Oesophageal cancer rates are on the rise

Many people have never even heard of cancer of the oesophagus – a form of cancer affecting the pipe that connects the mouth to the top of the stomach.

Yet rates of this cancer are on the rise.

According to new figures we released today, the rise is most rapid in men – among whom a particular form of the disease, called adenocarcinoma, is one of the fastest rising cancers in the UK.

But what’s causing this rise? And – most importantly – what can be done about it?

In this post, we’ll look at what’s going on, and whether our lifestyles might be behind the rise.

And we’ll also meet a heroic team of marathon-running medics who are doing everything they can to change the picture for patients diagnosed with oesophageal cancer – one of the hardest forms of cancer to treat successfully, but one which generally gets little attention in the media.

What is oesophageal cancer?

Every day around 23 people in the UK are diagnosed with oesophageal cancer, about eight out of ten of whom are aged 60 or over, and about two thirds of whom are men.

As with many types of cancer, things in our ‘modern’ lifestyles can affect the risk – the disease is more common among people who smoke, drink heavily, are overweight or obese, or who eat a diet low in fruit and veg. And people with long-term persistent heartburn – something that can also be linked to obesity – have a higher risk too.

• Watch this video on YouTube

In general, survival rates for cancer of the oesophagus are low compared with other cancers – partly because the disease is often diagnosed at a late stage.

Overall, for every 100 people diagnosed with the disease, only around 13 are alive five years later. But when the disease is diagnosed in its earliest stage, this figure rises to about 80 out of 100. Sadly, only a small proportion of patients are diagnosed this early.

Treatment for early-stage disease usually involves a course of chemotherapy to shrink the tumour, followed by surgery, and aims to cure it. For later stage disease, treatment is aimed at controlling the disease and alleviating symptoms.

If you want to find out more, there’s detailed information about the disease on our  website, some statistical ‘key facts’, as well as info about symptoms and treatment.

Different types, different causes?

There are two main types of oesophageal cancer

There are two main types of cancer that affect the oesophagus, called squamous cell carcinomas and adenocarcinomas, and the evidence suggests they have different triggers.

Squamous cell carcinomas seem to be linked to smoking and drinking. Rates have remained roughly constant in men and women since the mid 90s.

Adenocarcinoma – the form that’s on the increase – is also linked to smoking, but less strongly than squamous cell carcinomas. But it also seems to be linked to long-term acid reflux (heartburn), which itself is more likely if you’re overweight or obese.

There are a few theories about how heartburn can lead to cancer. The main one is that having long-term, persistent heartburn causes chronic inflammation in the cells lining the oesophagus. As well as causing them to divide more rapidly – this inflammation also seems to cause tell-tale chemical changes to the DNA inside them.

These changes, researchers think, lead to a condition called Barrett’s Oesophagus, which – in a small minority of people – can go on to develop into cancer.

People diagnosed with Barrett’s Oesophagus are offered regular screening with an endoscope (a camera that goes down your throat) to spot early signs of cancer.

Increasing rates

As you can see from the graph below, rates of oesophageal cancer in men have risen by almost 60 per cent over the last 30 years, and by 10 per cent in women – but why?

When we looked at the breakdown of what was causing the increase, we found something surprising: it was almost entirely down to rising rates of adenocarcinoma in men.

Oesophageal cancer is on the rise

Why would this be?

One culprit could be increasing rates of heartburn. According to a recent Norwegian study, discussed here on NHS Choices, “the number of people experiencing at least one acid reflux attack a week has risen from 11.6 per cent to 17.1 per cent in just over a decade, while those suffering severe symptoms is up from 5.4 per cent to 6.7 per cent”.

Only a small proportion of people with heartburn will go on to get oesophageal cancer, but if this rise in Norway reflects the UK situation, it’s worrying nevertheless.

Oesophageal cancer is more common in people who are overweight or obese

And if heartburn is really on the rise, what’s the reason?

One obvious cause could be the nation’s growing waistline – in recent decades, rates of overweight and obesity have slowly but steadily climbed. And there’s solid evidence linking obesity to adenocarcinomas of the oesophagus.

However, intuitive as it may sound, researchers don’t yet know for definite whether heartburn caused by rising obesity is leading to more oesophageal cancer – it wouldn’t explain the differences in rates between men and women (as the rate of increase in obesity has been approximately equal in men and women).

So why the increase in adenocarcinoma in men? We can’t be sure, and there’s a lot more work to be done here too. However, we have some theories.

One idea is that women’s hormones might play a role in protecting them against the disease, and there’s some evidence for this.

Another idea might be that the type of obesity that’s more common in men, called abdominal obesity, might be linked to increased rates of oesophageal cancer (it does increase the risk of certain other cancers). However, there’s no evidence yet to show whether this type of obesity is especially linked to oesophageal cancer, so at this stage this remains just an idea.

Early diagnosis is important

Whatever the reason, we know that early diagnosis makes a difference. Which brings us to two more issues:

Firstly, over-the-counter heartburn medicines – Rennies, Zantac and the like. These are readily available, so people with long-term heartburn sometimes try to control things by popping a pill every now and again – rather than seeing a doctor.

Secondly, we know that people don’t always know a huge amount about cancer symptoms (and men less so than women) – which in the case of oesophageal cancer are difficulty swallowing food, or food feeling like it’s got stuck in your throat, as well as long-term heartburn. So people may not seek help from a GP for something that could be a sign of a serious problem.

In short – don’t ignore any changes to your body that aren’t normal for you – either long-term heartburn or food getting stuck in your throat.

Do go and see your GP, and get checked out. It’s unlikely to be cancer, or lead to cancer, but it’s always better to be safe.

What can be done?

