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Iowa radon vs lung cancer study - response to Cohen




Radsafers,

With hesitation, I am writing a limited response to Dr. Cohen's recent 
posting concerning the Iowa Radon Lung Cancer Study.  I have been answering 
Dr. Cohen's questions about the Iowa Radon Lung Cancer Study via direct 
email.  I would have preferred to continue the direct email approach to 
scientific dialogue.  Obviously, I do not feel the listserv is a scientific 
forum and scientific correspondences are better left to letters-to-the-editor 
or direct correspondence.  I therefore urge Dr. Cohen to either write a 
letter-to-the-editor of the AJE if he thinks his comments have any scientific 
merit or continue his direct dialogue with me.  At the risk of setting off a 
cascade of emails, I will respond briefly to Dr. Cohen's comments.  These are 
my views and may or may not represent the views of all the authors of the 
Iowa Radon Lung Cancer Study.  Any formal journal responses will represent 
the views of the authors.  That is why I would have preferred addressing 
these issues (along with the other authors) in detail in a scientific arena.  
However, I felt Dr. Cohen's public criticisms on the listserv compelled me to 
respond on the listserv.  In the end, Dr. Cohen and I will likely have to 
agree to disagree on many of these points as we have so many times before.  

It is of note that the Iowa Radon Lung Cancer Study has published numerous 
exposure related method's papers including:

Field RW. Steck DJ. Lynch CF. Brus CP. Neuberger JS. Kross BC. Residential 
radon-222 exposure and lung cancer: exposure assessment methodology. Journal 
of Exposure Analysis & Environmental Epidemiology. 6(2):181-95, 1996 Apr-Jun.

Fisher EL. Field RW. Smith BJ. Lynch CF. Steck DJ. Neuberger JS. Spatial 
variation of residential radon concentrations: the Iowa Radon Lung Cancer 
Study. Health Physics. 75(5):506-13, 1998 Nov.

Field RW. Smith BJ. Brus CP. Lynch CF. Neuberger JS. Steck DJ. Retrospective 
temporal and spatial mobility of adult Iowa women. Risk Analysis. 
18(5):575-84, 1998 Oct.

Steck DJ. Field RW. Lynch CF. Exposure to atmospheric radon. Environmental 
Health Perspectives. 107(2):123-7, 1999 Feb. 

None of these methodologic papers received any criticisms on Radsafe.  Nor, 
were letters written to the editor of the journal, where they were published, 
criticizing the methodology.  The first criticisms of our methodology, by Mr. 
Fumento and Dr. Cohen, arose only after we published our study findings.  
Responses to Mr. Fumento's criticisms and ad hominem attack are detailed 
elsewhere: http://www.cheec.uiowa.edu/misc/radon.html .     Short responses 
to Dr. Cohen's comments follow:  

----------------------------------------
Dr. Cohen states, "The principal reason why the Iowa study is claimed to be 
better than previous studies is that they did a more elaborate job of 
estimating radon exposure doses, by considering exposures outside the home 
and time spent in various places inside and outside the home.  I view these 
improvements as relatively unimportant because of the other much larger 
uncertainties in radon exposures".


Field:  The importance of accounting for mobility is obvious by examining the 
impact on risk estimates if the mobility is not accounted for (see Figure in 
AJE paper).  Health Physicists know the importance of both concentration and 
time in exposure assessment.  If you do not account for where the time is 
spent, you are left with assessing risk based solely on concentration as 
previous residential radon studies have done.  Dr. Cohen may view these 
improvements as relatively unimportant, but he has no data to support such a 
claim.   

The other reason the Iowa Study obtained better exposure estimates is 
completely ignored by Cohen.  Previous residential studies that did not have 
the minimum residency requirement of 20 years had to impute a sizable portion 
of missing data for the previous 20 years prior to lung cancer or prior to 
enrollment.  This decreased the power of previous residential radon studies.  
The importance of the minimum 20-year residency is detailed in the AJE paper. 
 

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Dr. Cohen states, "For one example, they consider only exposures 5-19 years 
prior to cancer diagnosis, neglecting earlier exposures; among the Japanese 
A-bomb survivors, the majority of lung cancer deaths occurred more than 20 
years after exposure, and according to the BEIR-VI models, the same should be 
true of lung cancers induced by radon." 

Field: I would suggest that Dr. Cohen review BEIR IV to look at the temporal 
weighting factors derived from miners.  The Iowa Study was the only 
residential radon study, other than the study performed in Finland, which did 
not have to impute missing radon data for the prior 20 years.  In fact, a 
large proportion of Iowa Subjects lived in the study home for periods 
exceeding 30 years.  See AJE paper for details.

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Dr. Cohen states: "Moreover, the procedures they use to take into 
consideration the time spent in various places introduces a whole new set of 
uncertainties derived from problems in remembering and reporting habits from 
5-19 years earlier."

