Re: New Multiple Myeloma Study

["Jerry Cohen" <jjcohen@prodigy.net>]

Ron,
    What is  "an appropriate level of safety."?

JJcohen@ prodigy.net

-----Original Message-----
From: Ron L. Kathren <rkathren@tricity.wsu.edu>
To: Multiple recipients of list <radsafe@romulus.ehs.uiuc.edu>
Date: Monday, April 10, 2000 10:58 PM
Subject: New Multiple Myeloma Study


>While I make no brief for or against the "new" multiple myeloma study by
>Wing et al., since I have not read it, it might be instructive to look at
>the already published literature with respect to radiation and multiple
>myeloma.   Gilbert was not the only one who saw an apparent association
>between multiple myeloma and low level irradiation.  BEIR V (pp. 327 ff.),
>citing Cuzik, notes that such an increase in multiple myeloma was observed
>in 12 of 17 irradiated populations, with an overall O/E of 2.25 (50 cases
>observed to 22.2 expected).  NCRP Report 121, published 5 years after BEIR
>V, tabulates no less than 42 studies (Table 3.4, pp. 35-36) with various
>populations and exposures (including those cited by Cuzik, except where
>later analyses were available for the same populations) coming up with an
>observed:expected ratio of 1.17 for the combined studies (503 cases
>observed; 431 expected).  Somewhat more than half of the studies showed an
>O/E ratio > 1, with by far the largest ratios (5.2, 5.7, 6.2) occurring in
>the three studies of Thorotrast patients.  If these three relatively small
>Thorotrast studies are excluded, the O/E ratio changes only slightly, to
>1.14, 491:429.   Interestingly, the 42 studies tabulated in NCRP 121 did
not
>include the 1979 paper by Gilbert cited by Otto Raabe but instead included
a
>later (1993) publication regarding the Hanford cohort which showed no
excess
>of multiple myeloma (O/E = 0.9, 25 cases observed vs. 27.4 expected) but
did
>show a marginally positive slope dose -response.
>
>While the Wing et al. study may (and likely does) have its problems, I
think
>there are enough data from earlier studies to reasonably conclude (or at
>least strongly suggest) that there is likely an association between low
dose
>irradiation and multiple myeloma.  Whether this is age dependent remains to
>be seen.  But in any case, my first impression is that the Wing et al.
study
>does not appear to be too far afield from what has been observed in a
number
>of other studies.  According to the local newspaper reporter who just
>called, Wing et al. have apparently indicated that based on their study the
>exposure limits should be reduced.   Whether or not the recommended
exposure
>limits should be lowered on the basis of the study by Wing et al. is at
this
>point an interesting speculation, but it is just that -- speculation that
>begs additional study to verify that the existing limits provide an
>appropriate level of safety.
>
>Ron Kathren
>
>
>
>
>
>
>----- Original Message -----
>From: Otto G. Raabe <ograabe@ucdavis.edu>
>To: Multiple recipients of list <radsafe@romulus.ehs.uiuc.edu>
>Sent: Monday, April 10, 2000 3:33 PM
>Subject: Re: New Multiple Myeloma Study
>
>
>> April 10, 2000
>> Davis, CA
>>
>> Steve Wing's UNC study of 4 labs was discussed in RadSafe in detail in
>> 1998. Here is a copy of one of the messages I sent in February, 1998:
>> *****************************************
>>
>> February 3, 1998
>> Davis, CA
>>
>> Dear All:
>>
>> Yesterday Steve Epperson posted the abstract of a new study by Steve Wing
>> about risks to radiation workers. Dr. Wing is an epidemiologist at North
>> Carolina who personally believes that the nuclear industry is evil.
>>
>> In the 1970's it was noted by Gilbert et al. (Rad. Res. 79:122-128, 1979)
>> that there was an apparent association of some extra cases of multiple
>> myeloma among radiation workers at Hanford. This was considered a random
>> observation, since it was not found in other studies. Also, remember that
>> if you look at every possible type of cancer, ignore those that are lower
>> in exposed groups, and look only for those that are elevated, it is
>> possible that you will find at least one type of cancer that seems to be
>> associated with radiation exposure. That observation is expected by pure
>> chance. Then if you ignore everything else, you could claim that this
>> random observation proves that radiation is responsible even at the low
>> levels of exposure received by radiation workers. This the the method
used
>> by some epidemilogists who really want something to report.
>>
>> Okay. What Wing did was get money from NIOSH to study myeloma cases at
>> Hanford but incorporating data from other laboratories including LANL,
>ORNL
>> and SRS. In his abstract he notes that there also were confounding
>> exposures of the radiation workers to many other agents "including
>> solvents, metals, welding fumes, asbestos,....and non-ionizing
radiation."
>> However, only exposures to ionizing radiation were quantified well enough
>> for him to include in his analysis!
>>
>> This was a case control study where all the cases of myeloma deaths were
>> matched with control persons who lived to the same age, but did not
>develop
>> myeloma. When radiation exposure was considered he found: "Total
>cumulative
>> radiation doses were similar between cases and controls." NO RADIATION
>> EFFECT! Well, that wasn't the right answer, so now he started subdividing
>> the data and found that if he only considered people whose exposures
>> occurred at ages 45 or older, there was a significant association of risk
>> of myeloma with radiation exposure after age 45 "adjusted for age, race,
>> sex, facility, period of hire, birth cohort, monitoring for internal
>> radionuclide contamination, and external radiation received prior to age
>> 45." This observation is the whole basis of his report. He reports an
>> increased incidence of a factor of 4.3 for workers receiving doses
greater
>> than 5 rem. [Review of the A-bomb survivor data shows a dose of above 100
>> rem delivered instantaneously was required to yield this large an
increase
>> in multiple myeloma cases and simultaneously yielded about a seven-fold
>> increase in leukemia cases (BEIR V).]
>>
>> Wing claims that increased cancer sensitivity in older workers is
expected
>> theoretically and found in some other studies. Actually, my reading of
>BEIR
>> V shows a consistent reduction in risk of radiation induced cancer of all
>> types with increased age at exposure! Also, if this is a radiation effect
>> rather than a chance observation, we would expect that other cancer types
>> would be more readily observed, such as leukemia and lung cancer, but
>> apparently not.
>>
>> Wing's results show no overall effect until selectively grouped to
achieve
>> an observed level of significance. You can guess that he tried every
>> conceivable combination of age grouping to harvest a significant
>> observation from the study so that he could declare that his "findings
and
>> other studies of nuclear workers have implications for radiation
>protection
>> standards for workers and the general public."
>>
>> Finally, the observations by Wing that there is no overall effect, but
one
>> remarkably appears when considering exposures of people older than 45,
>> suggests that there must be a protective effect for exposures that occur
>at
>> ages younger than 45. This is because overall he found that: "Total
>> cumulative radiation doses were similar between cases and controls." NO
>NET
>> EFFECT!
>>
>> Otto
>>
>> *****************************************************
>> Prof. Otto G. Raabe, Ph.D., CHP
>>               Institute of Toxicology & Environmental Health (ITEH)
>>    (Street address: Building 3792, Old Davis Road)
>> University of California, Davis, CA 95616
>> Phone: 530-752-7754  FAX: 530-758-6140
>> E-mail ograabe@ucdavis.edu
>>               *****************************************************
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>
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