A Refresher from the BBC

Regular readers will probably feel they know all this stuff but if you’re interested in a spirited and wide-ranging conversation about cancer with the wonderful Jeremy Vine on his BBC Radio 2 show yesterday you can find it at:

http://www.bbc.co.uk/programmes/b03yn0jd about 1 hour 10 min from the beginning.

BBC Radio 4As ever, any arising thoughts, questions or comments appreciated – apart, of course, from the below the belt: “Judging by the photo it’s a good job it was radio not t.v.”

 

Isn’t Science Wonderful? Obesity Talks to Cancer

A couple of week’s ago we looked at how being obese can give cancer a helping hand. I thought this would be useful as most people know there is a link but perhaps not much more than that. The message had two simple parts: (1) When we make extra fat cells they change the metabolism of our bodies through chemical signals that wander around and, in passing, can also drive cancer growth, and (2) Some of the extra fat cells congregate around tumours and give them direct positive vibes (i.e. other, local chemical signals).

But you may have spotted that I didn’t actually say what these ‘signals’ are – for the very good reason that we know rather little about them. Step forward, right on cue, Ines Barone, Suzanne Fuqua and friends from the University of Calabria and Baylor College of Medicine, Houston with a wonderful paper that’s just been published. Wonderful because it’s got so much data I’m green with envy but also because, like most excellent science papers, the key message is simple: normal cells that have moved into the neighbourhood can indeed talk directly to tumour cells. And the messenger is … leptin!

That’s astonishing. Even those with only a smattering of knowledge about how we work will know that leptin plays a key role in regulating energy balance. It’s a protein – a hormone – that circulates in our blood at levels roughly proportional to body fat. Its job is to signal the ‘full’ state, i.e. to reduce appetite. Somewhat perversely, obesity usually causes abnormally high leptin levels but it doesn’t work very well because the body has become resistant to its signal – much as happens with insulin in type 2 diabetes.

The new results show that leptin, released from nearby cells, can bind to cancer cells and make them do two things: (1) Release a chemical that tells the adjacent cells to send out even more leptin, and (2) Make proteins that help the tumour cells grow and invade.

There are a few wrinkles to these results. The study was on breast cancer cells with a particular mutation (in a receptor for the hormone estrogen) and the ‘groupies’ providing the leptin turned out not to be fat cells but fibroblasts – part of the supportive framework of cells and tissues – so they’re ‘cancer-associated fibroblasts’ (CAFs). And when the CAFs release leptin it floods out and the tumour cells embrace it and make yet more receptors for leptin to bind to on their surface.

But these details matter less than the key point: for at least some types of cancer cell a hormone often made in excessive amounts in obesity can signal directly to tumour cells, telling them to grow and spread. This doesn’t mean that all breast tumours, yet alone all cancers, respond to leptin. What it does show is that a key factor in obesity can talk directly to some types of tumour cell. It’s another example of the painstaking way in which science usually proceeds and, assuming the results are reproducible, we have one more little bit of the jig-saw.

Reference

Barone, I., Catalano, S., Gelsomino, L. et al. (2012). Leptin Mediates Tumor−Stromal Interactions That Promote the Invasive Growth of Breast Cancer Cells. Cancer Research 72, 1416-1427. 

Biting the bitter bullet

The other day we took a short trip around obesity (Obesity and Cancer) in the course of which we noted that the former is a bad thing. So, you might say, they make a good pair – indeed they quite often come hand-in-hand, as obesity significantly increases the risk of quite a lot of cancers as well as other unpleasant conditions. The nasty effects include heart diseases and diabetes, a collection of problems often referred to as metabolic syndrome.

Fed up?

Obesity is usually caused by eating too much of the wrong stuff whilst parked on your rear end. True enough, but folk sometimes get a bit cheesed off by repeatedly being told to do something about it. As it happens, turning to Cheddar, if you can face the stuff, may actually help weight loss as cheese is high in protein and fills you up. And you might just go for that escape route when you’ve been leaned on by a recent article that, in effect, calls for draconian measures to limit the amount of sugar we eat. To be slightly more precise, the target is the USA because, as is well known, Americans lead the world in pretty well everything, including bad eating habits. The scientific dynamite propelling the charge is that sugar consumption worldwide has gone up three-fold in the last 50 years. The average American now eats over 600 grams of the stuff every day, a feat that leaves the rest of the world scarcely within range of a podium spot. It may seem a bit odd to be left trailing at anything by the most obese nation in the world (let’s leave Nauru –pop. 9265 – and a few other South Sea islands out of it)  but the link here is, of course, that sugar is a great source of calories and that the more calories you shovel down – in whatever form – the bigger you tend to become. But don’t get too cheeky about Yankee obesity as us Brits aren’t in great shape either.

