Tag

• Cancer results when stem cells divide and mutate uncontrollably
• Whether this is predominantly the result of intrinsic or extrinsic factors is unclear
• Some experts say 65% of cancers result from intrinsic factors and are unavoidable
• Other experts say most cancers result from extrinsic factors and are avoidable
• Cancer strategy should not hide behind ‘bad luck’
• Resources need to be allocated more smartly to prevent cancer

Is cancer the result of bad luck and unavoidable, or is it self-inflicted and prevented by simple lifestyles choices? Two 2015 studies arrive at strikingly different conclusions.
 
One, carried out by researchers from the John Hopkins Kimmel Cancer Centre and published in January 2015 in the journal Science, suggests that two thirds of cancers result from bad luck. Another, carried out by researchers from the Stony Brook Cancer Centre in New York and published in December 2015 in the journal Nature rebuts the findings of the Science paper, and suggests that 70 to 90% of cancer risk is self-inflicted and therefore can be avoided.

Which is right? And, why should this concern us?
 

Cancer

Cancer is a complex group of diseases characterised by the uncontrolled growth and spread of abnormal cells. If this is not checked it can cause death. Nearly 80% of all cancer diagnoses are in people aged 55 or older. Some facts about cancer In 2015 around 1.7m new cancer cases were diagnosed in the US, and about 330,000 in the UK. Each year, there are some 589,430 cancer deaths in the US, and some 162,000 in the UK. The annual treatment cost of cancer for the US is about $90bn and for the UK about £10bn. The causes of cancer include genetic, and lifestyle factors; certain types of infections; and environmental exposures to different types of chemicals and radiation.  Whitfield Growdon, Oncology Surgeon at Massachusetts General Hospital and professor at the Harvard University Medical School describes cancer and the causes of cancer.


         

The Science paper: cancer is unavoidable

The Science paper found that 65% of cancer cases are a result of bad luck: random DNA mutations in tissue cells during the ordinary process of stem cell division; regardless of lifestyle and hereditary factors. The remaining 35% of cancer cases, say the authors, are caused by a combination of similar mutations and some environmental and hereditary factors. One implication of these findings is that preventative strategies will not make a significant difference to the incidence rates of most adult cancers. So accordingly, the optimal way to reduce adult cancers is early detection when they are still curable by surgery.
 
Stem cell division is the normal process of cell renewal, but the extent to which random cell mutations contribute to cancer incidence, compared with hereditary or environmental factors, is not altogether clear. This is what the John Hopkins researchers sought to address with their study. Scientists examined 31 tissue types to discover whether the sheer number of cell divisions increases the number of DNA mutations, and therefore make a given tissue more prone to become cancerous.
 
Researchers developed a mathematical model, which suggested that it is incorrect to assume that cancer may be prevented with “good genes” even though we smoke, drink heavily, and carry excess weight. Their study found that, "the majority [of adult cancer risk] is due to bad luck, that is, random mutations arising during DNA replication in normal, noncancerous stem cells."  And, "this is important not only for understanding the disease, but also for designing strategies to limit the mortality it causes," say the researchers.
 
According to the Science paper bad luck mutations account for 22 of 31 adult cancer types, including ovarian, pancreatic, bone and testicular cancers. The remaining nine, including lung, skin and colorectal cancers, occurred more often than the random mutation rate predicted. This suggests that in these cancers, either inherited genes or environmental factors have a significant influence on cases.
 
“Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” says Bert Vogelstein, Clayton Professor of Oncology at the John Hopkins University School of Medicine, and co-author of the study. One example, he says, is in colon tissue, which in humans, undergoes four times more stem cell divisions than small intestine tissue. Likewise, colon cancer is much more prevalent than small intestinal cancer.
 
In a BBC Radio 4 interview Cristian Tomasetti, co-author of the study said: “Let’s say my parents smoked all their lives, and they never got lung cancer. If I strongly believed cancer was only environment, or the genes that are inherited, then since my parents didn’t get cancer, I may think I must have good genes, and it would be OK to for me to smoke. On the contrary, our study says ‘no’, my parents were just extremely lucky, and played a very dangerous game.”

