A Health & Environment retrospective: concerns that talking about causes of cancer can cause cancer; the difficulties of defining “endocrine disruptor”; shedding light on the obesogen hypothesis; and more.August 14, 2013 at 4:09 pm | Posted in H&E Features | Leave a comment
Tags: BPA, Cancer, chemicals, endocrine disruptor, environment, health, PFCs, science, thresholds of toxicological concern, triclosan
After 5 years and 60 editions of Health & Environment, we look back at our most popular articles.
Does discussion of environmental causes of cancer cause cancer? There is no obvious reason why the 2010 US President’s Cancer Panel examination of chemicals as potential, under-discussed causes of cancer should have caused so much controversy. The report was hardly unheralded while the recommendations were in line with much existing cancer prevention strategy. The conclusion that one is forced to, is critics of the report must believe that discussing environmental causes of cancer undermines cancer prevention strategy: in other words, that talk about environmental causes of cancer causes cancer. (July 2012)
False alarms or missed hazards: how should regulators define “endocrine disruptor”? The trade-offs entailed in how we define, for regulatory purposes, a chemical as an endocrine disruptor should make us very cautious about conflating the purpose of a regulatory definition of EDC with the purpose of a scientifically correct definition of EDC, and may even show us that the process of defining EDC is a democratic matter which cannot be decided by expert committees alone. (November 2012)
Even though BPA is a weak oestrogen, there is a mechanism by which low levels of BPA could have a powerful health effect. It is often argued that BPA is too weak a hormone to have an effect on cell function. Here, we sketch out a mechanism by which BPA could potentially have a strong effect via an indirect pathway rather than a direct effect on the part of the cell nucleus which responds to oestrogen. (July 2009)
Thresholds of Toxicological Concern: Evaluating an Initiative to Reduce Animal Testing. One rationale for reducing the burden of chemical toxicity testing is the application of thresholds of toxicological concern (TTCs), a pragmatic, probabilistic approach to risk assessment of substances for which toxicity data are unavailable. It holds that if a substance is unlikely enough to pose a risk to health, then toxicological testing of the substance is not required. (January 2012)
The Obesogen Hypothesis. Energy imbalance is the immediate cause of obesity, a combination of excess dietary calories and a lack of physical activity. However, the full set of reasons as to control over energy balance can be lost is complex – and it is now being hypothesised that chemical pollutants have a role to play. (March 2011)
Shifting the curve: how small changes in individuals have large effects in populations. “Shifting the Curve,” a video narrated by Dr. Bruce Lanphear of Simon Fraser University, shows graphically how small effects – like an increase in the number of individual children with ADHD-related behaviors – result in large increases in the prevalence of ADHD in the overall population. (October 2012)
Assessing Risk Posed by Chemicals in Mixtures. Current practice in risk assessment, although changing, is more-or-less grounded in the 1970s, when pollution from industrial smokestacks and waste outlets was seen as the primary source of risk. It is now recognised that people are exposed to a wide variety of chemicals from many sources, not just industrial pollution. Rather than anticipating the risk to health and the environment posed by a specific waste outflow, the problem has become one of understanding and managing the risk that multiple, everyday exposures may pose to health. (July 2011)
PFCs: A case study in favour of the precautionary principle. PFCs are an example of how production and marketing of a substance can outpace scientific research into its safety and placing regulatory restrictions on its use. In the case of PFCs, this has resulted in 3 generations of people being exposed to an unknown hazard while a complex consensus, based on weak data and economic interests, develops around restricting their use. (December 2011)
Triclosan or soap and water? Despite its widespread use, only a relatively small amount of research into the potential health effects of triclosan has been published. Much of the evidence for potential harm from triclosan comes from in vivo amphibian and fish studies and in vitro mammalian studies. (March 2013)
Tags: Cancer, cancer prevention, environment, female cancers, health, medicine, public health
Cancer prevention strategies are based on what is known about attributable causes of cancer. But does focusing on existing knowledge advance or hamper efforts to reduce cancer incidence? We evaluate two opposing perspectives to conclude that demanding highly robust data may in fact limit our ability to prevent cancers beyond the proportion caused by lifestyle choices.
In December, the British Journal of Cancer published an analysis of the fraction of cancers in the UK in 2010 which were attributable to lifestyle and environmental factors (Parkin 2011). Among the main findings were that 23% of male and 15% of female cancers were caused by tobacco use, that alcohol consumption was responsible for 3-5% of cancers in both males and females, and that obesity was responsible for 6% of female cancers [chart here].
Casual readers may be puzzled by two features of the report: firstly, although the report states it is about environmental causes of cancer, it deals almost exclusively with lifestyle choices; and secondly, although the report only identifies causes for 40% of cancers, it makes a clear statement that these factors ought to be prioritised as part of a cancer prevention programme.
Why so little discussion of the environment?
Lay readers (not epidemiologists) are likely to understand the term “environmental” as referring to anything with which the body involuntarily interacts with in the world, in particular pollutants, while lifestyle factors are likely to be interpreted as encompassing people’s choices, such as what they eat and how much they exercise.