Condensed facts

Very roughly an ‘average’ person needs about 2,100 calories a day. 600 grams of sugar would give between one third and one quarter of that total requirement. For an historical perspective that’s about 14 times as much sugar as the denizens of Great Britain were allowed during the second world war under rationing – a period when our diet is generally considered to have made us healthier than we’ve ever been. So you could say an element of control has been lost.

Calorific confusion

The ‘2,100 calories’ above are ‘food calories’, the unit sometimes used in nutritional contexts. It’s 1000 times bigger than ‘scientific’ calories, or gram calories (cal). Scientifically therefore, we mean 2,100 kilocalories (kcal). Which is why your fruit juice carton may tell you one glass contains 50 kcal. And, just to stop you asking, 1 calorie is the heat (energy) you need to raise the temperature of 1 gram of water from 14.5oC to 15.5oC.

An all-round view of the problem

Sugar consumption has ski-rocketed, eating too much of it unbalances your diet and bad eating habits can cause obesity and metabolic syndrome. But these things aren’t black and white: 20% of obese people have normal metabolism and a normal lifespan whilst 40% of those of normal weight will get metabolic syndrome diseases. So, whilst obesity indicates metabolic abnormality, it is not per se the cause.

The underlying science remains a matter of debate – a story well summarized by Gary Taubes. What is not in question is that we eat more sugar than we need and the real crunch is that sugar is like tobacco and alcohol – no, it doesn’t make you smelly or do Sinatra impressions – but it is addictive. It actually manipulates your pathetic brain cells so you keep asking for more.

On your Marx

So we’re seduced into eating more and more of something that can help us get fat and ill. What’s to be done? Lenin, who was fond of asking this question, would have dealt with it in a trice by limiting sugar supplies to one tenth of the dietary minimum and seeing who survived. Ah! The good old days. But the authors of the recent article had to come up with a pc 21st century equivalent. Of course! Taxation. And they’ve a point – you can tell people that smoking will give them lung cancer til you’re blue in the face but the only thing that stops them committing suicide is jacking the price up. Don’t ask me. Something to do with human nature. So it sounds like a good idea – but to have an effect on sugar you’d need a huge increase across a vast range of foods – fruit juice, ‘sports’ drinks, chocolates, sweets, cakes – forget it.

Do I have a solution? Of course! Bring back rationing. For all foods. Set at the UK second world war levels. Now we’d think about what we eat – carbohydrate, protein and fat – reverse obesity trends, solve world food problem, slash health service costs, cut queues at supermarkets (so they’d be normarkets). And we’d be rid of most of those damned cheffy t.v. programmes. Vote for me!!

Reference

Lustig, R.H., Schmidt, L.A. and Brindis, C.D. (2012). The toxic truth about sugar. Nature 482, 27-29.

Gary Taubes (2011). Is Sugar Toxic? The New York Times.

Rasher Than I Thought?

A recent report concluding that if you eat processed meat (bacon, sausages and suchlike) you’re more likely to get cancer in your pancreas has attracted predictably wide media coverage. More surprisingly, the reports I noticed (BBC News, Sky News and Guardian) were fairly reasonable accounts, quoting the main figures, the source of the information (British Journal of Cancer) and one or two ‘expert’ comments thereon. Usually science reporting in the ‘media’ is more feel than fact and appears to be motivated by coming up with eye-catching headlines rather than precise explanations (being precise, there is a Bacon Eaters Warned Of Deadly Cancer Risk in the above – but let’s not be too critical).

What the papers didn’t say

What such reports almost always fail to mention – and these were no exception – is how devilishly difficult it is to do surveys linking what we eat to what happens to our bodies. One method is to get a group of people with a given disease and ask them what they’ve eaten over the last umpty months/years/decades. You don’t need to be a stats wizard to see the major problem with this! Alternatively, so-called ‘prospective studies’ start with healthy individuals who are followed for exposure to potential factors and subsequent development of disease. Exposed and unexposed sub-groups are compared for disease rates. There are huge problems with these studies too, not the least being that you have no real idea how well the punters stick to the rules – in this case, what they eat.

The predictable upshot over many years has been that, apart from fruit and veg (good anti-cancer stuff, as we all know), for pretty well every survey showing something we eat gives us cancer there’s another that says it either has no effect or it’s actually protective.