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The Nature paper: cancer is avoidable

In a BBC interview, Yusuf Hannun, Director of the Stony Brook Cancer Center, Joel Strum Kenny Professor of Cancer Research and one of the authors of the Nature paper, challenged the findings of the ‘bad luck’ study. He suggests that hiding behind ‘bad luck’ is like playing Russian roulette with one bullet; one in six will get cancer. "What a smoker does is add two or three more bullets to the revolver and pulls the trigger. Although there is still an element of luck, because not every smoker gets cancer, they have stacked the odds against themselves. From a public health point of view, we want to remove as many bullets as possible from the revolver," says Hannun.
 
The Nature paper rebuts the John Hopkins ‘bad luck’ thesis. Its lead author, Song Wu, from the Department of Applied Mathematics and Statistics at Stony Brook University, notes that the Science paper had not conducted an alternative analysis to determine the extent to which external risk factors contribute to cancer development, and it assumes that the two variables: intrinsic stem-cell division rates, and extrinsic factors, are independent. “But what if environmental factors affect stem-cell division rates, as radiation is known to do?” asks Wu.
 
Wu and his colleagues provide an alternative analysis by applying four analytical approaches to the data that were used in the earlier Science paper and arrive at a radically different conclusion: that 70 to 90% of adult cancer cases result from environmental and lifestyle factors, such as smoking, drinking alcohol, sun exposure and air pollution. Wu admits that some rare cancers can result from genetic mutations, but suggest that incidence rates of cancers are far too high to be explained primarily by mutations in cell division.
 
According to the Nature paper, if intrinsic risk factors did play a key role in cancer development, the total number of divisions in tissue stem cells would correlate with lifetime cancer risk, and the incidence rates of the disease would be less than it actually is. Wu and his colleagues analyzed the same 31 cancer types as in the earlier Science paper, and evaluated the number of stem cell divisions in each. They then compared these rates with lifetime cancer incidence among the same cancer types. This allowed them to calculate the contribution of stem cell division to cancer risk.
 
Wu et al also pursued epidemiological evidence to further access the contribution of environmental factors to cancer risk. They analyzed previous cancer studies, which show how immigrants moving from regions of low cancer incidence to regions with high cancer incidence soon develop the same tumor rates, suggesting that the risks are environmental rather than biological or genetic.
 
The researchers’ findings suggest that mutations during cell division rarely accumulate to the point of producing cancer, even in tissues with relatively high rates of cell division. In almost all cases, the Nature paper found that some exposure to carcinogens or other environmental factors would be needed to trigger disease, which again suggested that the risks of the most prevalent adult cancers are due to environmental factors. For example, 75% of the risk of colorectal cancer is due to diet, 86% per cent of the risk of skin cancer is due to sun exposure, and 75% of the risk of developing head and neck cancers is due to tobacco and alcohol.
 
The Nature paper concludes that bad luck, or intrinsic factors, only explain 10 to 30% of cancer cases, while 70 to 90% of adult cancer cases result from environmental and lifestyle factors. "Irrespective of whether a subpopulation or all dividing cells contribute to cancer, these results indicate that intrinsic factors do not play a major causal role," say the authors. This suggests that many adult cancers may be more preventable than previously thought. 
 

Preventing cancer 

Even the Science study concedes that extrinsic factors play a role in 35% of the most common adult cancers, including lung, skin and colorectal cancers. This, together with the Nature study, and the rising incidence of avoidable cancers, should be a wake-up call because a substantial proportion of cancers can be prevented.
 
Hannun is right! Whatever the causes of cancer, we should not ‘hide behind bad luck’.  We should act on evidence, which suggests that it is within everyone’s capabilities to make simple lifestyle changes that can prevent common adult cancers.  Although maintaining a healthy lifestyle is no guarantee of not getting cancer, the Nature paper underlines the fact that a healthy lifestyle stacks the odds in your favor.  The paper supports preventative cancer strategies.
 
In 2015, tobacco smoking caused about 171,000 of the estimated 589,430 cancer deaths in the US. The Nature paper suggests that the overwhelming majority of these could have been prevented. In addition, the World Cancer Research Fund has estimated that up to 33% of the cancer cases that occur in developed countries are related to being overweight or to obesity, physical inactivity, and/or poor nutrition, and thus could also be prevented.
 
