Thursday, December 8, 2011

Does salt really cause cancer?

A new report on cancer incidence and mortality in the UK, described on the Guardian website, suggests that 40% of cancers in women and 45% in men are preventable, due to lifestyle choices. This is great news for people pushing healthy diets and exercise (perhaps not such great news for those pushing genetic causation).
Dr Rachel Thompson, deputy head of science for the World Cancer Research Fund, said: "This adds to the now overwhelmingly strong evidence that our cancer risk is affected by our lifestyles.
"We hope this study helps to raise awareness of the fact that cancer is not simply a question of fate and that people can make changes today that can reduce their risk of developing cancer in the future. 
So, what is this overwhelmingly strong evidence? The authors chose 14 different risk factors, as listed in the table below (taken from the paper).

Table 1. Exposures considered, and theoretical optimum exposure level
            Exposure                             Optimum exposure
Tobacco smoke                                                 Nil
Alcohol consumption                                       Nil
1.      Deficit in intake of fruit and veg        ≥5 servings (400 g) per day
2.      Red and preserved meat                     Nil
3.      Deficit in intake of dietary fiber        ≥23 g per day
4.      Excess intake of salt                             ≤6 g per day
Overweight and obesity                                BMI ≤25 kb m-2
Physical exercise                                            ≥30 min 5 times per week
Exogenous hormones                                    Nil
Infections                                                         Nil
Radiation – ionizing                                      Nil
Radiation – solar (UV)                                 As in 1903 birth cohort
Occupational exposures                               Nil
Reproduction: breast feeding                      Min of 6 months

The study calculated the "population attributable fraction" of each risk factor, that is, how much excess cancer was due to exposure to the risk factor. They compared cancer incidence in those exposed with incidence in those not exposed and assumed any excess (or, in theory, deficit) was due to the risk factor.

They chose risk factors based on the following criteria:
1. There was sufficient evidence on the presence and magnitude of likely causal associations with cancer risk from high-quality epidemiological studies.
2. Data on risk factor exposure were available from nationally representative surveys.
3. There were achievable alternative exposure levels that would modify the risk.

They calculated the relative risk per unit of exposure for cancers with probable or convincing causal associations with each risk factor, based on observational epidemiological studies. These would be the same studies you see reported in the news every day, telling you that you should or shouldn't eat butter, should or shouldn't go out into the sun, should or shouldn't eat sugar.

But there is something rotten in the state of Denmark, because despite billions of dollars, hundreds of thousands of study subjects, countless studies over decades of time by the most prominent (or, that is, highly placed) epidemiologists, the actual truth about the data is very different, surprising as that may seem. Indeed, as far as we know, the only truly convincing risk factors in this list are tobacco, papilloma virus and radiation, and even there it isn't really clear how much radiation exposure is too much (and many would say no exposure is the only completely safe exposure, though some exposures may detect treatable dangerous conditions and be good in the net).

The other behavioral risk factors have been shown in some studies to account for a small fraction of risk, though the results aren't always replicable. Indeed we can assert what we've just said because, by chance we just heard a talk by Gary Taubes, a science journalist for the New York Times and Science, among other outlets, who has systematically been debunking the idea that low fat diets have been shown definitively to prevent heart disease and cancer. He says the data just aren't there and never have been, but that it's been a belief so entrenched that it can't be denied because of all the vested interest that would challenge.

Hey, we like a good heretic as much as the next guy. And Taubes has written some of the best stuff out there on why observational epidemiology can't answer basic questions about cause and effect (here and here, for example). His work on dietary fat is very convincing, and his more general point that observational epidemiology can't be the basis for dietary recommendations is equally convincing. (So it's confusing that he's now a strong advocate for the idea that processed sugar is toxic, and responsible for the obesity and diabetes epidemics all over the globe -- conclusions largely based on the same kinds of observational studies he debunks when it comes to risk factors he doesn't like.)

But we digress. We are more than willing to accept that environmental risk factors can lead to disease. If not, only genetic variation would cause disease, and that clearly isn't so! We write about this all the time on MT. We just aren't nearly as ready to accept that we know definitively what those risk factors and their associated risks are. Nor that everyone is equally at risk from every factor.

Some of the optimal exposure levels in the list probably come under the category of 'wouldn't hurt', but public health measures are, by design, meant to be population-based, and the economic costs of encouraging lifestyle changes on a population level are not trivial. Nor is the cost of lost credibility when the risk factors turn out to be less important than we've been told after all.

Worse, risk is always and necessarily estimated retrospectively by relating outcomes quantitatively to exposure histories. But what we want to know is the future risk, and we know very well that we cannot predict the mix or amount of exposures to who-knows-what risk factors in the future. This is a deeply troubling problem, since major changes in risk for many or even most complex disease have occurred, often because of unclear behaviors or exposures, just in the past 50 years or so.

So, here's the safest conclusion to date -- do (most) everything in moderation, and don't worry about it. Something will get you in the end, so try to have the best time you can before that.

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