Much easier than actually doing either type of survey is to do what these processed meaters did: put together all the sensible studies you can find (in this case eleven prospective surveys between 1966 and 2011) and see if a clear message emerges. Though not perhaps evident at first sight, this is actually quite a useful thing to do because by lumping all the data together you get a large number of patients and controls and the hope is that, out of the confusion of multiple smaller surveys, clarity will come forth.

And, up to a point, it did. The relative risk of pancreatic cancer emerged as 1.19 if you eat 50 g of processed meat every day (it would be 1.00 if you take The World Cancer Research Fund’s advice and avoid the stuff altogether). And, of course, the risk goes up the more of it you eat.

How scary is that?

So where does that leave us and how scared should we be by the scary headline? Have I been unwittingly irresponsible indulging a life-long taste for bacon, sausages and such like? Mmm…bacon…Mmm…sausages. (Sorry – Homeric moment there). Well, something like a 20% risk increase may be significant but it isn’t huge. Then 50 g is a fair wodge of bacon or whatever to eat every day. What’s more, the authors admitted that they’d had to make a few assumptions about just how much processed meat people actually had eaten in the various studies they collated, because some only listed ‘servings’ or ‘times’. Then there’s the question of how is the deed done if processed meat does drive cancer? The study authors noted that the most likely culprit is preservatives commonly added to such food – because these can indirectly cause DNA mutations. Having just salivated round the wondrous display of meats, hams, bacons, sausages etc. in my local Farm Shop (Gog Magog Hills: don’t miss it if you’re anywhere near Cambridge) I note than none of their stuff contains additives or preservatives. Whew!!

And the bottom line…

So my advice to me is: don’t panic, don’t pig out – but do keep an eye on where piggy bits come from. All of which is not to minimise the threat of pancreatic cancer. It’s the eighth biggest cancer killer worldwide, nearly 8,000 Brits died from it in 2008 and there’s no effective treatment. What’s the best thing to do – or not to do? Well, as we’ve said, take it easy on the bacon butties. But two things are strongly associated with pancreatic cancer: smoking (contributes to 20% of cases) and obesity. Not smoking’s easy, of course. Now, how to avoid getting fat…

Reference

Larsson, S.C. and Wolk, A. (2012). Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies. British Journal of Cancer advance online publication 12 January 2012; doi: 10.1038/bjc.2011.585.

Are You Ready To Order?

Next time you’re grappling with menu selection you might wish to thumb through the latest bit of government advice on what to eat. It comes from The Scientific Advisory Committee on Nutrition (SACN) and, as it runs to 374 pages, you’re unlikely to have missed it. They’re trying to stop you getting bowel cancer and their advice is don’t eat more than 70 grams a week of red or processed meat. Processing meat means smoking, adding salt or otherwise curing to limit decay. There’s a lot of meat in this report: it tells you not only how much iron you get from different types of food but, perhaps more helpfully, what 70 grams looks like (it’s a lamb chop or two slices of beef). So, as a fact file it’s well worth the price (you can download from the web).

What’s the problem?

There are three potential sources of trouble in these foods. The first is that redness in meat comes from blood, specifically the iron-containing haem group in red blood cells that carries oxygen. When haem is broken down in our gut one product is a chemical group called nitroso compounds (that’s a nitrogen and oxygen atom (–N=O) that can attach to other groups to make a family). The second is that meat’s better eaten cooked than raw and cooking at high temperatures produces substances that can pass from the stomach to the circulation. There’s one report that shows how often you flip your burgers on the grill may affect this factor! The third problem is that suppliers often add chemicals to meats to give colour and flavour and to stop bugs growing.

What do these have in common?

Each of these trouble sources involve chemicals that can damage DNA – that is, either directly or after conversion to something else, they can cause mutations and thus help to promote cancer. The evidence that they can do this in rats is clear but it comes with the rider that, generally, far higher doses than humans would ever consume are required or they cooperate with other tumour-causing chemicals to make them more effective – the rats will get tumours from one treatment: the meat-related chemicals just make them grow faster.

So much for rats, what about humans?

Over the years a number of large and seemingly well-conducted studies have shown that you’re more likely to get bowel and stomach cancers if you eat lots of red or processed meat. The risk is not huge: the most recent review of the major studies concludes that the relative risk is 1.18 for those with a high haem iron intake – which the authors describe as ‘modest’. Remember that’s an 18% risk increase: a relative risk of 2.0 means your risk is doubled.