It seems reasonable to suggest that the risk of cancer can be significantly reduced by: (i) a cessation of smoking, (ii) drinking less alcohol, (iii) protecting your skin from the sun, (iv) eating healthily, (v) maintaining a healthy weight, and (vi) exercising regularly.
 

The UK Position

Everyone understands the enormity of the burden of cancer, and what to do to reduce its risk. In the UK, as in other wealthy countries, there is no lack of money, no lack of resources, and no lack of expertise for cancer care. The annual spend on cancer diagnosis and treatment alone in the UK is about £10 billion. The UK also has a government appointed Cancer Czar charged with producing a national cancer plan to bring Britain's cancer survival rates up to those of European levels. Despite our understanding and all these resources, a 2014 study published in the Lancet suggests that cancer survival rates in the UK still lag more than 20 years behind many other European countries, and that people are dying needlessly.  Why is this?
 

Fear of preventative medicine 

Writing in The Times in January 2016, Sir Liam Donaldson, a former UK Chief Medical Officer, suggested that although preventative healthcare strategies are vital “to provide safe, high quality care without running out of money”, governments avoid helping the public to mitigate the risks of modern living, which can cause cancer, because of  “two primal political forces: the mortal dread of being labeled a ‘nanny state’, and a fear of removing people’s perceived pleasures.”
 
During Donaldson’s tenure between 1998 and 2010, the government rejected his recommendation for a minimum unit price for alcohol, and for the same reasons in 2014, the government rejected a tax on sugar recommended by Public Health England. Excess sugar increases the risk of cancer, heart disease and diabetes. According to Donaldson, without effective government action to lower the vast and escalating burden of cancer, and other chronic diseases, the NHS is unsustainable.
 
The missing link in preventative strategies is behavioral techniques that engage people who are at risk and help them change their behaviors. Such techniques have been demonstrated to be successful in both the UK and US. They explain how people behave, and encourage them to reduce unhelpful influences on their health, and change the way they think and act about important health-related issues such as diets, lifestyles, screenings and medication-management. See: Behavioral Science provides the key to reducing diabetes
 

Takeaway 

It is crucial that the UK government now embraces behavioral techniques to curb the curse of cancer.  Donaldson is right: if cancer, and other chronic diseases, which together consume the overwhelming percentage of healthcare expenditure, are not prevented the NHS will become unsustainable.

Diabetes wars

• Failing diabetes services are waisting money
• Too many people with diabetes develop avoidable complications
• No one is held accountable for poor diabetes service performance
• The NHS payment systems do not effectively incentivise the delivery of recommended standards of diabetes care
• Appropriate incentives for diabetes services could improve diabetes outcomes and save the HNS £170m per year

National Audit Office v. NHS

A war is being waged between the NHS and the UK’s National Audit Office (NAO) over the state of adult diabetes services in the UK. Two NAO reviews found that doctors are failing to meet nationally agreed standards of diabetes care, and that they are neither effectively incentivised to deliver and sustain quality services nor accountable for poor service. 

The NHS says it is committed to supporting doctors to deliver high-quality care to people with and at risk of diabetes, but the NAO is not convinced.  It recommends that monies for diabetes services and doctors’ remuneration should be linked more directly to desired patient outcomes in order to promote and sustain accountability, responsibility, learning and the strengthening of local capacity. 

 

Adult or type 2 diabetes (T2DM) is an avoidable chronic condition, which occurs when the body does not produce enough insulin to function properly, or the body’s cells do not react to insulin. This means that glucose stays in the blood, and is not used as fuel for energy. There are currently 3.9 million people living with diabetes in the UK, with 90% of those affected having T2DM. Diabetes is a cause of serious long-term health problems, which include blindness, kidney failure, lower limb amputation, and cardiovascular disease, such as a stroke. Roni Sharvana Saha, Consultant in Acute Medicine, Diabetes and Endocrinology at St Georges University Hospital, London describes why weight control is important for the management of T2DM.

