Dennis’s Pet Menace

As it happened, I’d already agreed to appear on Jeremy Sallis’ Lunchtime Live Show on BBC Radio Cambridgeshire – the plan being just to chat about cancery topics that might be of interest to listeners. Which would have been fine – if only The World Health Organization had left us in peace. But of course they chose last Tuesday to publish their lengthy cogitations on the subject of whether meat is bad for us – i.e. causes cancer.

Cue Press extremism: prime example The Times, quite predictably – they really aren’t great on biomedical science – who chucked kerosene on the barbie with the headline ‘Processed meats blamed for thousands of cancer deaths a year’.

But – to precise facts – and strictly it’s The International Agency for Research on Cancer, the cancer agency of the World Health Organization (WHO), that has ‘evaluated the carcinogenicity of the consumption of red meat and processed meat.’

But hang on … haven’t we been here before?

Indeed we have. As long ago as January 2012 in these pages we commented on the evidence that processed meat can cause pancreatic cancer and in May of the same year we reviewed the cogitations of the Harvard School of Public Health’s 28 year study of 120,000 people that concluded eating red meat contributes to cardiovascular disease, cancer and diabetes. To be fair, that history partially reflects why the WHO Working Group of 22 experts from 10 countries have taken so long to go public: they reviewed no fewer than 800 epidemiological studies! However, as the most frequent target for study was colorectal (bowel) cancer, that was the focus of their report released on 26th October 2015.

So what are we talking about?

Red meat, which means any unprocessed mammalian muscle meat, e.g., beef, veal, pork, lamb, mutton, horse or goat meat, that we usually cook before eating.

Processed meat: any meat not eaten fresh that has been salted, cured, smoked or whatever and commonly treated with chemicals to enhance flavour and colour and to prevent the growth of bacteria.

What did they say?

Processed meat is now classified as carcinogenic to humans – that is it goes into the top group (Group 1) of agents that cause cancer.

Red meat is probably carcinogenic to humans (Group 2A). Group 2B is for things that are possibly carcinogenic to humans.

Why?

Because 12 of the 18 studies they reviewed showed a link between consumption of processed meat and bowel cancer and because it’s known that agents commonly added to processed meat (nitrates and nitrites) can, when we eat them, turn into chemicals that can directly damage DNA, i.e. cause mutations and hence promote cancers.

For red meat 7 out of 15 studies showed positive associations of high versus low consumption with bowel cancer and there is strong mechanistic evidence for a carcinogenic effect i.e. when meat is cooked genotoxic (i.e. DNA-damaging) chemicals can be generated. They put red meat in the probably group because several of the studies that the Working Group couldn’t fault – and therefore couldn’t leave out – showed no association.

Stop woffling

My laptop likes to turn ‘woffling’ into ‘wolfing’. Maybe it’s trying to tell me something.

But is The WHO trying to tell us something specific about wolfing? To be fair, they have a go by estimating that every 50 gram portion of processed meat (say a couple of slices of bacon) eaten daily increases the risk of bowel cancer by about 18%. For red meat the data ‘suggest’ that the risk of bowel cancer could increase by 17% for every 100 gram portion eaten daily.

And what might that mean?

In the UK about 6 people in 100 get bowel cancer: if you take The WHO maximum estimate and have everyone eat 50 grams of processed meat every day of their lives such that 18% more of them would get bowel cancer, the upshot would be 7 people in 100 rather than 6. So it’s a small rise in a relatively small risk.

As the report points out, the Global Burden of Disease Project reckons diets high in processed meat cause about 34,000 cancer deaths per year worldwide and, if the reported associations hold up, the figure for red meat would be 50,000. Compare those figures with smoking that increases the risk of lung cancer by 20-fold and The WHO’s estimate of up to 6 million cancer deaths per year globally caused by tobacco use and 600,000 per year by alcohol consumption.

All of which suggests that it isn’t very helpful to lump meat eating, tobacco and asbestos in the same cancer-causing category and that The WHO could do worse than come up with a new classification system.

And the message?

Unchanged. Remember mankind evolved into the most successful species on the planet as a meat eater. As the advert used to say: It looks good, it tastes good and by golly it does you good – not least as a source of protein, vitamins and other nutrients. Do some exercise and eat a balanced diet – just in case you’ve forgotten, that means limit the amount of red meat (The WHO suggests no more than 30 grams a day for men, 25 g for women) so try fish, poultry, etc. Stick with the ‘good carbs’ (vegetables, fruits, whole grains, etc.), cut out the ‘bad’ (sugar – see Biting the Bitter Bullet), eat fishy fats not saturated fats and, to end on a technical note, don’t pig out.