It should be added that the various bodies responsible for meat production have been quick to point out that there are also large and seemingly well-conducted studies showing no link between meat eating and cancers.

A masterpiece!

So this report is another look at a long-running controversy over a non-trivial matter, given that cancer of the colon or rectum is, world-wide, the third most common form. What it neither does nor pretends to do is tell us anything new. It simply reviews the data and presents its conclusions in a brilliantly detached, scientific assessment. It notes that green vegetables and potatoes are a much greater source than preserved meats of the chemicals used as meat additives and concludes that the data do not support a link between them and bowel cancer. On a link between iron-rich diets and bowel cancer in humans, it points out that The World Cancer Research Fund considers the evidence to be  ‘sparse, of poor quality and inconsistent’ and that it is not possible to quantify the association. Its delicate conclusion is that ‘It may be advisable for adults with relatively high intakes of red and processed meat (over 90 grams/day) to consider reducing their intakes.

Having digested all this, the next time the waiter appears at your elbow, don’t panic! Recall that mankind evolved eating meat because it’s a mighty good source of protein, vitamins and minerals. If the roast beef smells good, crack on and enjoy it!! Yes, it might add fractionally to your risk of getting bowel cancer in years to come. But when you finally stagger out of the restaurant (full but not satiated) remember that crossing the road will contribute fractionally to your risk of being squashed by a truck. Just do everything with your eyes open and don’t over-do anything!

References

Scientific Advisory Committee on Nutrition (SACN) Iron and Health Report – 25th February 2011.

Bastide, N.M., Pierre, F.H.F. and Corpet, D.E. (2011). Heme Iron from Meat and Risk of Colorectal Cancer: A Meta-analysis and a Review of the Mechanisms Involved. Cancer Prevention Research 4, 177-184.

http://www.abovetopsecret.com/forum/thread449442/pg1

Third-hand smoke

Most people who read this will know that the major cancer world-wide is lung cancer (both new cases and deaths), most of which (about 90%) are due to tobacco use. Anti-smoking publicity has been effective in parts of the developed world, and it’s drawn attention to the risks of ‘second-hand’ or ‘passive’ smoking – known since the 1930s – with the result that, at last, smoking is now banned in many public places.  This has contributed to the decline in the number of men dying from lung cancer in both the USA and the UK since 1980. It’s also helped to stabilise over the last 10 years the lung cancer death rate of American women although, as ever, the Brits are lagging behind and the rate for British women is still rising.

An additional facet of this problem has recently begun to be recognized in the form of ‘third-hand smoke’ – meaning that residual contamination may be present long after someone has smoked in the area. Inevitably, Sod’s Law appears to apply in that the chemicals that hang around by sticking to surfaces include some of the more toxic of the 1000 or so in cigarette smoke. No non-smoker who has tried snuggling up to a smoker or merely been ushered into a hotel room previously occupied by one will need convincing of the reality of  ‘third-hand smoke’. However, a recent study from the University of Rochester Medical Center in New York has thrown an alarming light on the combined effects of second- and third-hand smoking by showing that children living in apartments suffered substantially greater exposure to tobacco smoke compared with those living in detached homes, even when no one smoked in their household. The conclusion came from measurement of the blood levels of a substance called cotinine, which is produced from nicotine and gives a quantitative estimate of exposure to tobacco smoke.

No study of this type is without its weaknesses – an obvious one in this case being that you can only go on what you are told about whether people smoke in their own homes. However, 5,002 children were studied, which is a reasonable number from which to make preliminary deductions, and the finding that those living in apartments had a 45% increase in cotinine over those living in detached houses is an arresting result.

It is clear that in explaining these results the distinction between ‘second’ and ‘third’-hand smoke becomes blurred but one factor would appear to be tobacco smoke disseminating through multi-unit apartments. Regardless of precise mechanisms, the authors leave us with the fact that most children in the US are exposed to tobacco smoke, including a proportion of those whose parents don’t smoke, despite the fact that we know the damage it can do. Recall that it is associated not only with the long-term risk of lung cancer but with a variety of illnesses of increasing incidence, particularly asthma, and that there is no such thing as a ‘safe level’ of exposure.

Reference

Wilson, K.M., Klein, J.D., Blumkin, A.K., Gottlieb, M. and Winickoff, J.P. (2011). Tobacco-Smoke Exposure in Children Who Live in Multiunit Housing. Pediatrics 127, 85-92.

http://www.quit-smoking-central.com/third-hand-smoke.html