AW: [ RadSafe ] AW: Low level radiation and cancer:

[Rainer.Facius at dlr.de]

Christian:

Your comments by and large hit instead of being off the marks.

Yet, in some cases it appears you make things more complicated than necessary. E.g., in order to determine the shape of the dose response function I need not subtract a background. I just model the incidence/mortality data with some of the model functions which either have some theoretical justification or which at least are suggested by the data. The 'background' then is just the y-value for zero dose. When you do need a background or reference value as e.g. with standard mortality or incidence ratios, the control population usually is sufficiently large (often it is the whole population) that the related uncertainty is negligible and hence no error propagation is needed. 

I agree that it stands to reason that at low (actually up to quite high) fluxes the amount of damaged molecules initially generated by absorption of radiant energy is proportional to dose. 

What flies into the face of everything we know by now about the biological processing of the initially damaged molecules, is to maintain that the kinetics of these processes are independent from dose or dose rate. 

Hence the whole concept of LNT, once upon a time arguably a legitimate postulate, is simply an outdated obstacle to scientific progress. Instead of testing LNT against all too often inadequate epidemiological data, it suffices to point to by now well established laboratory findings on the molecular, cellular and even animal level which are incompatible with this postulate. So in my view trying to disprove LNT constitutes a futile effort.

Yet, if you so wish, an ecological study of the kind you perhaps envisage has actually been made. The findings by Bernard Cohen on the lung cancer mortality in essentially the whole U.S. population as a function of Radon exposure probably meet your criteria (Cohen B L, Test of the linear-no threshold theory of radiation carcinogenesis for inhaled radon decay products. Health Physics 68#2(1995)157-174) and as to be expected by now, they provide a fulminating refutation of the LNT postulate. 

Further improvement of the assessment of radiobiological health effects (not necessarily detrimental) will depend on a judicious interplay of theoretical insights corroborated by laboratory - including essential animal - studies and epidemiological work designed and analysed with due allowance of these insights. In my view LNT has no more relevance for this progress.

Kind regards, Rainer 


Dr. Rainer Facius
German Aerospace Center
Institute of Aerospace Medicine
Linder Hoehe
51147 Koeln
GERMANY
Voice: +49 2203 601 3147 or 3150
FAX:   +49 2203 61970

-----Ursprüngliche Nachricht-----
Von: Christian Hofmeyr [mailto:chris.hofmeyr at webmail.co.za] 
Gesendet: Sonntag, 7. August 2005 21:24
An: Facius, Rainer
Cc: radsafe at radlab.nl
Betreff: Re: [ RadSafe ] AW: Low level radiation and cancer:

Rainer Facius and others,
I would have liked to follow the discussion of LNT in more detail, but unfortunately I have been suffering from a bad internet connection and furthermore I do not have ready access to a technical library to look up references.  So please bear with me if my offerings seem slightly off the mark.
I believe that solving the LNT conundrum is very important.
 A vindication would be useful in terms of making rational decisions regarding risk.  The first prize would be an indication of a threshold or even hormetic benefit, as it would allay public fears about numerous beneficial nuclear and radiation applications.  It seems to be a tough nut to crack, but some of the problems may be of our own making. 
The first point I would like to raise concerns the statistics of background subtraction. I maintain that one should try and avoid this procedure if at all possible and only use it as an absolute last resort. This is very much at variance with general practice, which scientists seem to imbibe with mother's milk, but the reason is at least
threefold:
1.	Variances add, whether one adds or subtracts variables,
causing a much greater relative uncertainty in the subtracted result.  So much the worse when one is dealing with large uncertainties.  Extracting radiogenic cancers from the total incidence seems a case in point.
2.	One should also not be fooled by 'accurate' knowledge of
the average background - the sampling of the foreground determines the variance on the background relevant to the sample also, irrespective of how well the average background is known.
3.	In many cases one is dealing with Poisson distributions
in which the variance is equal to the average and the standard deviation is therefore its square root.  Now the
clincher:  if one adds two Poisson distributed variables, the result is Poisson distributed, but if one subtracts, the resultant distribution loses its important Poisson quality. 

Now the definition of radiogenic cancer as an excess already implies that one can and should subtract the 'other' cancers (of the same type).  From a general perspective this need not be correct.  By using the concept of excess cancer, one is already forcing a specific additive model of radiogenesis.  A more general approach would also allow e.g. a multiplicative model or a combination.

To get back to LNT:   It stands to reason that the damage
caused by radiation is proportional to the dose, at least in the low to medium dose (and doserate) range.  It is the reaction of biological systems to the rate and amount that might be non-linear.  LNT predicts an outcome which is linear with dose, i.e. either there is no biological response to radiation damage in the organism which counters the outcome, or, otherwise, the effectiveness of the response is constant with dose (i.e. proportional to dose from zero up).  This implies that every bit of dose counts and the number of resultant radiogenic cancers is directly proportional to the collective dose of any suitably defined group.  This forecast is the most risky one for LNT and IMO provides the most sensitive test.  (For this purpose a carefully conceived ecological study could have clear advantages over an epidemiological one.)

In view of my first thoughts,  the logical thing to validate LNT would therefore be to plot total cancer incidence (by type) against collective dose, obviously controlling for a number of variables like age, gender, group size, etc. The basic proviso is that the average dose to the individual must vary. [If group size would not be constrained, one could perform a gedanken experiment which proves LNT: consider a homogeneous or otherwise well-controlled group and vary the collective dose by the size of the group considered! QED.]  If one does not obtain a linear relationship with positive gradient and a positive y intercept, then LNT fails.  This should be infinitely more sensitive than trying to follow excess cancers as a function of individual doses.  It is not necessary or productive to try and subtract a non-radiogenic background (although this compromises the log-log presentation, I guess).  Natural radiation background must be included in the collective dose calculations.  
One can think of interesting possibilities in constituting different cohorts.  Comparison of cohorts living under different ecological radiation conditions could be a very useful approach.  Call me naïve, but I therefore am not completely pessimistic about validating or otherwise disproving LNT within certain confidence limits, as with all physical theories.  The use of collective dose would probably only yield a YES or NO for LNT.  More sophisticated studies would be required to delve into mechanisms if the LNT answer is NO.

The very weakness of radiation as a carcinogen makes it very difficult to control observations adequately for sensitive confounding variables.  Apart from the statistics, important problems are 1. recognition and adequate control of confounding variables, 2. reliability of cancer incidence and mortality statistics, 3. dose and collective dose evaluation and its consistency, 4. choice of time frames, 5. etc.
  
The above proposal is over-simplified.  I have not even touched on the choice of dose definition.  There are complications with e.g. the study of cancer, primarily the very sharp increase of incidence with age, so that controlling for age must be ultra-diligent.  Cohorts could be varied by e.g. excluding and including certain age groups.  It can be assumed that the reliability of cancer incidence and mortality statistics is rather variable between regions and countries. Reliable statistics is a clear prerequisite for a valid LNT study and this reliability would have to be quantified for all relevant variables and the sensitivities established.

Another problem is the effect of confounding changes in lifestyle with time. Particularly lung cancer is very problematic in this regard. The SEER statistics for the USA show a very large gender differential in mortality of almost a factor 5 during the 1970s, which narrowed dramatically subsequently due to a levelling out and slight decline of male lung cancer mortality, coupled with a simultaneous steep rise in female LC mortality since the 1970s.  These dramatic changes are most probably due to changing smoking behaviour.  This should give an indication of the problems confronting domestic radon studies.
Chris.Hofmeyr at webmail.co.za


_________________________________________________________________
Need software for your hardware? Click here http://www.asg.co.za