         
            (click on the image to play the video) 

Local responsibility for adult diabetes services 

In England the responsibility for diabetes services and support rests with local Clinical Commissioning Groups (CCGs) and GPs. In 2003 the UK government gave primary care trusts the responsibility for commissioning local services on behalf of their local populations, and freedom to decide how to best deliver diabetes services. It is for GP practices to ensure that people with diabetes receive all the nine recommended care processes each year in accordance with agreed clinical guidance (see below). In 2004 the Quality and Outcomes Framework (QOF) was introduced as part of the new GP contract, which includes payments for undertaking specified clinical activities and achieving set clinical indicators.

 

The nine basic processes of diabetes care are: (i) blood glucose level measurement (HbA1c), (ii) blood pressure measurement, (iii) cholesterol level measurement, (iv) retinal screening, (v) foot and leg check, (vi) kidney function testing (urine),  (vii) kidney function testing (blood), (viii) weight check, (ix) smoking status check.
 

Failing incentives

QOF awards for GPs initially improved diabetes outcomes in primary care. However, recently there has been little improvement, and according to the NAO the current payment system for GPs is not driving the required patient outcomes. GPs are paid for each individual diabetes test they carry out rather than being rewarded for ensuring that all nine tests are delivered. Similarly, the Payment by Results tariff system for English hospitals does not incentivize the multi-disciplinary care required to treat a complex long-term condition such as diabetes. According to the NAO the NHS needs to review and enhance its payment systems to ensure that they effectively incentivise good care and better outcomes for people with diabetes.
 

National Audit Office’s First Review (2012)

In May 2012 the NAO’s first review of adult diabetes services in England found that the NHS was not delivering value for money, and that it was underestimating its annual spend on diabetes services by some £2.6 billion. “There is poor performance in expected levels of diabetes care, low achievement of treatment standards, and 24,000 people die each year from avoidable causes relating to diabetes”, said the report.

The NAO findings included the following:

    1. "Fewer than one in five people with diabetes in England are being treated to recommended standards, which reduce their risk of diabetes-related complications
    2. Many people with diabetes develop avoidable complications
    3. NHS accountability structures fail to hold commissioners of diabetes service providers to account for poor performance
    4. No one is held accountable for poor performance, despite the fact that performance data exist
    5. The NHS is not effectively incentivising the delivery of all aspects of recommended standards of care through the payments systems
    6. There is a lack of clarity about the most effective way to deliver diabetes services
    7. Payment mechanisms available to GPs are failing to ensure sustained improvements in outcomes for people with diabetes
    8. The NHS does not clearly understand the costs of diabetes
    9. Effective management of diabetes-related complications could save the NHS £170 million a year"

The NAO Recommendation

The NAO recommended that the system of incentives for doctors be renegotiated to improve outcomes for people with diabetes in accordance with agreed clinical practice. GPs should only be paid for diabetes care if they ensure all nine care processes are delivered to people with diabetes. Also the NAO recommended that the thresholds at which GPs are remunerated for achieving treatment standards should be reviewed regularly.
 

Public Accounts Committee Chair: “Depressing report”

Margaret Hodge, chair of The House of Commons Committee on Public Accounts, which took oral and written evidence on the NAO Report, said, “This was one of the most depressing Reports I’ve read. Everybody understands the enormity of the problem; nobody is arguing with the figures; everybody accepts both the nature of the checks, and the treatments to prevent complications that should be done; money or lack of it has not been an issue; there appears to be a structure within the Department of Health with a tsar and a group of people whose job it is—and yet we are failing.”
 

Public Accounts Committee’s Conclusion: Higher costs, poorer services

The conclusions of Public Accounts Committee echoed its chair’s opening remarks, “Although there is consensus about what needs to be done for people with diabetes, progress in delivering the recommended standards of care and in achieving treatment targets has been depressingly poor. There is no strong national leadership, no effective accountability arrangements for commissioners, and no appropriate performance incentives for providers. We have seen no evidence that the Department of Health will ensure that these issues are addressed effectively . . . . Failure by it to do so will lead to higher costs to the NHS as well as less than adequate support for people with diabetes.”
 

