Saturday, January 21, 2012

Childhood Leukemia in France and Proximity to Nuclear Power Plants

This PDF reprint of an article published in the International Journal of Cancer, provides a glimpse onto the epidemiological battlefield for those laymen who wish to grapple with the ideas directly.

Childhood leukemia (CL) is one of a number of the tragic cancers of childhood. The cause of CL is not known, but CL has been studied in association with maternal age, birth weight, maternal alcohol intake, and most recently proximity to nuclear power plants (NPP).

Most previous studies -- including studies by an author of the study -- did not find an association between NPP proximity and CL rates.
In the authors' previous multisite incidence studies 29; 30 no association between proximity to NPPs and AL was observed. This was in line with most multisite studies 1; 2; 8; 12 , and is also in line with the results of the authors' incidence analysis over the whole period, 1990-2007

...Overall, the estimated doses due to NPPs were very low compared to the doses due to natural radiation sources. Such doses are not expected to result in an observable excess risk on the basis of the available evidence 41 _Study PDF
The authors introduced a new measure -- DBGZ (Dose Based Geographic Zoning) -- in an attempt to more precisely estimate the likely radioactive exposure to subjects due to the regulated release of radioactive materials from NPPs. Although the authors considered their new DBGZ metric to be a success, they failed to show any significant association between CL rates and their DBGZ metrics.

Let's go through the study in relationship with Hill's Criteria of Causation:

1. Temporal Relationship:

Exposure always precedes the outcome. If factor "A" is believed to cause a disease, then it is clear that factor "A" must necessarily always precede the occurrence of the disease. This is the only absolutely essential criterion. This criterion negates the validity of all functional explanations used in the social sciences, including the functionalist explanations that dominated British social anthropology for so many years and the ecological functionalism that pervades much American cultural ecology.

AF: Since the authors were looking at childhood leukemias for children 5 years and under, it is assumed that the nuclear power plants existed before the children were conceived.

2. Strength:

This is defined by the size of the association as measured by appropriate statistical tests. The stronger the association, the more likely it is that the relation of "A" to "B" is causal. For example, the more highly correlated hypertension is with a high sodium diet, the stronger is the relation between sodium and hypertension. Similarly, the higher the correlation between patrilocal residence and the practice of male circumcision, the stronger is the relation between the two social practices.

AF: The authors calculated an "odds ratio" of 1.9 and a "standardised incidence ratio" of 1.9, comparing the exposed to the non-exposed. This would be roughly interpreted as nearly double the risk of CL for children living within 5 km of a NPP. This association was only found for the 2002 through 2007 time span -- not for the full 1990 - 2007 period of the study.

It should be noted for comparison that the "odds ratio" for cigarettes and lung cancer has been calculated as close to 9 (PDF) in some studies, or a 9 X risk for smokers to get lung cancer as opposed to non-smokers.

3. Dose-Response Relationship:

An increasing amount of exposure increases the risk. If a dose-response relationship is present, it is strong evidence for a causal relationship. However, as with specificity (see below), the absence of a dose-response relationship does not rule out a causal relationship. A threshold may exist above which a relationship may develop. At the same time, if a specific factor is the cause of a disease, the incidence of the disease should decline when exposure to the factor is reduced or eliminated. An anthropological example of this would be the relationship between population growth and agricultural intensification. If population growth is a cause of agricultural intensification, then an increase in the size of a population within a given area should result in a commensurate increase in the amount of energy and resources invested in agricultural production. Conversely, when a population decrease occurs, we should see a commensurate reduction in the investment of energy and resources per acre. This is precisely what happened in Europe before and after the Black Plague. The same analogy can be applied to global temperatures. If increasing levels of CO2 in the atmosphere causes increasing global temperatures, then "other things being equal", we should see both a commensurate increase and a commensurate decrease in global temperatures following an increase or decrease respectively in CO2 levels in the atmosphere.

AF: The dose response measures used were either "distance from NPP" or "Dose Based Geographic Zone (DBGZ), a measure devised by the authors specifically for this study. This was an important failing of the study, since important information relating to "radiation dosing" related to distance was assumed and estimated, rather than carefully collected. Time period of exposure -- time at particular addresses etc. -- was likewise not collected, but rather estimated.