Help support The Cancer Marathon and raise funds for research

Research is the key to progress against cancer, and there are three key areas where research can make a difference:

• We need to understand more about what raises the risk of oesophageal cancer and how we can help people live healthy lives to reduce the risk.
• We need to improve the way we (as a society) diagnose oesophageal cancer, so that people with the disease get to a specialist earlier.
• We need to find better ways to treat the disease, especially at a late stage.

At Cancer Research UK we’re funding research in all these areas. For example, we’re funding a very promising trial led by researchers in Cambridge, looking at whether collecting cells from the oesophagus using a device called a cytosponge can spot early signs of the disease.

And one of the most exciting projects we’re involved with is our work as part of the International Cancer Genome Consortium (ICGC) – an international project to map all the genes involved in several different types of cancer, to look for clues for new treatments and better understanding. Our scientists are bringing their gene-hunting expertise to bear on oesophageal cancer, and we’re expecting their first round of results to emerge later this year.

(You can read more about their work in our oesophageal cancer Research Leaflet).

Running for progress

But we want to leave you with the exciting and inspirational story of a team of medics from Southampton, who want to make a difference for people affected by this terrible disease.

They’re currently training to run the New York Marathon in November, both to raise awareness of oesophageal cancer, and to raise money to fund our ICGC genetics project.

We’ll be following their progress over the coming months, but here’s the first instalment of their story – The Cancer Marathon – which also follows their patients as they go through treatment for oesophageal cancer.

This is something surgeon Tim Underwood (one of the runners) often describes as “like running a marathon without any training”.

• Watch this video on YouTube

You can keep up with their progress on their blog, www.thecancermarathon.org, or follow research surgeron Tim Underwood on Twitter at @timthesurgeon.

And if you want to support their marathon effort, you can do so over at JustGiving, where their page is www.justgiving.com/thecancermarathon. They’re trying to raise £100k, so every donation will count, no matter how small.

Henry

Read our news digest

• In one of the week’s biggest health stories, the Government announced that e-cigarettes are to be regulated as medicines. Our news story has more detail, and we wrote this blog post about why we think this is a good idea.
• Our researchers showed that testing women for the human papillomavirus (HPV), rather than using the traditional cervical screening test (which looks for abnormal cells) could prevent an extra 600 cases of cervical cancer a year in England. The Telegraph covered the research, and here’s our press release.
• The US Supreme Court ruled that human DNA can’t be patented. The BBC wrote about the decision and what it could mean for research and innovation, while the Guardian had this response.
• Patients say they get better care at hospitals with more specialist nurses. Our news article has more information.

• Our researchers discovered genes that control shape changes in melanoma skin cancer cells, which appear to allow them to wriggle free and spread around the body. Here’s our press release.
• Millions of patient records with details about cancer treatments have been compiled into a single cancer database for the first time (here’s our news story). Its early days, but this could be a step towards understanding how to deliver better cancer care.
• Channel 4’s Dispatches on Monday looked into claims that new diabetes drugs could increase the risk of pancreatic cancer. NHS Choices also looked at the claims.
• Researchers in Germany found a new way to exploit the differences between cancer cells and normal cells that could lead to new clinical trials. The team focused on cancer cells that lack a crucial ‘triage’ molecule called ATM, which is normally involved in directing a cell’s response to damage. Our news story has more info.

• Here’s an article on WebMD about the stigma of lung cancer.

• This Express article about using mouse ‘avatars’ to help find new cancer treatment is really interesting.

• We spotted this excellent documentary on Al Jazeera, about overseas cancer clinics that offer patients false hope.

• Headlines in the Daily Mail and Telegraph claimed that breast cancer screening doesn’t cut cancer deaths. But the study in question only looked at trends that overemphasise the peaks and troughs of death rates in a single year, rather than concentrating on the average death rate over several years. The most robust research shows breast screening is effective at cutting deaths, though also comes with risks. NHS Choices also had this analysis.

• This accompanying Telegraph article about the challenges doctors and patients face in making decisions about screening is well worth reading, and raises the broader issues around how to deal with uncertainty in medicine.

And finally

• The Independent reported that “successful women may be more likely to develop breast cancer” and “stress at work could be to blame”. But women shouldn’t be alarmed by this study. The balance of scientific evidence shows that stress, including job stress, doesn’t seem to be linked to breast cancer risk, though it could lead people to have less healthy lifestyles – like smoking, or drinking more alcohol – which can raise the risk of cancer.

Dr Marianne Baker, in the lab

How do our bodies form new blood vessels? This is a key question in cancer research, as tumours need to develop a new blood supply to grow.

Last summer, Dr Marianne Baker finished her Cancer Research UK-funded PhD in the Centre for Tumour Biology at the Barts Cancer Research UK Centre in London, focusing on a small but potentially significant part of this question.

In May this year, her findings – focusing on some of the molecules involved in new blood vessel growth – were published in the journal PLoS ONE.

In this guest post, she explains what she did, what she found, what it means, and what happens next.

A sticky subject

Staying in one piece is very important for any organism that consists of more than one cell (that’s everything except bacteria and things like amoebas). Our cells obviously have to stick to each other and to the non-cell parts of the body (bones and all the other stuff) or we’d simply fall apart.

Researchers call this ‘cell adhesion’, and it was this that was the focus of the lab in which I did my PhD, under the supervision of Professor Kairbaan Hodivala-Dilke.

Studying cell adhesion is, basically, working out exactly how cells stick to and interact with each other and their environment. To do that, cells need their surfaces to be ‘sticky’ in some way – just like a smooth, round ball won’t stick to anything unless you cover it in Velcro and throw it at a receptive surface.