Action for Diabetes: the NHS’s Defence (2014)

In January 2014 the NHS defended its services in Action for Diabetes, a report prepared by its Medical Directorate, which sets out the activities NHS England is undertaking as a direct commissioner of GP and other primary care services, and as a support to secondary and community care commissioners to improve outcomes for people with and at risk of diabetes. The report stated that between 1996 and 2002 there was a, “marked reduction in excess mortality in those with diabetes”, and the UK’s diabetes-related mortality rates were better than 19 other developed economies. 

Action for Diabetes reaffirmed that the NHS was committed to supporting CCGs to deliver high-quality care to people with and at risk of diabetes, and will:

      • “Provide tools and resources to support commissioners in driving quality improvement
      • Ensure robust and transparent outcomes information, and align levers and incentives to facilitate delivery of integrated care across provider institutional boundaries
      • Empower patients with information to support their choices about their own health and care, and support the development of IT solutions that allow sharing of information between providers and between providers and people with diabetes
      • Look to the future of the NHS to deliver continued improved outcomes for people with or at risk of diabetes.” 

In a foreword to Action for Diabetes Professor Jonathan Valabhji, the UK government’s National Clinical Director for Obesity and Diabetes, said the NHS needs, “new thinking about how to provide integrated (diabetes) services in the future in order to give individuals the care and support they require in the most efficient and appropriate care settings, across primary, community, secondary, mental health and social care, and in a safe timescale”.
 

National Audit Office’s Second Review (2015) 

In October 2015, the NAO published a follow-up review of NHS adult diabetes services, and criticised (I) the still low rates of the delivery of basic diabetes care processes, and (ii) the low rates of attainment of diabetes treatment goals. The NAO pointed to the escalation of avoidable complications, such as amputation, blindness, kidney failure and stroke that consume about 70% of the annual treatment costs of the NHS on diabetes.  The report commented:  “The improvements in the delivery of key care processes have stalled, . . . and this is likely to be reflected in a halt to outcomes improvement for diabetes patients . . . There are still 22,000 people estimated to be dying each year from diabetes-related causes that could potentially be avoidable”.

Ineffective payment systems

The NAO’s 2015 report criticized the way that the NHS distributes money, and sets local incentives for improving the delivery diabetes services. Economists have long argued that bureaucrats distributing monies with loose conditions is not an effective way to achieve transformative change. According to the NAO, “Current financial incentives, funding mechanisms and organisational structures of health services do not support the delivery of integrated diabetes care”. The NAO recommends that the NHS should, “Ensure that its payment systems effectively incentivise good care and better outcomes for people with diabetes”. 

Comment: Reasons for failure

According to market economists aid is at best wasteful, and at worst creates a damaging culture of dependency. Also, aid is often subject to vested interests, and fails to change people’s behaviors and improve wellbeing.
 
Institutions responsible for delivering diabetes services in England have not learned these lessons, and as a consequence poorly incentivized diabetes service providers fail to propel people living with diabetes towards self-management, and fail to slow the onset of devastating and costly complications. 
 

Effective incentives are key for improving diabetes outcomes

This Commentary has suggested that without appropriate incentives diabetes service providers have become chronically dependent on their paymasters, which has stifled innovation, made service providers less focused on patient outcomes, and less likely to innovate and prioritize the generation of other resources. Current incentives for diabetes service providers should be renegotiated.
 
A previous Commentary suggested that effective patient outcomes occur when people and communities are engaged and assume greater responsibility for their own wellbeing. Tried and tested behavioral techniques successfully used by the Cameron and Obama administrations need to be embedded in a range of diabetes services to create offerings that people want and that actually lower the risk of T2DM, propel those living with the condition into self-management, and slow the onset of devastating and costly complications; see Behavioral Science provides the key to reducing diabetes.
 
A related issue, which needs to be addressed to improve patient outcomes further, is the need to reduce the power of the bureaucracies that control the provision of diabetes services and to increase competition among diabetes service providers. Current bureaucratic diabetes service providers present a significant barrier for new entrants, and thereby discourage investments in innovations and new technologies. This will be the subject of a future Commentary.