This is a the third and final review of a paper that was presented to me by Mr. Newman. To recap – In a previous post, in the context of residential radon and lung cancer risk, I had laid down a challenge:
If any Home Inspector can find one, ONE – just ONE scientifically valid study that conclusively demonstrates, with no confounders, that radon concentrations as normally found in homes significantly increases the risk of cancer, I will profusely apologize, reconsider my thoughts and buy them dinner at the Brown Palace Hotel in Denver.
In response, one forum participant merely kept regurgitating the same studies over and again (not realizing that they represented a single study over and again) and ignoring the fact that the referenced studies had already been addressed. One participant, however, (Mr. Newman), provided three such studies that he claimed satisfied the challenge and supported his contention that exposure to residential radon posed a serious threat to residential health, and the articles supported his position.
In the case of the first article, the study had nothing to do with residential radon whatever, but rather studied cancer rates among slave laborers in forced labor camps working in unventilated underground uranium mines. The second article was a amateurish attempt to take 13 European studies that showed no elevated risk of cancer due to residential radon, and then make up new exposures values that would result in some risk. It was evident that Mr. Newman didn’t actually read the studies before offering them as support.
The third article, which I will review here, is a very interesting and a very good article. It is curious that this study was the last of the three since the previous two reviews actually lay a foundation for this review. Funny how things work out.
I have reviewed the article titled: *Residential Radon and Risk of Lung Cancer in Eastern Germany * (Kreuzer, M; Heinrich, H; Wölke, G; et al, Epi 2003; 14; 559-568).
Overall, the study appears to be very well constructed, very well thought out, and meticulously conducted. The authors appear to have very carefully planned the study giving tremendous amount of effort to understanding and, hopefully, address potential confounders and biases.
Ultimately, the credibility of an epidemiological study assessing cause and effect, lies in four elements: 1) Properly estimating dose, 2) Properly identifying biological end points, 3) Properly addressing confounders, and 4) Properly addressing bias.
In this case, the authors appear to have worked very hard to ensure that each of these elements have been met, to within any reasonable expectation. The study, appears to have been conducted in accordance with good experimental methodologies, and good scientific principles, and the final work product has exhibited, in my opinion, a very high degree of epidemiological aptitude, and as a result, the study displays very high credibility, and is a valuable reference.
The study, however, does not support Mr. Newman’s belief system, and does not meet the challenge and my award dinner is safe. I suspect, that once again, just as in previous cases with these two posters, Mr. Newman never actually read the study, but rather assumed, based on the title only, that the study must support his position since it sounded rather official. I have given Mr. Newman the benefit of the doubt in these three studies. In the future, I recommend that Mr. Newman actually read an article before he references it. I will demonstrate why I know Mr. Newman never read past the title of this study in a moment.
The authors of the study set out to characterize risk vs. residential radon exposure. Their tacit hypothesis was: There is no correlation between lung cancer and radon exposure among individuals who are exposed to elevated residential radon. The authors tested the hypothesis and failed to find supporting evidence for the hypothesis and (appropriately) accepted the null hypothesis.
To test their hypothesis, the authors selected an area in Eastern Germany whose radon concentration is so high, that the normal OUTDOOR concentrations to which people are exposed, is HIGHER than most indoor readings in the US.
The authors selected this area because it did NOT represent normal residential radon concentrations since they realized that if an association actually did exist between residential radon and lung cancer, the association was so weak, that it probably could not be observed in normal residences.
Indeed, the authors recognized the association was in fact so weak, that special attention needed to be given in this study to smoking, or the risks may not be observable (if they exist at all).
The type of study is known as a “case-control” study wherein the life styles of predetermined lung cancer patients (cases) are compared to “randomly” selected people in an area (the controls). The case-control method automatically introduces a type of an error called “systematic error” which may “bias” the results one way or the other, since in fact, the controls are not random, and the cases may not actually have cancer as a result of radon exposure. The authors, however, adequately explain how they worked to correct for such biases, however, they admit that at this point in time, we simply cannot adequately control for bias in all studies.
The first sentence of the study’s prologue sets the stage for the presentation and demonstrates that Mr. Newman never read this article. The authors begin with:
There is suggestive evidence that residential radon increases lung cancer risk.
To those of use who work in the field of epidemiology, the term “suggestive evidence” is a standard concept which speaks to “association,” but not to “cause.” In my second review, (found here: http://www.nachi.org/forum/showthread.php?t=12695 ) I gave an example of this concept where a fictitious researcher (Dr. Greene) concluded (very correctly) that “There is suggestive evidence that storks increases babies.” Dr. Green did not conclude that storks cause babies, but rather that there was a strong and consistent association between storks and babies; this is suggestive evidence.
Another reason why I believe that Mr. Newman did not read this study is because he has stood by the unsupported idea that the risk from miners can be extrapolated to residential settings, yet the THIRD sentence in the paper that he claims to uphold his ideas makes the following statement:
A direct transfer of risk estimates derived from studies of miner to residential environments is not possible due to substantial differences in the levels of radon exposure, confounding factors … differences in age and sex of affected subgroups, and differences in other physical factors such as breathing rate, the size distribution of aerosol particles, the unattached fraction of radon progeny and others.
