Johns Hopkins: cancer is primarily ‘bad luck’

Two scientists at Johns Hopkins Kimmel Cancer Center, Dr. Bert Vogelstein, the Clayton Professor of Oncology at the Johns Hopkins School of Medicine, and ‘bio-mathematician’ and assistant Professor, Cristian Tomasetti, Ph.D. published a study on January 2nd in the journal Science, which concluded that two-thirds of adult cancer incidence across tissues can be explained primarily by ‘bad luck’.

The scientists created a mathematical model by searching the scientific literature for information on the cumulative number of divisions of stem cells among 31 tissue types during an average individual’s lifetime. They then charted the number of stem cell divisions in these tissues and plotted them against the incidence of cancer. For example, in colon tissue there are 4 times more cell divisions than occur in the small intestine, and cancer is more prevalent in the former. QED.

“It was well-known that cancer arises when tissue specific stem cells make random mistakes, or mutations during cell replication”, said Vogelstein.

Let’s get real

1. Firstly, neither prostate nor breast cancer were covered in the research since the researchers could not obtain reliable data on stem cell divisions. So that would rule out almost one third of all cancers in the UK. And we are always being told by the UK ‘Brand leader’ Cancer Research, that these are largely hormonally driven, with factors such as oestrogen, lack of exercise and obesity playing a big part. If the new research is correct, and it were to apply to breast and prostate cancers as well, how has CRUK made such a big error? Just bad luck, perhaps?

2. Secondly, I will hazard a guess that the number of stem cell divisions in a tissue occurs in line with the number of overall cell divisions. And what the scientists actually showed was that there was a link between more cell divisions in a tissue and an increased risk of cancer. Hardly, new thinking really.

3. But if it is all about stem cells do the conclusions mean that someone in New York has many more stem cell divisions in their lungs than someone in China, or Kenya, where cancer incidence is considerably lower? The UK population must have 4 times the stem cell division of Thais; with almost exactly the same population we get four times the number of cancers they do. Why would that be?? Would the increased rate of stem cell division in New York or London not constitute a cause? Or are Thais just four times luckier than Londoners?

4. Next, having shown a link between cell division volumes and cancer volumes, our plucky duo made a mental jump: “It was well-known that cancer arises when tissue specific stem cells make random mistakes, or mutations during cell replication”, Well known to whom? In 2012 scientists were still arguing whether there was such a thing as a cancer stem cell.

And the idea that cancer is caused by mutations to the core DNA is quaintly old fashioned. Indeed the modern theory of cancer (being confirmed by scientists week in, week out) is that not much happens to the core DNA (and when it does the immune system easily spots it as rogue). Instead, chemicals like homocysteine build up in the blood stream and cause more methylation around the DNA coil. This holds histones in place, which in turn hold the integrity and shape of the DNA in the nucleus.

When the histones cover a gene responsible for, say, controlled cellular division, it cannot send out its messages, it is silenced, and the cell starts dividing randomly. It is important to note that this methylation and acetylation is believed to be reversible by literally thousands of scientists currently working for drugs companies and University Medical Schools. The science is called Epigenetics (Epi=around, the gene). Drugs companies believe they can affect the methylation and acetylation directly; or indirectly via the enzymes that cause it.

Other scientists believe that there are a host of natural compounds (from sulphoraphanes to carotenoids) that can do this, as can exercise hormones. Indeed, Epigeneticists argue that there are clearly 4 causes of DNA blockages – environmental toxins, stress, poor diet and hormones such as oestrogen.

So, are these epigenetic scientists all wrong?

Where hypotheses and statistics meet

A statistician is someone who will tell you that it’s better to have a watch that is broken (it is right twice a day), than one that loses 7 minutes a day (it is right once every thirteen days).

I have decided to look at road accidents in Britain (London and Manchester were excluded because there were no reliable statistics). Now, it is widely accepted that council road administrators allow too many non-UK-qualified lorry drivers to drive on the roads. And sure enough, we have found that the number of road deaths is proportional to the increases in foreign lorries on our roads. It doesn’t fit exactly (but to about an 80% level) and it differs by the 31 regions we looked at. So if you die in a road accident it has little to do with your skills as a driver, or how fast you were going, or the weather conditions. The number of foreign lorry drivers being allowed on our roads by a lack of legislation is behind it. Just bad luck really.