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‘The Divine Swine’ Castelnuovo Rangone, Italy

Meanwhile back on the Beeb

When the meat story broke I was a bit concerned that we might end up spending the whole of Lunchtime Live on how many bangers are lethal – especially as we were taking calls from listeners. Just in case things became a bit myopic I had Rasher up my sleeve. Rasher, you may recall, was Dennis the Menace‘s pet pig (in the The Beano‘s comic strip) who had a brother (Hamlet), a sister (Virginia Ham) and various other porky rellos. To bring it up to date we’d have introduced Sam Salami and Frank Furter and, of course, Rasher’s grandfather who was the model for the bronze statue named ‘The Divine Swine’ to be found in the little town of Castelnuovo Rangone in Pig Valley, Italy, the home of Parma ham.

But I shouldn’t have worried. All was well in the hands of Jeremy Sallis who, being a brilliant host, ensured that we mainly chatted about meatier matters than what to have for breakfast.

References

Press release: IARC Monographs evaluate consumption of red meat and processed meat.

Q&A on the carcinogenicity of the consumption of red meat and processed meat.

Carcinogenicity of consumption of red and processed meat. www.thelancet.com/oncology Published online October 26, 2015

Our Inner Self

Richard Gettner is the anti-hero of Christopher Fry’s wonderful play The Dark is Light Enough, set in the Austro-Hungarian war of 1848. Viewing himself as a failed author, failed husband and all-round disaster, he’s just absented himself from the Austrian Army on the basis of not being too nifty at soldiering either. Their minions are hot on his heels, intent on meting out the retribution that the military traditionally reserve for deserters, and he’s taken refuge in the family home of his former wife. In a tête á tête with her she rebukes him for his knack of self-destruction and points out that his book was actually quite well received and wasn’t really a failure. All Gettner’s frustration then bursts forth in a tirade of brutal philosphising:

‘Is there another

Word in the language so unnecessary

As ‘fail’ or ‘failure’?

No one has ever failed to fail in the end;

And for the very evident reason

That we’re made in no fit proportion

To the universal occasion; which, as all

Children, poets and myth-makers know,

Was made to be inhabited

By giants, fiends, and angels of such size

The whole volume of human generations

Could be cupped in their hands;

And very ludicrous it is to see us,

With no more than enough spirit to pray with,

If as much, swarming under gigantic

Stars and spaces.’

Fry deserves to be remembered as one of the great poetic wordsmiths of the English language, if only for The Dark is Light Enough but, had he known that nine out of ten cells in our bodies are bugs, he might have added a final blast to his demolition of the human condition:

Our failings should not surprise as we are but a sinister symbiosis,

More bacterial than human,

Helpfully poised such that when our hour is done

The microbial hordes surge forth to reduce us to our component parts.

bacteria and virus cartoon

The range of the hordes

Our rising preoccupation with the bug army (see it’s a small world & The Best Laid Plans In Mice and Men …) has been promoted by several recent studies that have propelled our ‘inner organism’ from the bowels of biology into the limelight. The story is somewhat fragmented but it’s a good time to see if we can make sense of the current threads.

We’ve known for many years that a motley collection of microorganisms are happy residents in most of our nooks and crannies, ranging from tummy buttons and through the skin, to saliva and our guts. They include bacteria and fungi, they’ve become known as the human microbiome (or microbiota), are said to outnumber human cells 10 to 1 and, all-told, can be viewed as a co-evolved ‘super-organism’ that has many benefits, including making our metabolism more efficient and hence improving nutrition. However, as with everything else in biology, this close relationship is a balancing act, the disturbance of which carries risks for disease development.

It’s critical to note that this vast microbial army, toiling away on our behalf in the dungeon of our innards, mostly dwelling in our gut, is a really mixed lot. It’s estimated to include about 700 different species of bacteria, of which perhaps thirty or forty species make up the bulk. It’s a bit like a mini Great Barrier Reef, well known as the world’s largest coral reef system and extraordinary in that, although it’s made up of billions of tiny organisms, the thing can behave in an integrated way, most dramatically illustrated by mass spawning.

Within the gut there are two major sub-families of microorganisms (Bacteroidetes (Bs) and Firmicutes (Fs)). Although more close-knit genetically speaking, each of these still includes many different classes of microbe. So, they’re a bit of a rabble but, by and large, not only are they harmless, they actually play a vital part in keeping us healthy.

Bacterial army manoeuvres

The power of DNA sequencing means that we can now interrogate our inner armies as to their make up under different conditions, because each type of microbe has a distinctive genome. The first thing to emerge is a dramatic shift in the balance between the major sub-families in obese individuals, be they mice or humans. That is, obese animals have about half the number of Bs and double that of Fs, compared to normal. And the link here is that the bug switch alters the pool of genes available, the upshot being increased energy harvest from nutrients consumed. In other words the switch helps animals get fatter.