Cells’ stickiness comes from proteins that sit on their surface, often spanning each cell’s surrounding membrane like a sea monster loops in and out of the water. These proteins can make contact with similar proteins on other cells, holding together and keeping our bodies and organs in the right shape, and place.

‘Sticky’ adhesion proteins weave in and out of a cell’s surface like a sea monster

Check the pipework

But as well as giving our bodies shape and form, this stickiness is also important for our internal ‘plumbing’ – the circulatory system, which carries blood to our organs, providing life-sustaining oxygen and nutrients.

Studying exactly how tumours subvert the body’s plumbing is a key focus for researchers, because cancers also require their own blood vessels to get nutrients and grow (you can read more about this process – known as angiogenesis – in a previous post I wrote).

Researchers have known for decades that blood vessels in a tumour are abnormal and leaky, and that this can be both good and bad for the tumour. On the one hand, it can get more oxygen and nutrients in some regions of the tumour. But on the other, it can lead to areas of poor blood supply – leading to regions with a lot of cell death (called necrosis).

This can be good and bad for patients, too – good, because more chemotherapy drugs can leak out in the tumour, but bad because the drugs don’t penetrate the whole of it due to the poor blood flow. Low-oxygen areas are also more resistant to radiotherapy, because the treatment needs oxygen to work.

So, understanding the intricate details of what affects blood vessel growth, and the integrity (or permeability) of blood vessel walls can actually help us design different types of treatment that might be more effective.

This is a bigger job than we thought

The blood vessels in our bodies are lined by specialised cells called endothelial cells, which stick to each other via cell-cell contacts of different types, depending on which “sticky proteins” are involved.

One type of endothelial cell-cell contact is called a tight junction – and that’s what I looked at in the latter part of my PhD, and my results are reported in the paper that we published last month.

Tight junctions are made up of several different types of proteins, including Claudins, which are transmembrane surface proteins (the sea monster-type ones).

The type of claudin you find in the junctions depends on what type of cell you look at, and until recently it was thought that Claudin-5 was the main Claudin sticking our endothelial cells together.

However, there are members of the Claudin protein family whose functions are still shrouded in mystery – and if we’re going to properly understand how to target blood vessels to treat cancer, we need to understand the proteins involved.

So for part of my PhD, I focused on a little-understood Claudin called Claudin-14, which is known to be involved in a certain form of deafness.

But, we wondered, is it involved in blood vessel growth too? So far the only other clue came from research linking higher levels of Claudin-14 protein to the shape endothelial cells grew in.

Could we find out more?

When Claudin-14 supplies are at 50 per cent

To start to understand how Claudin-14 works, we worked with three types of mice:

1. normal mice, which carry two copies of the gene that makes Claudin-14 (called ‘wild-types’);
2. “heterozygous” mice (Hets) who have been genetically altered to carry just one copy,
3. and “Null” mice, who have no copies of the Claudin-14 gene.

Comparing tumour growth and angiogenesis in these mice would allow us to work out what role – if any – Claudin-14 was playing.

First, we looked at the endothelial cell tight junctions in the blood vessels from tumours the mice had developed. Usually where cells stick together you can see nice neat lines of tight junction proteins:

Tight junctions in ‘normal’ epithelial cells

But in blood vessels from tumours in Het mice, we found a lot of junctions were disrupted:

Tight junctions in endothlial cells lacking a copy of the gene for Claudin-14

We also saw that small, drug-sized molecules tended to leak out of the vessels more in Het tumours, and that low-oxygen areas were actually harder to spot in those tumours. That seemed strange, but on closer inspection, there actually seemed to be more blood vessels in the tumours from Het mice.

It was also apparent that a greater proportion of those vessels were closed, or seemed to be under-developed and non-functional. Could it be that there were more endothelial cells, but fewer working blood vessels?

To find out more, I grew some blood vessels from bits of the aorta (the big blood vessel that comes out of the heart) in plastic Petri dishes, and found that the Het mice indeed produced more. And when I grew individual endothelial cells in the lab, they divided more frequently too.

So it looked like only having one copy of Claudin-14 caused problems for the integrity of newly grown blood vessels, and more rapid growth, maybe in a kind of feedback loop.

This clearly shows a role for Claudin-14 in angiogenesis, and suggests that interfering with its function makes tumour blood vessels more ‘leaky’ (although it didn’t affect tumour growth overall).

What about the nulls?

But what about the mice that had no Claudin14? Surely their vessels would be even leakier, their endothelial cells grow even faster?

And here’s the paradox of Claudin-14. Because it turns out that, with everything I looked at, the nulls all looked the same as the wild-types. No effect. Nada. Zilch.

Why this would be the case – seeing an effect when one copy of a gene was missing, but nothing when both were – has left us completely stumped.

We assume it’s due to a phenomenon called compensation, where similar molecules fill in for the role of the one that’s missing (Like when you’ve run out of butter for the cake so have to use some butter-like imitation substance from that tub at the back of the fridge: It does the job, it’s not quite right, but it’ll do).

The go-to candidate for this compensation was Claudin-5, as we knew from the work of others that it could be found in endothelial cells.

But a colleague checked Claudin-5 levels in our samples, and they were the same in all three situations; whether Claudin-14 was present in two gene copies, one, or none.

So we still don’t know – but that’s the nature of scientific research, you put together a few small pieces of a much bigger jigsaw, laying some groundwork that perhaps someone else can build on in the future.

So what next?

I’m no longer in the lab, but now this research has been published, other researchers can access my results, and maybe one day there will be some answers to these “what the hell is going on?!” questions.

It’s nice to think that one day this research could be looked at by another scientist, facing their own challenging questions, and it might help answer them. Or even, perhaps, that this knowledge might one day benefit cancer patients, or even another condition we don’t yet know to be related.