What is odd though is that this conclusion doesn’t hold true in Africa or China. So I’ll leave that out of my model.

Implications

So, thanks to Johns Hopkins, science has a new bed fellow: Bad luck. It’s the devil’s work. No need to feel guilty about your gluttony and sloth – just ‘eat drink and be merry, for tomorrow ye may die’.

No need for CRUK or the Government to feel guilty about failing to do anything serious in the way of Cancer Prevention Programmes in the community. You can’t legislate for bad luck. It would be pointless spending billions of pounds telling people to eat healthily, exercise and give up smoking if cancer occurs ‘for no particular reason other than randomness’ (according to Tomasetti).

If 65% of cancers are just bad luck, and we add on the 20% known to be caused by parasites and viruses (according to the WHO), then we certainly aren’t left with much that is to do with our sloth and gluttony. ‘50% of cancers are your own fault’ said CRUK 5 years ago. ‘30-50% of cancers are due to your poor diets’ said the WHO. ‘At least half of all cancers are preventable’. Oh no they’re not says a mathematical model (that left two of the biggest out).

Food companies that sell junk, have no case to answer. Lucky for them. What of the legal cases in the USA where people sue cigarette companies or mobile phone companies for not warning them that their products cause cancer? Presumably your bad luck is now lucky for these companies.

At CANCERactive we were helping a patient with oesophageal cancer. She had had bad acid reflux for ten years and been on a drug the whole time. A trip to the manufacturer’s website said that ‘on no account should the drug be prescribed for more than six months’. The woman asked her doctor what he thought caused her cancer. ‘Just bad luck’ was his reply. Johns Hopkins have vindicated him. His mis-prescription of the drug was irrelevant.

But there’s a get out clause in the model: “We found that the types of cancer that had a higher risk than predicted by the number of cell divisions, were precisely the one’s you’d expect” (lung cancer – linked to smoking; skin cancer – linked to sun exposure). So, other factors do cause deviation from their model. Lucky, I spotted that.

Junk science

The new science of ‘Bad luck’ is a dangerous concept. It removes the need for people to exert any self-control. The implication is that you can make little difference to prevent your cancer (and thus can make little difference to prevent it returning – so it is pointless doing anything to help treat your condition). Self-empowerment for patients goes out of the window. You might as well stay fat, not exercise, carry on smoking and just place your total faith in your good doctor’s hands. And luck.

Except, isn’t it lucky for us that The American Cancer Society have produced a 2012 report saying that since 2006 there has been an ‘explosion’ in research, and ‘overwhelming’ evidence that good diet, weight control and exercise can increase survival and even prevent a cancer returning.

Except, isn’t it lucky for us that the Karolinska Institute has produced straight line graphs on the links between cows’ dairy consumption and prostate, breast and ovarian cancers; or that Bristol University produced a meta-study on 52 research reports concluding that people who exercised regularly developed less cancers, and that those with cancer who exercised regularly, survived longer.

Watch out for the follow up study: ‘It is just bad luck that the chemotherapy didn’t work for you’. (Well it wouldn’t anyway because there is no drug available today that tackles cancer stem cells.)

What bad luck.

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New blood test tracks cancer development

Scientists at the CRUK Institute at Cambridge University have managed to follow the progress of cancer in people by following traces of tumour DNA circulating in patients’ blood (ctDNA).

Importantly this also allows scientists to identify tumour changes and chemotherapy drug resistance (Nature).

The scientists followed 6 patients with advanced breast, ovarian and lung cancers over two years taking blood samples at regular points, and by looking for changes in the tumour ctDNA before and after each course of treatment, they were able to identify which changes in the tumour’s DNA were linked to drug resistance following each treatment session.