It’s possible to breed mice that do not have any gut bugs and ask what happens when you transfer a colony from another animal. Bacteria-free mice on receipt of a normal gut army promptly double body fat: microbiota transferred from obese mice makes ’em twice as fat and, remarkably, human gut microbes from someone who’s obese also makes mice obese, if fed a high-fat rather than a normal diet.

Chemical warfare

Because we use antibiotics on a massive scale to control infections, we might ask whether they cause the good guys to suffer what the military call collateral damage – the point being that antibiotics don’t target bacteria on the basis of whether they’re good for us or potentially fatal. Inevitably, it turns out that ‘good guys’ do get hit by some antibiotics, and when this happens mice gain weight and build up fat. Unsurprisingly, a high-fat diet makes things worse. The sequence is that the drug changes the balance in microbiota before mice become obese and – a real shock – one course of antibiotic treatment imprints these effects on the animal permanently: it acts for life.

To clever for our own good

In our panic to avoid obesity and still pander to our sweet tooth, mankind has taken to using artificial sweeteners on a massive scale in the mistaken belief that these low-calorie agents do no harm. Only recently has this come to light as yet another example of the old adage about there being no such thing as a free lunch. It’s remarkable: saccharin, the most commonly used artificial sweetener, causes big shifts in the proportions of different types of gut bacteria – some increasing whilst others go down – the overall effect again being much more efficient energy harvesting from food. This is a direct effect of saccharin on the bugs, blocked by commonly used antibiotics.

The story so far

The regiments from which our foot soldiers are drawn (i.e. the species that form the microbiota) affect our metabolism and in particular can influence obesity – and that’s inextricably linked with type 2 diabetes and heart disease. With that in mind, it seems obvious that upsetting them with drugs is a risky business. What’s more, seemingly harmless food supplements can also be fraught with danger.

Marching to a beat

Yet another amazing feature of our inner army is that it keeps time. That is, the abundance of different sub-types fluctuates in synchrony with the day/night cycle. Put another way, it marches to a circadian rhythm along with many other physical, mental and behavioral changes that respond mainly to light – and hence roughly follow a 24-hour cycle. These can be big changes in composition: a particular type of bug can double in amount in 6 hours and return to its initial level by 6 hours later. One of the most familiar examples of the importance of biological rhythms comes from upsetting them by flying long distances on an east–west axis. Sure enough, mice have the same problem and, just like us, their clock is disturbed by jet lag (rather than shuttling them business class across the Atlantic you can simulate the effect simply by shifting the light-dark cycle under which they live forwards or backwards by 8 hours every three days). This largely blocks microbiota rhythmicity, the overall effect being to reduce the total number of bacteria. This in turn raises blood sugar level and the mice become obese. These events are absolutely dependent on what has happened to the microbiota because they are replicated in germ-free mice after transfer of jet-lagged faeces.

That’s more astonishing than might appear at first glance because it places the daily variation in gut bug populations alongside the basic circadian rhythms of the sleep-wake cycle, body temperature and other important functions. Circadian rhythms are driven by a ‘master clock’ in the brain that coordinates all the body clocks so that they are in synch. Four proteins are at the heart of the clock (CLOCK and BMAL1, highly expressed during the light phase, and cryptochromes (CRYs) and period proteins (PERs) expressed in the dark phase). These regulate the expression of many genes, thereby controlling the overall response (see Twenty More Winks). The implication is, therefore, that far from being a kind of add-on that occasionally gets upset, our microbiota play central role in a healthy body.

A recent example of it doing just that comes from another mouse model showing our ‘inner organism’ acting to protect against bacteria from the outside world. In response to infection, cells that line the small intestine switch on the production of a particular sugar (fucose): that is then released from the cells and consumed by members of the microbiota – this novel energy source seemingly helping the host to survive the onslaught of infectious microorganisms.

And finally …

All this stuff about germs being our best friends is riveting but what about the important question? Well, there appears to be a complex interaction between diet, microbial metabolism and colorectal cancer, with bacteria able to make some agents that protect against cancer and some others that drive carcinogenesis. There’s evidence that a wide range of tumours can be promoted by transferring microbiota to germ-free mice and, on the other hand, that depleting intestinal bacteria reduces the development of liver and colon cancers.