There is a simple explanation as to why the report equates environmental causes of cancer with lifestyle causes, as Professor Max Parkin, lead author of the BJC report, explains: “Epidemiologists just split things up into environmental or genetic. Genetic is something built in from the word go, that you are born with. Everything else is an external influence, which is referred to as environmental.”
Of course, what many environmental organisations are interested in is the specific contribution which inadvertent exposure to environmental pollutants makes to the burden of cancer and other disease. On this, the report has very little to say, devoting only one chapter to occupational causes of cancer, and no space at all to environmental pollutants and chemicals as a potential cause of cancer.
Instead, the BJC report satisfies itself with identifying lifestyle causes of cancer and leaving the causes of the other 60% of cancers unaccounted for. Since most lifestyle factors are accounted for in the study, this leaves a significant proportion which must be environmental in the conventional sense. So why are they not in the report?
There is a simple explanation for this as well: there are no specific environmental causes of cancer for which there are sufficient data to calculate attributable risk. For calculating attributable risk, the BJC report required sufficient evidence on the presence and magnitude of likely causal associations with cancer risk from high-quality epidemiological studies, and data on risk factor exposure from nationally representative surveys.
“We could have written a little bit about air pollution,” says Parkin. “However, it is likely to be a minor component compared to those other things [assessed in the report]. It could be doubling the risk of cancer, but we don’t really have a very good hold on that.”
“It’s possible there are things we don’t know about which are substantial contributors to cancer,” Parkin adds. “But never say never: 35 years ago we didn’t know about HPV [human papilloma virus, a major risk factor in cervical cancer] so there might be something out there. It’s a bit odd that non-Hodgkin’s lymphoma is going up, and testicular cancer likewise. However, it is unlikely we will find [another major factor] like smoking.”
If only 40% of cancers are accounted for, why are these the most important causes to address?
The BJC figures are clearly intended to inform the UK’s cancer prevention strategy and place the emphasis on people’s choices about diet, exercise, alcohol consumption and so forth. Cancer Research UK’s Chief Executive, Dr Harpal Kumar, describes these “healthy habits” as the priority for cancer prevention (CRUK 2011). Tobacco cessation therefore continues to be the number-one priority, with reducing alcohol intake and encouraging more exercise and better diet next in the queue.
Some argue this approach does more harm than good. Professors Andrew Watterson and Rory O’Neill of the University of Stirling, Scotland, argue forcefully against the “victim-blaming” they see as implicit in a healthy habits strategy, diverts attention away from the broader, societal roots of many cases of cancer, in which “income and social class connect directly to […] poor diet […] poor housing near busy, polluting roads and […] dusty, dirty, chemical-laden jobs and long hours” play into cancer incidence.
Not everybody sees things this way, however. In a Personal View in March’s Lancet Oncology, Professor Bernard Stewart of the University of New South Wales, Australia, acknowledges that although a focus on lifestyle does not recognise the burden caused by the chemical industry and associated pollution, no intervention based around reducing involuntary exposure to pollutants (except for air pollution) should be prioritised over lifestyle choices in a cancer prevention strategy (Stewart 2012).
Stewart argues that public health strategies aimed at cancer prevention have to be based in solid data. To be solid enough, the data has to show (1) the circumstances of exposure; (2) a calculation the consequential risk of cancer; and (3) the effectiveness of measures in reducing that risk of cancer. Only if all three boxes are ticked can an intervention be properly described as preventive.
For Stewart, only air pollution has adequate data for describing exposure and establishing the burden of cancer. He describes industrial pollution and pesticide findings as “not unequivocal”. For EDCs, their role in human breast cancer is “mainly inferential” and as yet unsupported by epidemiological evidence. Nor, he says, is there any evidence that there is a case of cancer which would have been avoided had a consumer decided not to buy a particular product, or had regulators been more diligent.
This is the interpretation of the data on which the established view that personal choices provide the greatest opportunities for reducing cancer incidence, while controls on specific pollutants are understood to be individually so causally insignificant they cannot be interpreted as part of a cancer prevention strategy.
Does this lead to an effective prevention strategy?
Professor Richard Clapp of Boston (US) University’s School of Public Health is unimpressed with the findings of the BJC report and is opposed to the view that lifestyle choices should be a priority in a cancer prevention strategy. Although Professor Richard Peto says the BJC report will focus attention on the high priority areas, such as refocusing on tobacco and the continuing importance of tobacco control and efforts to change the UK diet (Peto 2011), to Clapp, this is “just more of the same”.
“The 60% unknown is the elephant in the room,” says Clapp, reiterating Parkin’s and Stewart’s view that, beyond obvious causes such as smoking, it is very difficult to attribute percentages to causes of cancer. However, he draws a very different conclusion, saying it is “counterproductive and pointless” to assign certain exposures as causing a specific fraction of cancer when it is clear that preventable occupational and environmental exposure fuel excess cancer cases and deaths. (See e.g. Clapp et al. 2007)
Clapp argues this is because the fundamental mechanism of cancer is both environmental and genetic. Exposures from outside the body combine with inherited genes and genetic mutations, all of which converge to produce cancer. Overall, there are six essential alterations which need to happen in order for the body’s defences against cancer to be overwhelmed (Hanahan & Weinberg 2011).