It’s a long pipeline, and there are no guarantees, but even better than satisfying curiosities is the fact that I’ve played a part in the collective efforts of researchers and medical professionals, the likes of which have been key in improving cancer treatments and the lives of cancer patients, and will continue to do so in the future.

Marianne

Reference:

• Baker M., Reynolds L.E., Robinson S.D., Lees D.M., Parsons M., Elia G. & Hodivala-Dilke K. (2013). Stromal Claudin14-Heterozygosity, but Not Deletion, Increases Tumour Blood Leakage without Affecting Tumour Growth., PloS one, PMID: 23675413

The industry continues to have a role in tobacco smuggling

The taxman has come under fire in the past week, thanks to a new report from the National Audit Office that brands HM Revenue and Customs’ efforts to curb tobacco smuggling as “disappointing” and “too weak”.

The media spotlight fell – perhaps unfortunately – on the fact that the HMRC is ‘missing cigarette smuggling targets‘.

Unfortunate because, for us, the real headline – and indeed, the other significant focus of the report – is the tobacco industry’s continuing role in tobacco smuggling, which hinders efforts to tackle the illicit trade.

Helping people quit smoking, or not start, is a cornerstone of our work on cancer prevention. The reason is simple: tobacco is by far the UK’s single greatest cause of preventable illness and early death and causes a staggering one in four cancer deaths.

And as well as cheating the UK of tax revenue, tobacco smuggling undermines tax and pricing strategies that are an important part of the country’s strategy for reducing tobacco’s deadly toll.

In this post, we’ll look at recent trends and developments in tobacco smuggling, and see how industry’s claims about illicit trade should be taken with a very large pinch of salt.

A history of smuggling

As the graph shows, cigarette smuggling hit its peak in 2000-2001, when it made up 21 per cent of the total UK market (and 61 per cent of hand-rolling tobacco).

When HMRC launched its first Tackling Tobacco Smuggling strategy in 2000, most large cigarette seizures consisted of genuine UK brands that had been exported by tobacco companies to overseas markets but subsequently smuggled back into the UK with no tax paid.

Following court cases and reports by the Health Select Committee and the Public Account Committee major UK tobacco manufacturers agreed in 2002 to do more to tackle smuggling, by each signing up to a ‘Memorandum of Understanding’ with the HMRC.

Crucially, they agreed to do more to control the ‘oversupply’ of cigarettes to certain countries, which had been fuelling the illicit trade. For example, in 1997, Andorra was supplied with 3.1 billion cigarettes – equivalent to every Andorran smoking seven packets a day – most of these were then smuggled back to the UK.

Four years later, these ‘Memorandums’ were then reinforced by new laws (as part of the Finance Act, 2006), which put legal provisions in place, including fines of £5m, for tobacco manufacturers who failed to clamp down on smuggling.

National Audit Office findings

But despite these promises and regulations, today’s National Audit Office report criticises the tobacco industry for continuing to oversupply markets with large quantities of tobacco:

HMRC’s latest estimate, for 2011, is that the aggregate actual supply … of hand-rolling tobacco to some countries exceeded legitimate demand by 240 per cent. Supply of genuine products to high-risk markets remains higher than HMRC’s analysis of local demand, particularly for certain brands of hand-rolling tobacco, although manufacturers dispute this.

If the tobacco industry continues to have such a laissez faire attitude to the oversupply of its products, enforcement officials are faced with the archetypal Sisyphean task.

We’re also concerned with the methodology, data collection and reporting practice used in tobacco industry-funded or commissioned reports about the illicit trade. They often infer that the illicit market is much bigger than the evidence from HMRC shows.

Declining market share

But the official figures clearly show that the illicit tobacco market has in fact decreased substantially between 2001 and 2011 – from 21 per cent to 9 per cent for cigarettes, and from 61 per cent to 38 per cent for hand-rolled tobacco – an irrefutable downward trend.

As a result, the Advertising Standards Authority recently ruled that a series of advertisements from Japan Tobacco International which claimed that: “The black market in tobacco is booming” breached the advertising code on misleading advertising and substantiation.

But tobacco industry claims have not only fallen foul of this country’s regulators. Internationally, they continue to fall foul of the rules too.

Global issues

In 2012, Japan Tobacco International was accused of smuggling activities in the Middle East, and is now under official investigation by the European Anti-Fraud Office, OLAF. The investigation has focused on cigarettes that were allegedly sold to a black-listed associate of the brother of Syrian President Bashar al-Assad. It is suspected that these cigarettes are either being used to pay military salaries or being sold at a higher price, thereby generating profit used to fund al-Assad’s regime.

And just last week The Times reported that British American Tobacco’s (BAT’s) agent for cigarette sales in the Horn of Africa of almost 25 years is being pursued by officials in Djibouti, having been accused of clandestinely shipping BAT’s Benson & Hedges cigarettes into the country from Somalia without paying duty. The same individual was issued with a ‘red notice’ by Interpol, in response to accusations of involvement in a terrorist attack.

The Times reports that BAT is understood to have refused to cut its connection to the individual and still uses him as an agent in other countries.

Standardised packaging and the illicit trade have no relationship

The tobacco industry has continued to advance a myth, attempting to link tobacco smuggling with plans for plain, standardised packaging (something Cancer Research UK has been campaigning for), by committing millions of pounds to adverts which have repeatedly breached advertising codes, and funding front groups, who have come under fire for failing to declare their vested interests to parliament.

In reality, the halving of illicit tobacco’s share of the market has coincided with a decade of progress in implementing more comprehensive tobacco control measures including tax increases. The idea that measures designed to reduce smoking will increase the illicit trade simply doesn’t add up.