4. Consistency:

The association is consistent when results are replicated in studies in different settings using different methods. That is, if a relationship is causal, we would expect to find it consistently in different studies and among different populations. This is why numerous experiments have to be done before meaningful statements can be made about the causal relationship between two or more factors. For example, it required thousands of highly technical studies of the relationship between cigarette smoking and cancer before a definitive conclusion could be made that cigarette smoking increases the risk of (but does not cause) cancer. Similarly, it would require numerous studies of the difference between male and female performance of specific behaviors by a number of different researchers and under a variety of different circumstances before a conclusion could be made regarding whether a gender difference exists in the performance of such behaviors.

AF: As noted above, this study was inconsistent not only with similar studies by other authors, but also with previous studies by the same authors.

5. Plausibility:

The association agrees with currently accepted understanding of pathological processes. In other words, there needs to be some theoretical basis for positing an association between a vector and disease, or one social phenomenon and another. One may, by chance, discover a correlation between the price of bananas and the election of dog catchers in a particular community, but there is not likely to be any logical connection between the two phenomena. On the other hand, the discovery of a correlation between population growth and the incidence of warfare among Yanomamo villages would fit well with ecological theories of conflict under conditions of increasing competition over resources. At the same time, research that disagrees with established theory is not necessarily false; it may, in fact, force a reconsideration of accepted beliefs and principles.

AF: The authors admit that natural radiation exposures for subjects would almost certainly overwhelm any likely radiation exposures from proximity to the NPPs, according to known mechanisms of radiation exposure.

6. Consideration of Alternate Explanations:

In judging whether a reported association is causal, it is necessary to determine the extent to which researchers have taken other possible explanations into account and have effectively ruled out such alternate explanations. In other words, it is always necessary to consider multiple hypotheses before making conclusions about the causal relationship between any two items under investigation.

AF: The authors fail to provide alternate explanations for their findings.

7. Experiment:

The condition can be altered (prevented or ameliorated) by an appropriate experimental regimen.

AF: Experiments in this setting would be unethical. [More: A prohibition zone of 5 km around NPPs could be created, and subsequent rates of CL could be measured and compared with earlier rates. This would not be a valid experiment, but might satisfy a small subset of bureaucrats and/or activists.]

8. Specificity:

This is established when a single putative cause produces a specific effect. This is considered by some to be the weakest of all the criteria. The diseases attributed to cigarette smoking, for example, do not meet this criteria. When specificity of an association is found, it provides additional support for a causal relationship. However, absence of specificity in no way negates a causal relationship. Because outcomes (be they the spread of a disease, the incidence of a specific human social behavior or changes in global temperature) are likely to have multiple factors influencing them, it is highly unlikely that we will find a one-to-one cause-effect relationship between two phenomena. Causality is most often multiple. Therefore, it is necessary to examine specific causal relationships within a larger systemic perspective.

AF: Causes of acute childhood leukemias are poorly understood in general.

9. Coherence:

The association should be compatible with existing theory and knowledge. In other words, it is necessary to evaluate claims of causality within the context of the current state of knowledge within a given field and in related fields. What do we have to sacrifice about what we currently know in order to accept a particular claim of causality. What, for example, do we have to reject regarding our current knowledge in geography, physics, biology and anthropology in order to accept the Creationist claim that the world was created as described in the Bible a few thousand years ago? Similarly, how consistent are racist and sexist theories of intelligence with our current understanding of how genes work and how they are inherited from one generation to the next? However, as with the issue of plausibility, research that disagrees with established theory and knowledge are not automatically false. They may, in fact, force a reconsideration of accepted beliefs and principles. All currently accepted theories, including Evolution, Relativity and non-Malthusian population ecology, were at one time new ideas that challenged orthodoxy. Thomas Kuhn has referred to such changes in accepted theories as "Paradigm Shifts".

AF: The claimed association is not compatible with nor explainable by existing theory.

It should be pointed out that out of 2,753 cases of CL in France from 2002 to 2007, 14 cases were estimated to have occurred within 5 km of a NPP. Given the small number of cases in question, an odds ratio of 1.9 would need to be confirmed by testing over other time periods besides the 2002 to 2007 period. The fact that no association was found over the entire 1991 to 2007 time period suggests that the "significant" odds ratio for the 2002 to 2007 time period was due to chance.

Read the entire study (PDF) to answer any further questions you may have.

Al Fin epidemiologists were quite disappointed at the low quality of the media coverage offered so far.



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