Clapp describes this as an integrated circuit, in which a combination of exposures is required to produce a tumour, then prevention of any one of these will prevent the tumour. While preventing any of the single major factors, such as a carcinogenic exposure, is therefore a preventive measure, it becomes impossible to calculate what proportion of cancers any particular such measure prevents.
That the effectiveness of an intervention cannot be measured is unimportant for Clapp, who says we do not need a hierarchy of interventions or to play one cause off against another; exposures from all sources should be systematically reduced: “It doesn’t matter if tobacco is responsible for 20% or 30% of cancers; if it’s a carcinogen, we should minimise the exposure.”
Is Stewart’s position of holding out on action until the data is certain help set the right priorities for a cancer strategy, or does it limit our ability to prevent cancer?
For one thing, human exposure to chemicals is uncontrolled. In the instance we find a control group, exposure is usually so thoroughly confounded with other chemicals, lifestyle choices, occupation, economic status etc. that it becomes extremely difficult to prove an association which could pass as causal.
It is therefore hard to see how we can attain Stewart’s required level of proof for preventive action, beyond the 40% we already know about (and have known about for over 30 years). Waiting for proof for a set of factors which Stewart and Parkin both acknowledge may remain unproven for many years to come, seems a missed opportunity for preventing many cancers – even if we do not know how many cancers such action will prevent.
So although Stewart argues against use of the precautionary principle, it seems if we are to progress beyond the 40% of cancers attributed to lifestyle choices, we will ultimately have no choice but to work with limited data: being measurable is important, but only if your measurements help you make the optimal decision, rather than simply the optimal measurable decision.
“It is probable that limiting exposure to tobacco smoke has reduced incidence of lung cancer; there are lots of opportunities to expand that approach,” says Clapp. Watterson and O’Neill say that “social, political and physical environmental factors all play into cancer incidence and prevalence, and should form part of a coherent cancer prevention strategy.”
Although individual exposures are unlikely to make much difference to cancer risk, if there are hundreds of exposures which can be eliminated through general pollution control programmes, then significant further progress could be made. As Parkin acknowledges, “healthy habits” will not help the majority of people who don’t smoke, aren’t overweight and will get cancer anyway.
A lot of people working in environmental health, not least ourselves, were excited last year by an apparent move on the part of the International Agency for Research on Cancer (IARC) to start treating chemical contaminants in the environment as an important factor behind the disease.
Now we are waiting to see if this attitude shift translates into policy. Obviously this will take time, but the interview below with IARC head Professor Christopher Wild suggests they have some way to go, as he gives little evidence that IARC is giving consideration to chemical contaminants except in air pollution.
Q. What are the links between cancer and environment?
Professor Wild of the IARC quite rightly states that the majority of cancers have an environmental basis: we know this from the seminal study by Lichtenstein (2000) and a follow up study by his colleague, Czene (2002).
But Professor Wild then goes on to define the environment as a geneticist would, to include the likes of lifestyle, diet and occupation as well as the chemical contaminants which are the cause of much concern.
Using the ‘broad’ definition of the environment gives him the opportunity to talk about what we want on the public health agenda, i.e. cancer prevention.
However, the “prevention” he speaks of is in terms of lifestyle changes, diet, tobacco cessation and physical exercise. These measures are obviously very important and necessary, but shouldn’t be used to dodge talking about prevention of cancer by limiting involuntary exposures to carcinogens.
Professor Wild does in fact touch on environmental exposure to chemicals but seems to concentrate on air pollution and solid fuel exposure in homes, but doesn’t mention pesticides, EDCs or of involuntary exposure to these chemicals in consumer products and diet.
His language changes when comparing natural to anthropogenic exposures. He talks of “strong evidence” that aflatoxins and arsenic contaminated water is a factor in cancer. But then he only talks of “some” studies linking air pollution to human cancers.
Throughout his answer involuntary exposures to chemicals from human activities in the last 60 years was not addressed.
All the prevention measures he talks of in reply to the first question are based around exposures that are not involuntary (lifestyle) or are based on a problem where measures have been slowly put into practice i.e. air pollution, especially in Western countries.
Q. How IARC is researching these links especially with relation to cancer, environment, chemicals, life style etc.?
When asked about IARC’s research into environmental exposures and links to cancer, ‘specifically’ non-lifestyle exposures Professor Wild speaks about the IARC monographs program.
On the face of it the review of previously classified human/animal carcinogens is good to hear. However, when talking about research IARC carries out into cancer aetiology and factors which may be involved by bringing together laboratory studies and human epidemiology, again, he uses air pollution as an example.
Citing a large scale European study looking at the biological effects of ‘higher levels’ of air pollution. Here, Professor Wild did not take advantage of the opportunity to talk about chemical exposures or the effect that low levels of chemicals may have on health.
On a positive note, Professor Wild was interested in concerns that current toxicological tools are insufficient to measure real-world exposures, saying that more research is needed to monitor and measure exposures to “cocktail effects” in complex mixtures.