Space invaders

Personal space is, apparently, a big thing for many of us these days. So big that ‘scientists’ have had a go at measuring it – they never miss an opportunity do they? Actually, boffins being boffins, they measured something called the defensive peripersonal space (DPPS) – a ‘vital safety margin surrounding the body’ – by sticking a pair of electrodes to the wrists of volunteers who held their hands different distances from their faces whilst receiving bursts of current through the electrodes. That made them blink (!) and the nearer the hand to the face the more they blinked, as the shock was perceived to be a greater threat to their face. There is, seemingly, a sharp boundary: up to somewhere between 20 cm and 40 cm is a high-risk area where we get very aerated: beyond that we don’t much care – with large personal variations depending on how twitchy you are. Debrett’s, which styles itself as the arbiter of society etiquette, has a simpler test, its distilled wisdom revealing that if you can feel the warmth of someone’s anxious breath upon your face, then you’re standing too close.

With all this neurosis it’s probably a good job no one mentioned our inner army: a ten-to-one cellular takeover (albeit that bugs are much smaller) is not so much a bit of heavy breathing as a blitzkrieg. Even so, it’s a delicately poised occupation upon which we depend for survival – and it’s one that we disturb at our peril.

References

Sambo, C.F. and Iannetti, G.D. (2013). Better Safe Than Sorry? The Safety Margin Surrounding the Body Is Increased by Anxiety. The Journal of Neuroscience 33, 14225-14230; doi: 10.1523/JNEUROSCI.0706-13.2013.

The Long and Short of Life

Many years ago (in 1928 to be precise) one of the cleverest of all scientists, J.B.S.Haldane, wrote an essay that became famous for explaining why there is a best size for every animal. In On Being the Right Size he pointed out that the giants who beset the hero of The Pilgrim’s Progress had a problem, unmentioned by John Bunyan, in being not only ten times the height of ordinary man but ten times as wide and ten times as thick. They were therefore one thousand times heavier and, as the human thigh-bone fractures under about ten times our normal weight, the giants would have broken a leg at every step.

Going in the other direction, so to speak, JBS noted that insects don’t have oxygen-carrying bloodstreams because what little oxygen their cells require can be absorbed by simple diffusion of air through their bodies. That’s because gases can diffuse easily through very small distances but are slow to spread further afield – meaning that regions of an insect more than a quarter of an inch from the air would always be short of oxygen. In consequence hardly any insects are much more than half an inch thick and we can relax, safe in the knowledge that the giant, man-eating spiders beloved of science fiction are indeed the stuff of fantasy.

Solving the problem

Larger animals have to take a radical approach to the problem of supplies – Bunyan’s giants needed a thousand times as much food and oxygen as ordinary man and their levels of waste production don’t bear thinking about – the point being that bigger creatures, even if not giants, required the evolution of oxygen-carrying bloodstreams and pumping systems to reach all their cells.

Ostrich racing

Ostrich racing

So successful has this ploy been that, from the emergence of the first fish and amphibians 500 million years ago, we have 64,000 vertebrate species today. Their range is truly astonishing – from tiny frogs less than half an inch long found in Papua New Guinea to the blue whale, averaging 110 tonnes and 24 metres in length and thought to be the largest animal of all time. The African bush elephant is the largest land animal (about 5 tonnes) and birds can get up to 150 kg if they give up flying. At that size ostriches are big enough to race each other whilst mounted by humans. It’s difficult to say whether the birds would rather be flying but if they fancy a bit of reverse evolution they’re going to need to lose 90% of their weight. The fact that only by limiting themselves to about 15 kg can birds manage to get airborne is one indicator of the energy required for flight. Three at this edge of evolution are the Andean condor, the wandering albatross and various bustards, each needing a wingspan of around three metres to generate the lift required to get something like 15 kg into the air.

The point about all these wonderful creatures is that they’ve evolved to survive in very specific niches where they live life on a knife-edge. Recall the Manchurian Great bustard who put on a bit of weight and seemingly lost the capacity to fly: his wing muscles couldn’t generate enough lift to get his 21 kg airborne. Or hummingbirds some of which can manage thousands of wing beats per minute but are constantly on the verge of starvation because they need to drink more than their own weight in nectar each day to generate the energy they use.

Top of the class

One of these marvellous vertebrate species is, of course, us – Homo sapiens – and we’ve been diligently carving out our niche for the past 200,000 years. Allegedly because of our larger brains, we’ve been more successful than any other species and managed to colonise pretty well every corner of all seven continents. That shows amazing adaptability for one species – a bunch of animals that are, to a first approximation, genetically identical. Ah! What a splendid word approximation is. We are indeed 99.9% identical in the genetic code – the sequence of bases in our DNA – that makes us. But we all know, of course, that we are not identical. We’re so not identical that everyone is almost instantly distinguishable from the other seven billion souls elbowing each other for living space on the planet. Two of our most obvious features are skin colour, variations in which have helped us make our homes in hot and cold climates alike, and height. The height range for adults is quite remarkable – from 2 ft (under 60 centimetres) to 8 ft 6 in (over 260 cms) – although exceptional height variation (20% deviation from the average) within a population is sometimes due to medical conditions. Mention of populations raises another familiar point: average heights vary significantly between human populations. Thus for males in the UK and the USA it is 5 ft 10 inches, in Vietnam and Bolivia it’s 5 ft 5, in Japan 5 ft 7 and those Scandinavian chappies clock in at 5 ft 11 inches. Our northern relatives are an example of the rule named after the nineteenth-century German biologist Carl Bergmann who noted that for closely related populations within a species those of larger size are found in colder environments, whilst the smaller guys stick to warmer regions.