The Trading Standards Institute, a representative from the EU anti-fraud office, and police involved in combating tobacco smuggling in the North of England say that the introduction of standardised packaging is likely to have little or no significant impact on the level of illicit trade.

Richard Ferry, a trading standards officer who works on the ground in the North East, wrote on this blog that arguments that link standard packs with an increase in the illicit market simply don’t make sense.

The Police and Crime Commissioner in Greater Manchester has also publicly dismissed claims that standardised packs would increase the illicit trade and has urged their introduction to protect children from the harms of tobacco.

The Government should follow Australia and echo the ambitions of The Republic of Ireland, Scotland and New Zealand by committing to legislation for standardised packaging in the UK, and give parliament the chance to vote on the issue.

Standard packs can be a public health success for the UK, which builds both on progress in tobacco control legislation and in driving down the illicit market over the last decade.

The tobacco industry would be wise to focus more time on controlling its supply channels – which are fuelling the illicit trade – and less time on over-supplying media channels with myths intended to discourage measures that will reduce smoking rates, and in doing so, save lives.

The UK should sign and ratify the Protocol to Eliminate Illicit Trade in Tobacco Products at the next opportunity. It aims at eliminating all forms of illicit trade in tobacco products by requiring Parties to take measures to control the supply chain of tobacco products effectively and to co-operate internationally on a wide range of related matters.

Electronic cigarettes are to be regulated as medicines

It’s been an interesting few days for smokers intent on stopping their habit.

Last week saw welcome new guidance from the National Institute for Health and Care Excellence (NICE) – the first to recommend that licensed nicotine-containing products (NCPs) can be used to help people cut down on the amount they smoke (as well as to help them stop entirely).

Today the Medicines and Healthcare Products Regulatory Agency (MHRA) has made its long-awaited announcement of its intention to license NCPs such as e-cigarettes, which have – until now – fallen outside both medical regulation and NICE’s guidance for quitting and cutting down.

This is good news. We’ve wanted to see e-cigarettes come under “light touch” regulation for some time – as it could ensure their safety, quality and effectiveness, restrict marketing that risks cross-promoting tobacco smoking, and stop them being sold to under-18s.

So we think it’s a great idea to bring e-cigarettes within MHRA licensing.

The ideal solution?

One thing everyone interested in reducing the toll of tobacco can agree on is that e-cigarettes are a controversial issue. Our recent blog article on the topic covered some of the unanswered questions about e-cigarettes, and generated a lively discussion in the comments section.

In the article, we raised issues about the contents of e-cigarettes, their safety and their long-term use.

But it’s important to get the balance right: it would be wrong to give the impression that there are no risks at all – hence the call for light-touch regulation and monitoring. Yet it’s important to remember that using these products is almost certainly safer by far than smoking tobacco.

In the debate about e-cigarettes it’s not the product safety that’s most hotly disputed, but their potential impact on a smoker’s motivation to quit, and on the progress made so far in reducing the UK’s smoking rates.

Tobacco is by far the most important preventable cause of cancer in the world. Smoking accounts for one in four UK cancer deaths, and nearly a fifth of all cancer cases – including those caused by exposure to second-hand smoke.

The good news is that quitting smoking significantly reduces the chances of developing one of the fourteen cancers related to tobacco use. The sooner you quit the better, but it’s never too late. But nicotine is highly addictive and many attempts to quit smoking fail.

Some argue that e-cigarettes are a huge opportunity to wean smokers off a deadly product by offering a nicotine “hit” without them having to inhale tobacco smoke.

The argument goes that, in a free market, consumers will always choose a safer product over a more dangerous one – so the better e-cigarettes can replicate cigarettes, the more they will spur a mass move away from tobacco smoking with little need for further public health interventions.

This is after all what we all want – an end to the death and disease caused by smoking.

Fatal attraction

But as well as this promise, e-cigarettes have several potential theoretical downsides:

• what makes e-cigarettes beautiful could also make them dangerous – their replication of the act of smoking could be too close to the ‘real thing’ to allow smokers to ever effectively escape their tobacco habits and potentially to revert back to smoking tobacco;
• using e-cigarettes in smoke-free areas could potentially give smokers less motivation to quit smoking the rest of the time;
• and their use in smoke-free places and in marketing images could have a knock on effect of ‘renormalising’ smoking, by confusing or contradicting the messages about the harms of smoking. This could undermine public health efforts to deter young people from taking up smoking.

At this stage we simply don’t have the necessary evidence to be able to say with any confidence which of these arguments – if any – is correct. But we have plenty of experience to warrant some caution.

A market flaw?

Sitting above these opportunities and risks is something we’re extremely wary of: the fact that the big tobacco companies are investing in NCPs.

For example Nicoventures – the company that owns one of the first of these types of products to be put forward for MHRA licensing – is owned by British American Tobacco, one of the four companies that control over 90 per cent of all global tobacco sales.

In a future post, we’ll be exploring the issues of conflicting interests that arise from this dual corporate ownership of cigarettes and their potential nemesis.

But for now, we’re remaining mindful of the first principles of internationally agreed public health guidelines: “there is a fundamental and irreconcilable conflict of interest between the tobacco industry’s interests and public health policy interest”.

Watch this space.

Alison Cox, Tobacco Control Lead

The latest cancer news

Several important stories came out of the ASCO conference in Chicago this week:

• Taking tamoxifen for 10 rather than five years halves the risk of women dying from the most common kind of breast cancer, according to our clinical trial. The Daily Mail covered the story, and our press release has more detail.

• A low-cost vinegar-based screening test cut cervical cancer rates among Indian women by nearly a third. The Telegraph and Forbes both have more info.

• On the treatment front for cervical cancer, a drug called bevacizumab was shown to prolong survival in women with advanced disease. Medscape has more detail.