Field: The retrospective dose assessment methodology was very detailed.  The 
assessment methodology was reviewed by at least two reviewers for the 
American Journal of Epidemiology and several reviewers from the Journal, Risk 
Analysis.  The methodology describing the retrospective mobility assessment 
is available for review in the journal.  The stable time periods in the 
subjects' life were anchored by life events.  For example, women know when 
they were married, when they were working, when they had children, etc.  
These life events were used to frame the time periods.  Please see the paper 
describing this methodology for more details.  Nonetheless, greater 
uncertainty in retrospective mobility is attributable by assuming a constant 
home occupancy such as 75%.

For more details:

Field RW. Smith BJ. Brus CP. Lynch CF. Neuberger JS. Steck DJ. Retrospective 
temporal and spatial mobility of adult Iowa women. Risk Analysis. 
18(5):575-84, 1998 Oct.

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Dr. Cohen states, "Are these memories unbiased by more recent times when the 
cases 
 were sickly while the controls were healthy?" 

Field: The memories are anchored by life events.  There is greater bias by 
assuming cases and controls both spent 75% time in their home.
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Dr. Cohen states: "Does the interviewer treat cases and controls without 
being biased by the fact that the former are sick and dying while the latter 
are healthy?" 

Field: The interviewer was blinded to case/control status.  However, in some 
instances, it was obvious the case was sick.  However, there were also 
controls that appeared ill.  What biases does Dr. Cohen feel may be 
introduced?  Remember, the major questionnaires were mailed to the 
participants and filled out by the participants prior to the on-site visit.
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Dr. Cohen states, "There are also uncertainties in that radon levels in a 
particular house may have changed over time. For example, a crack may have 
developed (or conversely, have become sealed) in the basement floor, causing 
the radon level to be different 15 years ago than it was in the recent 
measurement. Similar problems can arise from
changes in ventilation; do window opening habits and use of air
conditioning remain unchanged over 20 years, let alone between hot and
cool Summers?"

Field:  This is more of a problem for studies that go back and assess the 
radon concentrations in previous homes.  Obviously, the new owners may have 
different behaviors as far as opening windows etc. than did the subject.  
Also, when someone new moves into a home, they are more apt to make 
structural changes than people who have lived in their homes for over 20 
years.  Also, remember - the most important predictive factor for radon in 
the home is source strength - source strength remains stable over time. 

We excluded cases and controls that mitigated their home for radon.  We also 
looked at changes that may have affected radon concentrations over time.  The 
major changes that occurred that may have affected the radon concentrations 
was the switch over in the 1960s and early 70's to central and window air 
conditioning.  The window opening behavior of the subjects was stable over 
the years.  We did note a higher degree of difference in repeated year 
measurements for the homes after the subject had passed away.  The COV for 
repeated second year measurements is reported in the AJE paper.

We also placed glass-based retrospective radon detectors at each study home.  
These will provide additional data to assess the retrospective radon progeny 
exposure.  These findings were not included within the main Iowa Study 
Findings (gas measurement paper) paper.  For more information on the 
methodology see:

Field RW. Steck DJ. Parkhurst MA. Mahaffey JA. Alavanja MC. Intercomparison 
of retrospective radon detectors. Environmental Health Perspectives. 
107(11):905-10, 1999 Nov. 

------------------------------------------------------------
Dr. Cohen States: "For these reasons, I do not accept the claim that this 
study is far superior to the others. Uncertainties in radon exposures are 
important factors in all of them."

Field:  As reasonable people sometimes have to do, we apparently will have to 
agree to disagree on this topic.  

---------------------------------------------------------- 

Dr. Cohen States:  "The aspect of this study that bothers me most is that the
 corrections for time spent in various places makes a very large difference
 in the results, greatly enhancing their conclusion that radon exposure is
 important, in spite of the fact that the average percentage of time spent
 in various places is essentially the same for cases and controls: for
 cases vs controls, average percent of time spent in the home is 73.2 vs
 72.1, in another building is 14.2 vs 14.4, outside is 7.6 vs 8.5, and away
 is 5.0 vs 5.0. While I can understand that mathematically it is possible
 that  correcting for where each individual spends her time can make a big 
 difference from considering onle the averages, it seems very
 difficult to see how the effect can be so systematic as to grossly affect
 the results. It seems to me that the authors owe us some explanation to
 help us understand such a seemingly improbable situation."