What makes humans differ in height?

Nearly identical though we are, the answer has to lie in our genetic material or, more precisely, in the sequence of bases (A, C, G and T) that make up DNA. The difference lies in the detail: in the one in a thousand of the three thousand million bases that make up our genomes that differ between you and me (see Policing DNA). Known as common genetic variants, these inherited differences are what make us unique. The advent of high-powered DNA sequencing methods in the last 10 years means we can now screen large numbers of genomes to pin down the variants that associate with diseases and traits. Several such studies have focused on height and the most recent has sequenced DNA from more than 250,000 people and found nearly 700 variants that account for about 20% of the hereditability of height.

That says there’s still more to be discovered but the basic message is that a very large but finite number of variants, i.e. several thousand sequence differences, each by itself insignificant, contribute an overall effect – how tall you are – even though other factors, notably childhood nutrition, can play a role. Although the DNA variants are scattered throughout the genome, it seems likely that their effects are concentrated on specific pathways involved in cell proliferation and skeletal development.

Why are we interested in height?

In A Taxing Inheritance we tried to explain that, although cancers are mostly driven by the accumulation of mutations, i.e. changes in DNA that alter the activity of proteins and accumulate throughout life, about one in ten are given a kind of flying start when a mutation occurs before birth – i.e. they occur in an egg or sperm cell or just after fertilization. However, the number of such mutations that have been discovered accounts for only about a quarter of inherited breast cancers. The rest get their initial impetus from common genetic variants, in a way that closely parallels the regulation of height by a sub-set of variants. That is, differences at single positions within the genetic code – on their own insignificant – can, in combination, produce a significant effect. When the effect is an increased risk of cancer it may take many years to show itself whereas the impact on height becomes apparent early in development.

A good question

Having used height as an example of common genetic variants in action, one might ask the rather obvious question of whether there is any link between height and cancer and indeed several studies have shown that there is. In a large group of postmenopausal women (over 20,000) height was positively associated with risk of all cancers, every four inch change in height giving a 13 percent increase in risk. Another study concluded that tall men have slightly higher risk for aggressive prostate cancer.

Keep calm!

So there’s a link between being tall and cancer – but don’t panic! Like a good few other things in life, there’s nothing you can do about it. Bear in mind that, cancer apart, tallness, particularly in men, may be a boon and not just when you’re trying to watch footy. There’s evidence that shorter adults (below 160.5cm / 5ft 3in) are about 50% more likely to have a heart attack or die from heart disease than tall people.

Finally, this piece is to make the point that there isn’t a ‘height gene’ – just a large number of permutations in the variable bits of our genomes that determine how lofty we become. Similar permutations also determine most of the risk of inheriting breast cancer but we can’t do anything about that either. So the long and short of it is love the science – and love your size!

References

Wood, A.R. et al. (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics 46, 1173–1186.

Kabat, G.C. et al. (2013). Adult Stature and Risk of Cancer at Different Anatomic Sites in a Cohort of Postmenopausal Women. Cancer Epidemiol Biomarkers Prev., 22, 1–11.

Zuccolo, L. et al. (2008). Height and Prostate Cancer Risk: A Large Nested Case-Control Study (ProtecT) and Meta-analysis. Cancer Epidemiol Biomarkers Prev., 17, 2325–2336.

Cairns, B.J. and Green, J. (2013). Good News for “Alice”: Height and Sex Differences in Cancer Risk. J Natl Cancer Inst djt127 doi: 10.1093/jnci/djt127

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.”

 

Wake up at the back

Living with someone of the opposite sex, or getting married as it used to be known, is an interesting experience. One of the things you rapidly discover that your Mum never warned you about is that women are a distinct species.  You missed that revelation in your biology classes? Serves you right for snoozing on the back row but, as a recap of the evidence, consider the following. Species often show major differences in sensory perception – thus our cat is much better than I am at seeing in the dark, though he misses out a bit in daylight as cats don’t have colour vision. When it comes to hearing it’s a bit the other way round: most of the time you can shout at him til you’re hoarse with absolutely no effect – but one faint clink of a food bowl at the back door and, yet again, he’ll set a new Feline Fifty metres Steeplechase record from the front garden. And dogs, as is well known, hear frequencies way beyond what we can pick up.

