Re: Interpreting the negative association of Cohen's data and lung cancer by county

[John Goldsmith <gjohn@bgumail.bgu.ac.il>]

Dear Radsafers:
     I have enjoyed the many comments, many of which are quite resource-
ful and provocative.  However, there is a (possible) very simple 
explanation.  Lung cancer incidence has long been known to be higher in 
urban than rural areas; the assumption that this was a reflection of
general urban pollution was widespread, but it is not true.  The primary
reason is that the urban-rural gradient in lung cancer is greatest where 
pollution gradients are low, and in the few locations in which actual
levels of pollution can be included, there is no significant contribution.
Thus, we know that population density is positively associated with lung
cancer in virtually every place it has been looked for.  Its mechanism
is not known.  For understanding Cohen's gradients, let us first 
recognize that lung cancer goes up with population density. His data
clearly show that radon in negatively associated with population density.
Once one accepts that radon is heavy and its source is in the ground, then
it must follow that people in apartments have on the average lower radon 
exposures than do residents in the single family home.
     I have tried to get the data Bernie says is in an "anonymous" file
to illustrate the paradox and to suggest some approaches to reducing its 
impact, but in vain.  This argument is not directed to any hypothesis of
linearity or dealing with a threshold.  It is directed to acceptance of 
the repeatedly shown positive association  of lung cancer to population
density.  Given the known source and dispersion of radon and its confirmation
by measurements in U.S. counties, the relationship could not be other 
than a negative one, unless the contribution of radon was  much greater
than in miners, which is implausable.
      John Goldsmith, Professor of Epidemiology, Ben Gurion University
of the Negev, Beer Sheva, Israel.  gjohn@BGUMAIL.BGU.AC.IL
 

On Wed, 29 Jan 1997, James S Jr Dukelow wrote:

> 
> On 28 Jan 1997 Darryl Kaurin <kaurin@mail.sep.bnl.gov> wrote:
> 
> > 
> > As for the work of Cohen, I was extremely impressed with his analysis.
> > Since the results are extremely surprising, one must question if an
> > ecological study is appropriate, since the radon doses assigned are average
> > values for the entire county.  Cohen's results are not unique, the UNSCEAR
> > 1994 report lists numerous other radon ecological studies - some show a
> > negative lung cancer rate with dose, some non-significant, and some a
> > significant positive lung cancer rate with dose.  I have not read each of
> > the other ecological studies, but one must question the fundamentals of
> > ecological studies for radon, since the results are so diverse.
> > 
> 
> On 28 Jan 1997 Bernard Cohen <blc+@pitt.edu> replied:
> 
> > ---Ecological studies are not very useful as a method for determining
> > dose-response relationships, but, as pointed out repeatedly in my papers
> > (but widely ignored) it is  a valid method for testing a linear-no
> > threshold theory. All other ecological studies try to do the former and
> > hence are susceptible to "the ecological fallacy", but the ecological
> > fallacy is not applicable to my paper.
> 
> On 29 Jan 1997 Jim Dukelow <js_dukelow@pnl.gov> plans to tediously repeat 
> comments he sent to RADSAFE about a year ago when the same issues were 
> being discussed.  The comments seem to still be relevant.
> 
> To wit: 
> 
> Cohen is justified in complaining, since the general tenor of comments on 
> his paper in RADSAFE was (paraphrasing): "It's only an ecological study, 
> so we don't have to deal with its conclusions."  The problem with that 
> sort of comment is that Cohen dealt with it extensively in the paper, 
> arguing that an ecological study was adequate for statistical hypothesis 
> testing of the LNTH, considered as the null hypothesis.  This places the 
> obligation on people raising the comment again to show why Cohen's 
> arguments are mistaken.  As I understand Cohen's reasoning: 
> 
>         1.  He assumes (but as far as I can find, does not explicitly 
>             state) that the radiation dose delivered to the lung of 
>             persons occupying a house is a linear function of the 
>             measured (usually measured in the basement) radon 
>             concentration in the house, implying an equation of the form: 
> 
>                 Dose2lung = alpha * Radon_conc, 
>                
>                 where alpha is the proportionality coefficient.
> 
>         2.  He assumes as the null hypothesis that
> 
>                 Probability of lung cancer/year = beta * Dose2lung.
> 
>             This is just the LNTH dose response assumption.
> 
>         3.  If the distribution of radon concentrations in a county is:
> 
>                 C1, C2, ..., Cn, where n is the number of houses in the 
>             county, then 
> 
>                 Total person-dose to lung = 
>                      the Sum from 1 to n of (alpha*Ci), and
> 
>                 Number of lung cancers in the county per year = 
>                      the Sum from 1 to n of (beta*alpha*Ci) = 
>                      beta*alpha*(the Sum from 1 to n of Ci) = 
>                      n*beta*alpha*(the Sum from 1 to n of Ci)/n = 
>                      n*beta*alpha*(county average radon concentration).
> 
>         4.  Thus, for the linear no-threshold hypothesis, it doesn't 
>             matter how the radon concentrations are distributed 
>             throughout the county, and it doesn't matter how the person-
>             rem total dose is distributed across the population of the 
>             county, the same number of lung cancers will be predicted by 
>             Cohen's assumption about alpha, plus the LNTH assumption 
>             about the dose-response curve (a straight line in this case).  
>             
>             Note that the LNTH is the only dose-response assumption for 
>             which this assertion is valid.  If you introduce ANY non-
>             linearity into the dose-response curve, then the ecological 
>             study is no longer formally adequate, and the impact of the 
>             non-linearity will have to be assessed in order to decide if 
>             the ecological study tells you anything useful. 
> 
> A few other comments about Cohen's paper:
> 
> 1.  I think his assumption about the linear dependence of Dose2lung on 
>     household radon concentration is at least approximately accurate.
> 
>  <<A short summary of Cohen's Health Physics paper deleted here>>
> 
> 4.  Finally, Cohen's analysis of potential confounding factors asserts 
>     that the negative correlation between county average radon 
>     concentrations and county lung cancers rates is so strong and so 
>     striking that it can stand a lot of confounding by other factors, and 
>     still leave intact the conclusion that the probability that the LNTH 
>     applied to radon dose to the lung is correctly predicting lung cancer 
>     rates is vanishingly small.  Or, to state it baldly, the null 
>     hypothesis (the LNTH applied to radon-derived lung doses) can be 
>     rejected at a high level of significance. 
> 
> 5.  I can't claimed to have verified all of Cohen's statistical 
>     arguments, but I have read through the paper a couple of times in 
>     some detail and find Cohen's treatment of possible confounding 
>     factors and of complaints about the ecological analysis plausible. It 
>     seems to me that anyone who wants to reject Cohen's conclusion has an 
>     obligation to deal explicity with the details of his analysis. 
> 
> I may be missing something here, in which case I would be happy to be 
> corrected by those who better understand these issues.
> 
> Note added on 29 Jan 1997:  No such corrections surfaced when these 
> comments were posted on RADSAFE about a year ago.
> 
> Best regards.
> 
> Jim Dukelow
> Pacific Northwest National Laboratory
> Richland, WA
> 
> js_dukelow@pnl.gov
> 
> These are my opinions and have not been reviewed and/or approved by my 
> management or by the U.S. Department of Energy.
> 
>