Using this new method they were able to identify several changes linked to drug-resistance in response to chemotherapy drugs such as paclitaxel (taxol) which is used to treat ovarian, breast and lung cancers, tamoxifen which is used to treat oestrogen-positive breast cancers and trastuzumab (Herceptin) which is used to treat HER2 positive breast cancers.

Dr Nitzan Rosenfeld one of the study authors, said: “Tumours are constantly changing and evolving which helps them develop a resistance to many of the drugs we currently give patients to treat their disease”.

“We’ve shown that a very simple blood test can be used to collect enough tumour DNA to suggest to us what parts of the cancer’s genetic code is changing and creating tumour resistance to chemotherapy or biologically-targeted therapies”.

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Beating cancer with chemotherapy and better drugs

The mythology of cancer sees many claims. One of which is that we are beating cancer due to earlier diagnosis and better drugs. Let us consider the available research on chemotherapy – for almost every cancer patient treated with drugs is still, inevitably, given at least one round of good old chemotherapy.

Available research evidence does indeed point to chemotherapy having a positive effect for some cancer patients.

Let’s start here:

(1) The Department of Oncology at North Sydney Cancer Centre in 2004 published a report evaluating chemotherapy over the years and concluded that ‘it only made a minor contribution to survival’. The figures they came up with were 2.3% in Australia and 2.1% in America. In Britain there are 320,000 people diagnosed with cancer a year. About 60 per cent have chemo (although some of these people do not actually have cancer and were misdiagnosed by mammograms etc). Being generous and assuming no misdiagnoses, that would mean that chemotherapy had an effect on about 3,600 people. I cannot tell you from the research whether ‘effect’ means they were cured or whether they reached 5-year survival, or what. Sorry, I didn’t find the research very clear on that point.

(2) Somewhat alarmingly, last year we had the report from the Fred Hutchinson Cancer Center in Seattle that concluded ‘Chemotherapy can cause cancer to return’. Note that they did not say, ‘we know cancer can return after chemo’, which is how Cancer Research responded to this study. They said CAUSE – apparently chemotherapy can cause healthy cells to produce a protein WNT16B and this is taken up by cancer cells – it helps them re-grow and even protects them from the next round of chemotherapy.

You may feel that all this misses an important point and that drugs have moved on – chemo is past it; old hat: Drugs like Tamoxifen, Aromatase Inhibitors and Herceptin are not really chemotherapy agents, and you’d be right. In 2012 a couple of reports shed some light on the current state of play.

(3) Firstly, one study (lead by Professor Carlos Caldas – reported in Nature) had Cancer Research all excited. A ‘landmark study’ from their Cambridge Institute showed there were 10 different ‘clusters’ of breast cancer types. ‘No longer does one size fit all’ they cried at CRUK. (It would be churlish of me to mention that CANCERactive have been saying that for ten years, but what the heck). In the future CRUK are suggesting they can more accurately develop treatments for each cluster. The problem at the moment is that there are only treatments for two of the clusters, the Tamoxifen/AIs one and the ‘HER-2 targeted therapy using Herceptin’ cluster. So here’s a real improvement: 2 out of 10 is better that 2.3 per cent.

(4) Unfortunately, the excitement was crushed somewhat when three research studies reported on the existence of Cancer Stem Cells at the heart of tumours. A couple of UK cancer centres (Bart’s Hospital and the Blizzard Institute, London) have even isolated these nasty little cells. Apparently, if you don’t kill them off, they can re-grow.

In one of the three studies (from the University of Texas South Western Medical Centre), there were statements such as ‘Cancer Stem cells are in charge of tumours’, and the lead researcher, Dr Louis Parada and the other researchers added, ‘In the past we have tried to get rid of the entire stew of cancer cells. But shrinking a tumour by 50% is irrelevant. No current drugs tackle cancer stem cells – but at least we now know what to go after’.

(5) We are by no means ‘against chemotherapy’ at Junk Science UK, we just think the mythology and the hype needs to be calmed down. Perhaps the final words should therefore go to Duke’s University Medical Centre in Carolina who in their 2012 report concluded that ‘Patients with cancer are largely being mislead into believing that the drug they are being offered is somehow going to cure them’.