• There was a lot of buzz at the conference about a new class of cancer drugs called PD-1 inhibitors, which ‘unmask’ tumours that are invisible to the immune system. We wrote about these drugs’ early promise at last year’s conference, and it seems excitement is continuing to build. Here are our picks of the coverage: New Scientist, the New York Times, and NHS Choices.

• And finally on the ASCO front, our nurses team wrote from Chicago about personalised medicine, clinical trials for the elderly, and helping cancer patients to stop smoking.

There were plenty of other stories outside the conference walls:

• Rather unexpectedly, Michael Douglas triggered a lot of coverage about the link between oral sex and throat cancer. This Independent piece is our pick of the print coverage, and our expert was interviewed on the Today programme. This Guardian Q&A is also great.

• Anxiety is a greater risk than depression for long-term cancer survivors, according to research published this week. Read our news story for more info.

• NICE issued landmark guidance recommending that licensed nicotine-containing products can be used to help people cut down on the amount they smoke. Here’s our news story.

• Our scientists have found a molecular ‘bullseye’ for a rare form of melanoma, opening up opportunities for new targeted treatment. Here’s our press release.
• New figures released by Macmillan hit the headlines (here’s the BBC’s take), showing that nearly half of us will be diagnosed with cancer at some point in our lives. The good news is that rates are increasing because we’re living longer, and survival rates have been on the up too.

• But in a reminder that cancer’s been with us since prehistoric times, research in PLOS ONE showed that Neanderthals got tumours too, as reported here by the BBC.

• Cancer rates in Japan aren’t expected to rise in the aftermath of the Fukushima nuclear incident, according to a new UN report.

And finally

• We joined leading medical and research centres around the world this week to launch an ambitious project that will allow the sharing of vast amounts of genetic and clinical information. The Guardian and Nature have more detail about this exciting endeavour.

The Institute, based in London, is named after Professor Francis Crick – the Nobel Prize-winning scientist who, with Professor James Watson, discovered the double helix structure of DNA.

Yesterday, in the presence of Crick’s daughter, the Chancellor George Osborne, Minister for Universities and Science David Willets, and the Health Minister Earl Howe, a big step was taken towards making this a reality – the ‘topping out ceremony’ – celebrating the completion of the highest point of the new structure.

In glorious sunshine, we heard from the Institute’s first director Professor Sir Paul Nurse – himself a Nobel Prize winner and former CEO of Cancer Research UK. Professor Nurse laid out his vision for the institute as a “powerhouse and beacon of science in UK science whose doors will always be open for scientists to share their ideas and liberate their creative energies.”

This milestone coincides with the publication of the Strategic Plan [pdf], which sets out just how unique and groundbreaking the Institute will be when it opens in 2015.

The Plan outlines how the Institute will bring the very best minds from across the biological, clinical and physical sciences to address some of the most pressing issues that we face, from treating cancers and circulatory diseases to infectious diseases that devastate so many lives.

To do this, the Institute will not be afraid to do things differently – our chief executive Dr Harpal Kumar calls it a “game-changer for medical research”.

So what’s so different about the Crick, and why?

Colliding worlds

One of the Institute’s great strengths will be to bring together researchers from different backgrounds, with ‘fresh sets of eyes’ to provide new clues in the hunt for cures and treatments. It’s an approach embedded in the building’s background: Francis Crick was a physicist and James Watson was a zoologist. It is arguably their different approaches – working together – that were the key to their fundamental breakthrough in the 1950s.

Today, as research reveals more about how different diseases affect our bodies, it’s also showing how they overlap, demonstrating how discoveries in one area could open new avenues for treatments in others.

For example, our researchers’ expertise in brain tumour biology will be set alongside the knowledge of those working on brain development, and on other brain and central nervous system disorders such as Alzheimer’s and Parkinson’s diseases. This mutual proximity will boost their collective efforts, spark new ideas and – almost inevitably – lead to new treatments.

The next generation

In a departure from the usual career structure for scientists in the UK, the Crick Institute will act as an incubator for the best young scientists in the world. Focusing on researchers in the fledgling stages of their careers – when they’re at their most creative and uninhibited – the Crick will nurture their talents for up to 12 years before releasing them to other research institutes in the UK and beyond.

To support these young researchers during what can be a very vulnerable time in their careers, an ‘old guard’ of senior scientists will be given the job of mentoring and guiding them.

Opening new windows into the body

So what will they be looking at? To guide the work of the Institute the research strategy is based on seven broad questions:

• How does a living organism acquire form and function?
• How do organisms maintain health and balance throughout life and as they age?
• How can we use biological knowledge to better understand, diagnose and treat human disease?
• How does cancer start, spread and respond to therapy?
• How does the immune system know whether, when and how to react?
• How do microbes and pathogens function and interact with their hosts?
• How does the nervous system detect, store and respond to information?

These questions will provide the starting point for the melting pot of ideas that we hope will take our researchers closer to understanding more about cancer and new ways of treating the disease.

Making it happen

And to finish off this round of milestones, we’re delighted to announce that we’ve raised £34 million for the Francis Crick Institute, taking us more than a third of the way to our target of raising £100 million through the Create the Change campaign.

Donations so far have come from a range of major philanthropists and trusts, including an incredible £3 million gift from The Wolfson Foundation.

With all these milestones being reached it promises to be an exciting couple of years as we build up to the opening of the Francis Crick Institute in 2015.

Personalised medicine has been a hot topic for several years

In our third instalment from the ASCO cancer conference, Debbie Coates writes about a major theme of modern cancer research – the concept of personalised medicine.

It’s an exciting time in the world of cancer treatment. We know more than ever before about the genetic faults driving different cancers, and we’re getting better at designing drugs that target them.