Not in my lectures!!

The gentle sex has similarly evolved beyond what mere man can manage. Take colour, for example, at which men are, as we’ve noted, quite good – compared to cats. But, as you discover the first time you are taken ‘clothes shopping’ by your wife, other half, inamorata, partner, mistress or whatever, women have evolved far beyond merely spotting that blue is different from red and being able to recite Richard Of York (to remind themselves of the rainbow sequence). They see ‘combinations’ – so you are curtly informed that what has taken your fancy ‘just doesn’t go together’ in the sort of voice that adds ‘any nitwit can see that’ without the need to expend breath on the last seven syllables.

They’re at a similarly lofty level of evolution when it comes to sound. My lady wife avers that I snore – all the time (when asleep, that is) and very loudly. So much so that she tends to use a bed at the opposite end of the house for sleeping and only ventures within sonar range for other purposes. I’d always explained this behaviour as a manifestation of the amazing imagination possessed of the female that us boys are, of course, completely lacking. However, I’ve now come to appreciate that, like Fido (who sleeps in the kitchen), she simply has exquisitely sensitive aural apparatus. So maybe I do snore – but only very quietly or at ultra high frequency, so that I would be undetectable at rest to my own species and only my beloved and the dog would know what was going on (oh, and the cat because he can see the heaving chest).

Which is very reassuring since some fellows at the Universities of Wisconsin and Barcelona have got together to discover that snoring makes you nearly five times more likely to develop cancer. Strictly the problem is sleep disordered breathing (SDB) – which happens when there’s some kind of blockage of the upper airway and, apart from disrupting sleep, it can make you snore. Of course, there’s evidence that sleep disruption can contribute to all sorts of problems from heart disease to car crashes but this is the first study making a link to cancer.

No problem for me (discounting the wife’s super sonar) but should real, habitual snorers panic? Please don’t for most of the usual reservations to this type of study apply – relatively small numbers (1522) for example. The volunteers came from an alluringly named body of men and women called the Wisconsin Sleep Cohort, set up in 1988 for prospective studies of sleep disorders. In fact the interesting ones here are what we might call the Winsomniacs – the 365 of the Cohort who can’t do it rather than the majority of Badger State dreamers. Split in this case into sub-groups of SDB severity – the strongest association being with the most severe SDB. Although the authors did their best to allow for other factors (obesity – a common cause of SDB – diabetes, smoking, etc.) it’s almost impossible in this type of study to eliminate everything bar the one factor you’re focussing on.

The most frequent linked cancer was of the lung, followed by bowel, ovary, endometrial, brain, breast, bladder, and liver. And the cancer risk was up to four-fold greater for the worst afflicted.

Do the boffins have any helpful suggestions? Not really. Those unlucky enough to be severely affected can try a gadget called a continuous positive airway pressure device but, for the rest, console yourselves that the risk is small and the data so far are very preliminary. Put another way, you have more important things to think about – like finding a partner (preferably with sub-standard sonar detection capability) who loves you so much they’re willing to poke you in the ribs whenever you become aurally intrusive.

References

http://www.telegraph.co.uk/health/healthnews/9278214/Snoring-can-raise-cancer-risk-five-fold.html

Javier Nieto, F.J. et al. (2012). Sleep-disordered Breathing and Cancer Mortality: Results from the Wisconsin Sleep Cohort Study. American Journal of Respiratory and Critical Care Medicine 186, Iss. 2, pp 190–194.

Whose side are you on?

Writing this blog – intended to be on current cancer-related topics – has been very good for me, if no one else, because it makes me read things I wouldn’t otherwise bother with. So I’m wiser than I would have been – but here’s a shocking admission: I’m becoming increasingly sympathetic to those who wish that scientists would just go away – or at least shut up sometimes. Of course I’m being jolly unfair: it’s not so much fellow boffins I’m miffed with as the ‘media’ – the BBC and the leading newspapers. They’re the ones who bring ‘stuff’ to my attention. Do you think I spend my time reading a journal called Alcohol and Alcoholism?!

Thanks to the medja, in just the last couple of weeks I’ve read that women’s height is linked to ovarian cancer  (BBC), breast cancer screening results in ‘unnecessary treatment’ (Telegraph), and a glass of wine carries a breast cancer warning (The Independent), – oh, and I should take an take an aspirin a day to cut cancer risk (Guardian). Just a month or two ago there was a similar stampede of ‘beef is bad’. This week the University of Gothenburg weighed in by discovering that some people are so ‘addicted’ to Facebook that they open it the moment they switch on their computers! And getting hooked (to Facebook, that is) makes women unhappy. Thank heavens they didn’t get round to emails or prostate cancer in Gothenburg or I might be needing something stronger than aspirin for my depression.