Oh dear.

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Everybody is missing the point on screening mammography

A debate has sprung up over the last few weeks. It is not a new debate; it concerns mammography. Recently there has been research that shows 4000 people in the UK are unnecessarily treated as a result of ‘Over-diagnosis’ by screening mammograms. The ‘pro’ side immediately says ‘1300 lives are saved and have to be set against this’. And then journalists from the Telegraph and BBC jump in on the act. Unfortunately, few know their facts. I won’t be updating our article on mammography at CANCERactive because, as usual, we were well ahead of this debate. What I thought you might like to read is the essence of my piece to the Telegraph, and why I think everybody seems to be missing the important issue:

Firstly, there is no confirmed research data that mammography saves 1300 lives a year in the UK. Until recently the Cancer Research UK website admitted that fact. There are various studies and reports, for example, showing the figures of 1300, 850 and zero. Take your pick.

Secondly, whilst people have been debating issues such as over-diagnosis and unnecessary treatment and distress, the debate has missed the fact that mammography can likely cause breast cancer. For example, about 25 per cent of breast cancers are linked to inherited genes where the person usually has one of the pair defective, and only one operating correctly. American research is quite clear that these people are at greater risk of developing breast cancer if sent off from an early age for an annual mammogram ‘to be safe’. The cumulative radiation is statistically far more likely to damage a single gene than a pair.

Thirdly, some ‘diagnosed’ women consider having double mastectomies. The idea of a double mastectomy is palpable non-sense with no evidence whatsoever in terms of numbers over who might have been prevented from developing cancer! Cancer is an all over body disease with symptoms like cancer markers, low blood oxygen and poor immune response evident throughout the body. If you have a BRCA1 or 2 problem, it will cause poor immune recognition or DNA replication control everywhere in your body. If a woman has toxic chemicals in her body, they will not only collect in the fatty breast tissue but in other such tissue too.

Fourthly, to add to the confusion, about 50 per cent of the ‘irregularities’ detected by mammography are lobular, and 50 per cent ductal. While Christies, Manchester were warning some 5 years ago that DCIS could be extremely dangerous and were looking at trials to see which drug might be used to prevent an aggressive cancer developing, at the annual Breast Cancer Symposium in America a paper was presented showing that DCIS was caused by calcium deposits, and 80 per cent never became cancers. The finding that women with the highest blood levels of vitamin D and omega-3 do not develop breast cancer may be linked to their effects with calcium.

European research has shown that depending on the density of the tissue, screening mammography may be only 65 per cent accurate at best. Other studies have shown that in order to detect the cancer it has to be of sufficient size – a size produced by about 20 cell divisions. At 40 you are dead. Screening mammography is neither accurate nor early detection.

How many of the 4000 women who are then unnecessarily treated die as a result of the chemotherapy drugs provided? How many have impairment to their heart and/or lungs as a result of radiotherapy? Is it is more than the 1300? But surely even this question is off the point: Why are we using such an outdated and inaccurate system which can lead to quite barbaric consequences (double mastectomy?).

Surely, the energy, time and the money would be better spent developing blood tests that are already coming through from private companies in Nottingham and America that can spot cancer in the pre-cancer stages.

This argument about screening mammography is completely off the real point and is propagated by vested interests. How many hospitals and cancer centres would be stuck with an expensive machine if an accurate blood test were available tomorrow? (Although I should point out that mammography is the current gold standard once a cancer has been confirmed and further information is required.)

The real question we should be asking is this: ‘How do we develop a simple, accurate and early diagnosis test for cancer?’ The answer has nothing to do with mammography.

For a fuller report see:

http://www.canceractive.com/cancer-active-page-link.aspx?n=1420&Title=Breast cancer screening and cancer risk

http://www.canceractive.com/cancer-active-page-link.aspx?n=666&Title=False Positive Mammograms

http://www.canceractive.com/cancer-active-page-link.aspx?n=671&Title=Mammograms and Obese Women

http://www.canceractive.com/cancer-active-page-link.aspx?n=2644&Title=The Development of Thermal Imaging

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Puzzling prediction of falling cancer death rates made ahead of fund raising drive

According to ‘experts’ at the charity Cancer Research UK, cancer death rates in the UK are set to fall by almost 17 per cent by 2030. And better diagnosis and treatment is the main reason (sic) for the change.  The figures were released in the run-up to Stand Up To Cancer, a fundraising partnership between Cancer Research UK and Channel 4.