This statement is consistent with good science, known facts, and my opinion for almost 20 years. This statement is NOT consistent with posters on this board, who ignore the vast overwhelming number of studies that hold this position, but who claim that miner’s studies prove that residential exposures to radon causes cancer (for which not a single valid study on the Planet Earth exists).
So, for the benefit of Mr. Gromicko, it’s worth repeating:
A direct transfer of risk estimates derived from studies of miner to residential environments is not possible…
(I just don’t know how many times, by how many different people he needs to hear this from.)
The authors of the present study, then lay the groundwork for what IS known:
In the past decade a series of well-conducted epidemiological studies has investigated the risk of lung cancer in relation to indoor radon exposure directly via case-control studies. Some of these studies have found a statistically significant increased lung cancer risk, and other studies have not.
The idea that all scientists conclude that there is concrete evidence to support the notion that exposure to residential radon significantly increases the risk of lung cancer is simply not borne out. Indeed, all of the knowledgeable scientist whom I know and work with have opinions that are similar to mine – they HAVE to be, because that is what the scientific data show.
The authors of this article note that for ALL of these studies, uncertainty in assessment of exposure, low statistical power and a limited range of radon concentrations impede these studies. In one study, referenced by these authors, since it speaks to roughly the same geographic areas, which had good statistical power the authors tell us:
From 1990 to 1996, a case-control study of lung cancer and indoor radon (comprising 1,449 cases and 2,297 controls) was conducted in Western Germany. There was no association between lung cancer and radon exposure across the entire study area.
I’m not going to go into individual confounders or bias except to say the authors went to extreme lengths to understand potential confounders and bias and honestly address them. In my opinion, they did an exceptionally fine job. However, I do need to address two epidemiological points that the authors either appeared to overlook, or they implicitly addressed the issues by reference and I missed it.
The first issue deals with an epidemiological concept known as “clusters.” I’m not going to go into “clusters” in any great detail, otherwise this review would extended onto many, many pages just on that issue. Except to say, the cases appeared to resemble a “cluster.” A recognized difficulty in the investigation of a cluster is that there usually are no predetermined boundaries (spatial or temporal). Rather, (and possibly in this study), the illnesses has defined the boundaries of the cluster.
That is, “the tail has wagged the dog” instead of the other way around. It is possible that in this otherwise exceptionally well conducted study, the cluster may (or may not) have been erroneously defined by the authors. It is generally considered impossible, except in unusual situations, to determine whether the number of cases is in excess of the number that might be attributable to chance without *a priori *defined boundaries. Those *a priori *defined boundaries did not exist in this study.
A second, related, issue involves an epidemiological concept known as “necessary cause vs. contributing factor.” If a disease appears to have a particular single etiology, it may be because we have defined that disease in terms of that cause, and we now end up with what is known as “necessary cause,” instead of a more appropriate classification of “sufficient cause” or “contributing factor.” Here, like a cluster, I wonder if the authors have not crossed this line – since the selectional bias observed by the authors themselves suggest this weakness, but they have not explicitly addressed it. I simply don’t know.
In a nut shell, the authors, consistent with other studies, and consistent with what I have already discussed here, found that the risk of lung cancer behaved in a non-linear fashion and the risk went DOWN as the radon concentration went UP, and then, above a certain point, reversed and the risk began to increase with increasing concentrations of radon.
Also, the authors, undaunted by negative correlations, in my opinion, appropriately handled the negative confounder observed with smoking.
Bottom line: The authors appropriately expressed concerns about their data, and methods, and in the differential diagnosis, found that in this area where even outdoor concentrations are higher than most indoor US concentrations, and indoor concentrations are much, much, greater than in the US:
Our findings suggest a moderate increase in lung cancer risk, which is most pronounced among small cell lung cancer.
The authors place their findings in contrast with other notable studies thusly:
We found a moderate increase in lung cancer risk as a result of residential radon, which is in agreement with the results of previous studies that included direct, long-term measurement of radon using alpha-track detectors. [Three of these] studies reported a statistically significant ERR for an increase of 100 Bq/m3; [six of these studies] observed an elevated ERR that did not achieve statistical significance; whereas no clear effect was found in the remaining [five] studies.
In other words, statistically significant elevated risks were observed in only 3 out of 14 similar good epidemiological studies (three studies showed a risk, and 11 studies failed to show a significant risk).
The findings of these authors are consistent with what I have been saying for almost 20 years now, and are consistent with the opinions and discussions I have presented on this board.
The findings are not consistent with the fear-mongering hype of some participants who try to frighten with nonsensical newspaper reports that quote 4H leaders as the authoritative figure, and who repeatedly reference studies they have never read, and probably won’t ever read, since those very studies they reference oppose their positions.
My dinner bet is safe and my challenge still stands. In the future, I would recommend that before someone references a study and claims that it supports their opinion, they should probably at least read the study first to see what it says.
But then, that’s just me and my old fashioned way – heck, I think snow is cold, so what would I know, eh?
Cheers all! It’s been fun. Feel free to throw stones!
Caoimhín P. Connell
Forensic Industrial Hygienist
(The opinions expressed here are exclusively my personal opinions and do not necessarily reflect my professional opinion, opinion of my employer, agency, peers, or professional affiliates. The above post is for information only and does not reflect professional advice and is not intended to supercede the professional advice of others.)