heart disease cases has dropped 'significantly' following introduction of laws. Mail Online, February 4 2016 

Links To Science

Frazer K, Callinan JE, McHugh J et al. Legislative smoking bans for reducing harms from secondhand smoke exposure, smoking prevalence and tobacco consumption. Cochrane Database of Systematic Reviews. Published online February 4 2016.


 

 
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