This is all rather puzzling because in 2011, when claiming cancer death rates were falling in breast cancer and colon cancer, they predicted an increase in the number of cancer cases and deaths from cancer as the population ages over the next twenty or so years.

The ‘experts’ also claim that the improved outlook reflects the fact that fewer people are smoking. So is ‘prevention’ really the key? Or could it even be something else?

To quote from the CRUK press release, ‘In 2010 an estimated 170 people in every 100,000 members of the general population died from cancer. By 2030 this is forecast to fall to 142 per 100,000.

Ovarian cancer is expected to see the biggest drop in numbers of patients dying, at 42.6 per cent. Incidence of the disease is expected to reduce from 9.1 women per 100,000 to 5.3 per 100,000 by 2030. Death rates for breast cancer are predicted to fall by 28 per cent, for bowel cancer by 23 per cent and prostate cancer by 16 per cent.

A few cancers show a reverse trend, with larger numbers of people dying. Death rates for oral cancer are likely to rise by 22 per cent, as incidence rises from 2.9 to 3.5 per 100,000 people. For liver cancer, death rates are predicted to go up by 39 per cent, with incidence increasing from 4.2 to 5.9 per 100,000’.

Professor Peter Sasieni, Cancer Research UK epidemiologist at Queen Mary, University of London, said: “Our latest estimations show that for many cancers, adjusting for age, death rates are set to fall dramatically in the coming decades. And what’s really encouraging is that the biggest cancer killers, lung, breast, bowel, and prostate, are part of this falling trend.

“Because old age is the biggest risk factor for cancer and more people are living longer, they have a greater chance of developing and, unfortunately, dying from the disease. But overall the proportion, or rate, of those who die from cancer is falling.”

Why this is puzzling is because the absolute numbers of cancer cases has doubled in the last thirty years and a team of oncologists working with MacMillan had predicted it would double again in the next twenty years. That would mean about 4 million people with cancer in Britain.

According to the 2011 census, the population for England and Wales has increased by 3.7 million from 2001; and (to quote) ‘buoyed by increased life expectancy, sustained immigration and robust fertility levels, the number of residents jumped 7.1% from 52.4 million in 2001 to 56.1 million in 2011’. If that continues, in twenty years time we will have about 65 million people in England and Wales in 2031. According to figures about 350,000 ‘older’ people are retiring abroad each year, while about 650,000 younger foreign people are coming into the country.

And it should be noted that Cancer Research ‘experts’ are not talking about total numbers of cases of cancer, nor total numbers of deaths. But the rate per 100,000 of population. So if the number of people increasing the population by 7 per cent due to ‘sustained immigration and robust fertility levels’ continues you might expect a decline in cancer death rates anyway. Especially if the average age falls across the population.

The other claim that is interesting is that the main reason is due to better diagnosis and treatment. Three years ago CRUK said it was all down to better diagnosis and treatment and I chided them at the time. They conveniently ignore the fact that over two thirds of cancer patients now build their own integrative treatment programmes, search the Internet for alternative treatments, visit complementary centres that are independent (like Maggie’s, The Haven and Penny Brohn) or part of the Hospital (like the Butterfly Centre and the Rainbow Centre). Some people even take themselves off abroad for life-extending treatments. Then there has been an explosion in coverage of what people can do to help themselves from the utterings of the Daily Mail to charities such as CANCERactive. Only recently the American Cancer Society stated that there had been an ‘explosion’ in complementary research since 2006 and that there was ‘overwhelming evidence that complementary therapies like diet, weight control and exercise could increase survival and stop a cancer returning.

It seems that Cancer Research UK think your personal efforts count for little.