Field: As I have pointed out before in my discussions with Dr. Cohen, you can 
not always look at summary data findings and be able to explain the details 
of the individual data linkages between radon concentrations and 
retrospective mobility.   We were limited in some discussions in the AJE 
paper since we had already slightly exceeded our space limit in the AJE 
paper.  We have almost completed a paper that examines the a priori risk 
assessment model used by the Iowa Study versus alternative scenarios that did 
not include consideration of where the time was spent by the subject.  The 
paper in the works contains a more detailed discussion than what is included 
in the AJE paper.
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Dr. Cohen states. "Another problem that bothers me is that there is no 
consideration given to geography, which is a potential confounding factor 
very closely  correlated with radon levels. Controls are chosen randomly from 
the entire  state of Iowa, where average radon levels in different counties 
varies by  a factor of 3, from 1.7 to 5.0 pCi/L. Cases come largely from 
areas where  there is a high prevalence of smoking, which might easily have 
different  average radon levels than the controls. It seems important to me 
that  information be given at least on what counties the cases and controls 
come from."

Field:  Dr. Cohen, I understand your focus on average county radon 
concentrations given your previous research.   However, the range of radon 
concentrations within a county is much greater than the range between 
counties.  We did not use mean county radon concentrations to assess radon 
exposure, we used individual data for each subject.  In fact, in a 
preliminary analysis we have found that mean county radon concentrations are 
a poor predictor of both individual radon exposures and home radon 
concentrations in Iowa.  

Some studies have suggested that radon concentrations may be lower in urban 
areas.  The prevalence of smoking is higher in urban areas.   In fact, Dr. 
Cohen's ecologic data shows an inverse relationship between smoking 
prevalence (based on tobacco sales tax in a county) and radon concentrations. 
  If smoking is indeed related to radon concentrations, it would likely 
minimize finding any association between radon exposure and lung cancer.

 If some factor that caused lung cancer (confounder) was co-correlated with 
geography, it likely would be associated with urban/rural status.  However, 
urban/rural status was not found to be a significant factor in our analyses.  
  
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Dr. Cohen States:  "The cases are nearly all smokers while the controls are 
nearly all  non-smokers. There are many differences in life styles of smokers 
and  non-smokers that can affect radon exposures. Some attention should be
 given to these. Also there is a substantial difference in educational
 attainment between cases and controls which could be a source of trouble.

This is one example of socioeconomic variations which can be important  both 
in disease vulnerability and in radon exposures, but essentially no attention 
is given to socioeconomic factors other than education."

Field:  The inclusion criteria of 20 years in the current home provided a 
match that made the educational status and socioeconomic status between the 
cases and controls much closer than previous residential epidemiologic 
studies.    In addition, the analyses were adjusted for education.  I would 
like to know what data Dr. Cohen is using to demonstrate these other 
unidentified socioeconomic factors were not adjusted for as part of the 
adjustments we made for smoking, education and age.

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 Dr. Cohen States: "The  basis for a case-control study is that cases and 
controls are matched in  every way except for having contracted the disease. 
Any deviation from  this would seem to be an issue for concern."

Field:  This is an erroneous statement.  What Dr. Cohen describes here is 
overmatching.
  
Dr. Cohen says in a case-control study the cases and controls are matched "in 
every way except for having contracted the disease".  Dr. Cohen, I 
respectfully request a reference for this statement.  For example, if your 
statement was true, we should have matched the cases and controls by radon 
concentration, mobility, shoe size, eye color, favorite ice cream flavor, 
etc.   
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Dr. Cohen,

I would be glad to continue the dialogue with you or others to further 
discuss some of these points via direct email to mailto:bill-field@uiowa.edu. 
 As I indicated above, we are still working on several other papers using 
Iowa Radon Lung Cancer Study data including analyses using the glass-based 
retrospective radon progeny detectors.   These papers will provide additional 
information about the study and furether address some of your questions.

Regards, Bill Field 


To Radsafers:

I appreciate the kind words many members of the silent majority of Radsafe 
have conveyed to me directly concerning the Iowa Radon Lung Cancer Study.  It 
is nice to know you are out there.  I know some members of the Radsafe 
community will attack this post.  I understand that they want to put their 
spin on things.  I know of no other epidemiologist that would take the time 
to respond to postings on this listserv (Believe me - I wish there were).  
Sometimes, I wonder why I do.  It must be that I worked as a Health Physicist 
prior to working as an environmental epidemiologist.  I welcome the dialogue 
and have never been one to shy from scientific discussions.  However, if you 
are going to criticize the posting, please read the main paper and referenced 
papers first.  If you have comments about the posting, I humbly request that 
you email me directly.  As you can understand, I really am limited in the 
amount of time I have for public posting since each public post creates a 
cascade of questions via private emails.  


Sincerely, Bill Field




R. William Field, Ph.D.
College of Public Health
Department of Epidemiology
Department of Occupational and Environmental Health
N222 Oakdale Hall
University of Iowa
Iowa City, Iowa  52242

319-335-4413 (phone)
319-335-4748 (fax)
mailto:bill-field@uiowa.edu


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