At the same time, it’s becoming clear that the more we know, the more complicated things become. As we start using genetics to classify tumours, we find that the number of cancer types is growing rapidly – for example, only last year our scientists in Cambridge showed that breast cancer is actually at least ten different diseases.

There are also huge challenges with developing drugs targeting these changes – not least designing the clinical trials to test them.

Several sessions at this year’s ASCO conference discussed the issues being thrown up by our progress into the era of personalised medicine.

A key problem is that the genes faults differ from one cancer type to another – the ones we commonly see in breast cancer aren’t always the ones we see in lung or bowel cancer, for example. And when we do occasionally see faults that are common in many different cancers, we don’t yet have the drugs to target them.

Another problem is that, in a single type of cancer, there may be a very small numbers of patients with a particular mutation. This means researchers will need to adapt the way they design trials to show whether a drug works for people who have that particular mutation.

We also have to face up to the idea that different groups of cells within a tumour have different genetic faults – an issue known as ‘intratumour heterogeneity’. This suggests that doctors will need to figure out what’s going on in different parts of the tumour (for example by taking multiple biopsies, or working out how to analyse DNA in the bloodstream).

And it also implies that not all cells within a cancer can be targeted by a single drug. So using combinations of targeted drugs – or using them in particular sequences – may be needed.

The repertoire of gene faults within a tumour may also change over time, so several speakers suggested that doctors cannot just rely on initial biopsies when planning treatments – they’ll probably need to keep monitoring things over time to find out whether the genetic make-up has changed.

But some of the gene changes may make the cancer resistant to particular drugs, and treatments themselves can sometimes cause genetic changes. We’re learning more and more about this and our very own Professor Charles Swanton gave an excellent talk about the research his team is doing into this important area.

With so many different genetic changes and emerging targeted treatments, it can be difficult for doctors to match their patient to the drug most likely to work for them. In response to this, ASCO has developed a data bank called CancerLINQ, which is collecting data about patients, treatments and the effectiveness of treatments.

Doctors can share their data and so speed up the rate at which we can identify the most effective targeted treatments and find out the best ways of using them.

Finally, Dr David Solit of the Memorial Sloan Kettering Cancer Centre, New York talked about his work looking at secondary tumours (aka tumour spread or metastases). He highlighted that secondary tumours can differ from each other as well as from the primary tumour – and that tumour heterogeneity can also exist in a secondary tumour.

This helps us understand why some areas of metastasis may shrink in response to a particular treatment but other areas of metastasis may continue to grow. This again has implications for future treatment.

Dr Solit also described how cells from a secondary tumour can break away, circulate in the blood and reach the primary tumour – delivering cells with new genetic changes – a phenomenon he referred to as ‘self-seeding of the primary’. All in all, keeping up with how primary and secondary tumours change over time will pose quite a challenge.

It would be easy to feel disheartened by all these challenges. But in between and after presentations, you can see scientists and doctors gathering to debate, brainstorm and forge new collaborations – energised and undaunted by the sheer scale of the task they face. The clear message from this year’s ASCO is that we are up for the fight.

Debbie Coats, Clinical Information Manager 

Clinical trials are vital for improving treatment for people with cancer

In our second report from this year’s ASCO conference, Trevor Bott writes about a session he attended on the need for clinical trials for older cancer patients.

People are living longer thanks to improved living standards and phenomenal medical progress in recent decades. That’s the good news.

But our aging population comes at a price: the biggest risk factor for cancer is old age, so the flipside is that the number of people developing cancer is set to soar.

Estimates vary, but an older population definitely means many more elderly men and women with cancer in future – one speaker said that by 2030 the incidence of cancer in the US will rise to 67 per cent in the over 65s compared with just 11 per cent in the under 65s.

That’s why ASCO put on a session about clinical trials for older patients. Such trials – which form the backbone of medical progress – are crucial if we’re to find the best way to treat the increasing number of older people with cancer.

Yet doctors don’t routinely ask older patients if they want to be enrolled on a clinical trial, because they are wary of the potential side effects of the drugs. They’re also concerned about how the treatment might affect other medical conditions that elderly patients may have.

In the 21st century, age is not necessarily a good indicator of fitness, and older people should not be denied the best treatment simply because of their age.

The overriding sentiment of this fascinating session was that we need to move away from an outmoded culture of broad-brush rejection of clinical trials for older patients, and to an era where we better understand the special considerations required for elderly patients on trials.

Many clinical trials exclude people over a certain age, or with concurrent medical conditions. This means that we know less about how cancers behave in older people and less about how well treatments may work. If we designed more trials specifically for older people we could look at things like:

• How cancers behave differently in the elderly;
• Designing trial end points specifically for older patients (so rather than measuring how long it takes for disease to progress for instance, use more appropriate end points such as ‘TWiST’ – Time Without Symptoms or Toxicity);
• Using functional age instead of chronological age (that is, ‘how fit’ the person is, rather than ‘how old’);
• Different ways of treating cancers, such as starting with lower doses of medication and slowly increasing;
• Enrolling older patients in smaller ‘sub-trials’ within bigger trials, so that considerations like those above could be included in the trial design.

Finally, we heard that given the chance, many elderly patients would take part in a clinical trial. In a survey, 75 per cent of patients over 70 said they would be willing to take part.

Increasingly, trials are being designed specifically for older people, such as the HCQ trial, supported by Cancer Research UK.

But the message from doctors and patients is loud and clear. We need more clinical trials designed to meet the needs of the majority of our patients – older men and women.