Better diagnosis? It is definitely coming with a possible avalanche of private companies and blood tests, but up to now …  mammograms and PSA tests? The Nordic Cochrane has said that mammograms do ‘more harm than good’, with up to 30 per cent being misdiagnosed (of course you are ‘cured’ if misdiagnosed). The American Preventative services Task Force said much the same about the PSA test.

Better treatments? Well if you read the recent articles on the new breed of biologics, or ‘designer drugs’, such as the article we printed by Professor Karol Sikora, you’d be more than a little underwhelmed. There are alternatives coming – like localised hyperthermia (Ablation, HIFU) but the ‘old school’ is none too happy about the possibility of becoming redundant. And anyway it can’t work on blood and lymph cancers.

And this is another little area that needs attention. Blood and lymph cancers account for about 80,000 cases in the UK currently; twice the number of breast cancers diagnosed. But they are divided into about ten different types – there are four different lymphomas. Yet no one divides breast cancer by ductal or lobular in the overall numbers. It’s also an inconvenient truth that at current growth rates lymphoma could become the number one cancer in the next twenty years.

Old age the biggest risk factor and an ageing population? Recent research shows that the historical 80 per cent of cancers in the over-65 age group is less and less the case. 40 per cent of breast cancers are now developed by women below 60 years of age. Prostate cancer has multiplied six-fold in the forty-something age group; oesophageal cancer has boomed amongst forty-somethings; some child cancers have tripled.

And I just loved the bit about ‘age-corrected statistics’. I really must have my age corrected one day.

If smoking reduction is such a big factor, how come cancer cases are set to double in absolute terms despite a fall in smokers? If prevention is so important why aren’t we doing more about the 50 per cent of cancers that aren’t your fault? Look up most blood or lymph cancers on American web sites. They will tell you about the links to pesticides, toxic ingredients in everyday toiletries and household products, heavy metals, environmental toxins beyond asbestos.

Perhaps the European REACH project, if 1000 toxic ingredients really are cut from personal care, toiletry and household products in the next 15 years, will see a great reduction in cancer levels.

Stand up to Cancer fund raising? Of course if you can convince people that you really are succeeding in beating cancer by doing what you are doing, they may well give you more funds.

Cancer Research UK is a great charity and I am sure it does its level best to help people. It is sad that, if the numbers of people with cancer are going to double in the UK to four million, anybody tries to claim that somehow we are beating cancer because of better diagnosis and drugs, however the numbers are massaged.

I am at this point reminded of MD Anderson’s quote that ‘All the exciting new developments in cancer are coming in areas other than chemotherapy’. I think I will file the press release and bring it out again in 1930 to see what really did happen. Somehow I fear the current strategy will just see more cases of cancer and more deaths whatever spin is put on it. And I haven’t even talked about whether the country can afford it or not!

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Cancer becoming an ever younger disease

New data, which makes a mockery of officialdom´s view that cancer is an old person´s disease with rates rising in line with an aging population, has emerged.

The risk of developing cancer in your middle age has now risen by more than a third since 1980. Breast cancer rates increased by 50 per cent. And prostate cancer rates grew a whopping 6 fold in middle aged men! (Ed: As usual, the report from Cancer Research UK, bumbles on about better screening, lifestyle factors such as obesity, and promises more and better treatments. Why is it only CANCERactive that talks about the significant environmental causes of cancer and the need for the precautionary principle to be adopted by Government and Health bodies alike? We want a more rigorous control on known carcinogens at state level – from BPA to formaldehyde – in everyday products, proper warnings on labels and real cancer prevention education. This study comes at the same time other experts are warning that the cost of treatments will become untenable. The UK cancer programme continues to look in the wrong direction. Where, oh where, is there a serious concern over cancer prevention.  Ultimately, our children will be the biggest losers.)  CANCERactive, Britain’s Number 1 Cancer Prevention web site, CLICK HERE

http://www.canceractive.com/index.aspx

http://www.canceractive.com/cancer-active-page-link.aspx?n=715&Title=Cancer Prevention Main Features

 

 

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