If you’d looked at all these important scientific surveys you’d have spotted that they have one thing in common: they never mention fun. Not one of them. Ever. Not a smile, nary a joyous feeling – and as for anything orgasmic …

Salvation is at hand

The good news is that some relieving guidance has popped up in the midst of all this ‘thou shalt not’, ‘it’s too late’ and ‘now look what you’ve done’. The absolutely astonishing thing is its source – ‘provenance’ as the antiques freaks like to put it. You aren’t going to believe this but it’s to the good old Church of England that we turn in the shape of a vicar from Hove (go on then …). This blessed man has revealed that not only is it a ‘good thing’ but it’s almost a moral duty, perhaps even a religious obligation, to spend Easter Sunday in bed, eating chocolate and having sex – and, by implication, doing anything else that feels as though it should be in the ‘naughty but nice’ statistical bracket. Well – who would have thought you’d read it here – praise be for the C of E!            Photograph by Hemera/Thinkstock

Here comes another of them scientists

Having let the grumpies have their say, shall we do as we preach and have a balanced, non-inflammatory comment on behalf of beleaguered boffins? Oh alright. Should the studies I listed have been done? Yes (apart from the Scandi one, obviously). They’re by excellent groups and they add another brick to the wall, even if it’s only reaffirming what we knew. The ovarian/height link paper makes a good case by pointing out that the evidence so far published on whether height, weight and body mass index (BMI) have any link with the risk of getting ovarian cancer has not given a very clear picture. They were thus prompted to put together 47 of these studies (a meta analysis) – and what emerged was that the risk increases with height and, for women who have never used hormone therapy, with BMI. However, the important point is that although the increases are statistically significant, they are very small. My colleague Paul Pharoah has helpfully estimated that they show that being 5ft 6in rather than 5ft tall raises the lifetime risk of ovarian cancer from about 16 in 1000 to 20 in 1000.

So these reports are good, though not seismic, stuff. And yes, it’s great that the media pick up on what science produces and bring it to the attention of the wider world. It would just be nice if they were less keen on eye-catching, doomy, headlines. How about taking a lead from The Sun, an organ not previously mentioned in this column, that headlined the C of E story with Easter Sinday. What might they do? Aspirin v. Expirin? I came up with a cracker for the ovarian study but a problem with talking and writing about cancer is the ease with which jokes (mine anyway!) teeter into what some would consider to be the realms of bad taste. So a green light for The Sun then!

Final thought for the day: am I now (1) religiously taking aspirin OR (2) opting for Nick the Vic’s life support strategy? I think you know the answer to that one.

References

Collaborative Group on Epidemiological Studies of Ovarian Cancer (2012) Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies. PLoS Med 9(4): e1001200. doi:10.1371/journal.pmed.1001200

Kalager, M., Adami, H.O., Bretthauer, M. and Tamimi, R.M. (2012). Overdiagnosis of Invasive Breast Cancer Due to 491 Mammography Screening: Results From the Norwegian Screening Program. Annals of Internal Medicine 156, 491-499.

Rothwell, P.M., Wilson, M., Price. J.F., Belch, J.F.F., Meade, T.W. and Mehta, Z. (2012). Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. The Lancet, Early Online Publication, 21 March 2012 doi:10.1016/S0140-6736(12)60209-8Cite or Link Using DOI

Fancy that?

Seeing as they started 28 years ago we can hardly blame members of the Harvard School of Public Health for publishing the results of their labours in tracking 120,000 people, asking them every few years what they’ve eaten and seeing what happened to them (a ‘prospective’ study). About one in five of the subjects died while this was going on but the message to emerge was that eating red meat contributes to cardiovascular disease, cancer and diabetes. The diabetes is non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes – about 90% of diabetes cases. The cancers weren’t specified, although the evidence for a dietary link is generally strongest for colon carcinoma. The risk is a little higher for processed red meat than unprocessed.

How much?

Massive, if you mean the amount of data they accumulated from such a huge sample size followed over many years. If you mean on a plate, their standard serving size was 85 grams (3 ounces) for unprocessed beef, pork or lamb) and 2 slices of bacon or a hot dog for processed red meat. One of those a day and your risk of dying from heart disease is increased by about 20 per cent and from cancer by about 10 per cent – and the risks are similar for men and women. Just to be clear, that is a daily consumption – and the authors very honestly acknowledge that ‘measurement errors inherent in dietary assessments were inevitable’. They also mentioned that one or two things other than steak can contribute to our demise.