Trevor Bott, Clinical Trials Database Nurse

Advances in imaging techniques are helping to analyse childhood brain tumours

Despite the huge progress that’s been made in treating many types of childhood cancer, brain tumours are lagging behind. Although these diseases are relatively rare – and the chances of surviving have increased over the past few decades – brain and spinal cord tumours are the leading cause of cancer death in children, claiming more than one hundred young lives every year.

One of the major challenges in treating these tumours in children is working out what’s going on deep inside their growing brains. There are many different types of brain tumour, each requiring different treatment approaches and with varying chances of survival. But despite advances in imaging, such as MRI scanning, that help doctors see inside the ‘black box’ of the skull, it’s still hard to figure out exactly what sort of tumour a child has without resorting to invasive surgery.

In two related papers, published earlier this year in the European Journal of Cancer, Professor Andrew Peet and his team at the University of Birmingham have taken a step forward in developing a non-invasive technique that could help doctors to diagnose childhood brain tumours more accurately before surgery, as well as helping them choose the best way to treat them. And Cancer Research UK’s support, through our Imaging Programme, was essential for making it happen.

Let’s take a closer look at what they found.

What’s the problem?

Childhood brain tumours are a complex and diverse group of more than a dozen diseases affecting different tissues in the brain in various ways. And while an MRI scan can provide a lot of information about where a tumour is lurking, it often can’t help doctors pin down the exact type, nor how aggressive it might be.

The next step towards getting a definitive diagnosis is usually surgery to remove the tumour, which can then be analysed by a pathologist to give a more detailed answer. But in many cases, it would be incredibly helpful to have more information about the tumour before heading into the operating theatre. This would enable doctors to plan the best possible approach and decide whether other treatments, such as chemotherapy, are likely to be needed too.

And there are also implications for the extent of the surgery itself. For example, some types of brain tumour need to be completely removed to give the best chances of surviving, while in other cases it’s OK to leave a small amount of tumour as long as it’s mopped up later with chemotherapy and radiotherapy. The more tumour a surgeon has to remove, the greater the chances that healthy brain tissue will end up getting damaged. But it’s hard to know how far to cut if accurate information about the type of cancer is only available in hindsight, once the pathology reports come back from the lab days later.

There have been some recent advances to help surgeons make these kinds of decisions in the operating theatre, such as making tumours ‘glow-in-the-dark’, but knowing more in advance would be a huge help.

Wobbling molecules to analyse tumours

To try and shine light inside this black box, Professor Peet and his team are using a technique called Magnetic Resonance Spectroscopy (MRS), which allows them to analyse the levels of certain molecules inside tumours. It relies on the fact that molecules ‘wobble’ in particular ways when they’re in a strong magnetic field. This wobbliness is measured and analysed using complex computer programmes, building up a characteristic ‘fingerprint’ called a spectrum, which looks a bit like the ridges and valleys of a mountain range:

A typical MRS spectrum from a brain tumour, taken from Peet et al (2012) Nature Reviews Clinical Oncology

Researchers have already used this technique to analyse brain tumours in adults, but it isn’t usually used in children’s cancers, which are quite different from those in grown-ups.

Because childhood brain tumours are rare, the researchers had to work together with doctors in 10 treatment centres in Europe and South America to gather enough suitable patients. In total, they managed to analyse 97 children with a range of different types of cancer, including 11 with ependymoma, 29 with medulloblastoma, and 38 with pilocytic astrocytoma, as well as a handful of children with other less common tumour types.

The scientists found that each of these three major tumour types had a distinctive spectrum, which could be easily identified. What’s more, the fingerprints of tumours in a particular part of the brain known as the posterior fossa looked slightly different from those growing elsewhere.

But it’s not just in diagnosing the particular type of tumour in a child where this technique could be useful. Patients who appear to have the same type of cancer can respond very differently to the same treatment. However, at the moment it’s difficult for doctors to predict which children are likely to do better and benefit from milder treatment, and which might do worse, needing a more intensive approach.

Professor Peet and his team in Birmingham

Studying 115 children who had come to Birmingham Children’s Hospital with a brain tumour, Professor Peet and his team found that their MRS technique can also be used to predict how individual patients would fare after treatment. They discovered that children whose tumours have certain chemical fingerprints had a relatively good outlook, while those with different signatures were likely to do worse – in particular those whose tumours contain lots of fatty molecules.

What next?

These results tell us that MRS is promising as a non-invasive way of analysing childhood brain tumours, providing information that could help surgeons and doctors make better decisions about how best to treat their patients. And the team’s work also reveals more about the molecular changes that are happening deep within brain tumours, helping to explain how they develop and grow.

This is the largest study ever undertaken using MRS for analysing childhood brain tumours. And although there still needs to be a bit of tweaking on the technical side of things, there’s a good argument for incorporating the technique in further large international clinical trials to bring benefits to more children in the future.

MRS is available already in many major hospitals and can be used in addition to MRI scanning in helping to diagnose and treat children with brain tumours. However, the sophisticated analysis developed by Professor Peet and his team is not yet ready to be used routinely in the clinic, so it won’t change how patients are diagnosed and treated right now.

Childhood brain tumours are still a huge challenge for doctors and scientists, but research is our best way of beating them. Cancer Research UK funding played a vital role in this project, through our Imaging Programme in Birmingham.

In turn, that funding simply wouldn’t be there without the generosity of our supporters who –  like us – want to see the day when no child loses their life to cancer.  We’ve got a long way to go, but every step takes us in the right direction.

Kat

References:
Wilson M. Et al (2013). Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours, European Journal of Cancer, 49 (2) 457-464. DOI: 10.1016/j.ejca.2012.09.002

Vicente J. et al (2013). Accurate classification of childhood brain tumours by in vivo 1H MRS – A multi-centre study, European Journal of Cancer, 49 (3) 658-667. DOI: 10.1016/j.ejca.2012.09.003