Are we any wiser?

If you recall from Rasher Than I Thought? the risk of pancreatic cancer is increased by just under 20 per cent if you eat 50 grams of processed meat every day. This report suggests that a limit of 1.5 ounces (42 grams) a day of red meat (one large steak a week) could prevent around one in 10 early deaths. So does it tell us anything new? Not really. Was it worth doing? Yes, because it adds more solid data to that summarized in Are You Ready To Order?

And the message?

Unchanged. Do some exercise and eat a balanced diet – just in case you’ve forgotten, that means limit the amount of red meat (try fish, poultry, etc.), stick with the ‘good carbs’ (vegetables, fruits, whole grains, etc.), cut out the ‘bad’ (sugar – see Biting the Bitter Bullet), eat fishy fats not sat. fats and, to end on a technical note, don’t pig out.

 References

Pan A, Sun Q, Bernstein AM; et al. Red meat consumption and mortality: results from 2 prospective cohort studies [published online March 12, 2012]. Arch Intern Med. doi:10.1001/archinternmed.2011.2287.

Pan A, Sun Q, Bernstein AM; et al. Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. Am J Clin Nutr. 2011;94(4):1088-1096.

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.

Obesity and Cancer

Science, you could say, comes in two sorts. There’s the stuff we more or less understand – and there’s the rest. We’re pretty secure with the earth being round and orbiting the sun, the heart being a pump connected to a network of tubes that keeps us alive, DNA carrying the genetic code – and a few other things. But human beings are curious souls and we tend to be fascinated by what we don’t know and can’t see – why the Dance of the Seven Veils caught on, I guess.

Scientists are, of course, the extreme example – they spend their lives pursuing the unknown (and, as Fred Hoyle gloomily remarked, they’re always wrong and yet they always go on). But in this media era they pay a public price for their doggedness because they get asked the pressing questions of the moment. Is global warning going to finish us off soon, why is British sport generally so poor and – today’s teaser – does being fat make you more likely to get cancer?

A few facts go a long way

The major cancers have become familiar because the numbers afflicted are so staggering – but the one good thing is that the epidemiology can tell us something about the disease. Thus for cancers of the bowel, endometrium, kidney, oesophagus and pancreas and also for postmenopausal breast cancer there is clear evidence that being overweight or obese makes you more susceptible. In other words, if you compare large groups with those cancers to equally large numbers without, the disease groups contain significantly more people who are fat. We should add that the above list is conservative. A number of other cancers are almost certainly more common in those who are overweight (brain, thyroid, liver, ovary, prostate and stomach tumours as well as multiple myeloma, leukaemia, non-Hodgkin lymphoma and malignant melanoma in men).

Sizing up the problem

The usual measure is Body Mass Index (BMI) – your weight (in kilograms) divided by the square of your height (in metres). A BMI of 25 to 29.9 and you’re overweight; over 30 is obese. In England in 2009 just over 61% of adults and 28% of children (aged 2-10) were overweight or obese and of these, 23% of adults and 14% of children were obese. And every year these figures get bigger.

How big is the risk?

Impossible to say exactly – for one thing we don’t know how long you need to be exposed to the risk (i.e. being overweight) for cancer to develop but in 2010 just over 5% of the total of new cancer cases in the UK was due to excess weight. That’s another conservative estimate, but it means at least 17,000 out of 309,000 cases, with bowel and breast cancers being the major sites.

What’s going on?

Showing an association is a good start but the important thing is to find out which molecules make that link. For obesity and cancer detail remains obscure but broad outlines are emerging, summarised in the sketch. In obesity fat (adipose) cells increase in both number and size (so it’s a double problem: more cells – and the fat cells themselves are fatter). As this happens other cells are recruited to adipose tissue and, from this cellular cooperative, signalling proteins are released that have the potential to drive tumours. This picture is similar to that of the microenvironment of tumours themselves, where many types of cell infiltrate the new growth. Initially this inflammatory and immune response aims to kill the tumour but if it fails the balance of signalling shifts so that it actually helps the tumour grow. In addition to signals from fat cells themselves, obesity is usually associated with increased levels of circulating growth hormones (e.g., insulin) and of lipids, both of which may also promote tumour development.

Thus many signals with cancerous potential arise in obese individuals. In principle these could initiate tumour growth or they could accelerate it in cancers that have started to develop independently of obesity. So it is complicated – but at least as new signalling strands emerge they offer new targets for drug therapy.

In obesity abnormal signals from fatty tissue can combine with others arising from perturbed metabolism to help cancers develop

Reference

World Cancer Research Fund (WCRF) Panel on Food, Nutrition, Physical Activity, and the Prevention of Cancer (WCRF, 2007).

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.