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OCR for page 111
7
Comparison with Other Studies
CONCORDANCE WITH THE UTAH STUDY OF THYROID DISEASE
FROM NEVADA TEST SITE FALLOUT
Section TX of the Draft Final Report describes in some
detail whether the HTDS study confirms the results of the Utah
study of exposure to i3~l from the NTS (Kerber and others, 1993~.
With a generally negative dose-response relationship, especially
for thyroid carcinoma, the HTDS cannot be regarded as confirming
the Utah findings of increased risk of thyroid neoplasia. However,
another aspect of the comparison of the two studies is not fully
treated: the degree to which the results of the HTDS directly
contradict those of the Utah study. One approach to answering that
question is to assess the degree to which confidence intervals of
risk estimates from the two studies overlap. Even if one study's
results are positive and another is negative, it does not mean that
they necessarily are irreconcilable. If the positive study is barely
positive (p ~ 0.05) and the negative study has wide confidence
intervals, there might be no fundamental disagreement.
For the HTDS analysis of thyroid carcinoma, the
estimate and the confidence interval for the linear slope term for
thyroid carcinoma are not reported, because the maximum-
likelihood estimates failed to converge. We can, however, work
backward from other information in the report to estimate the
standard error of the slope term. The attained power to detect a
OCR for page 112
I12
Review of the HTDS Draft Final Report
slope term of 2.5% per Gy is states} to be 0.96 (section VITT), so we
will have (at least approximately)
0.025/(standard error of B) = (A 0.05 - ZI-0.96) = 3 396
Therefore, the standard error of slope term B must have
been 0.007 per Gy. To approximate the value of the estimate of B.
we note that a logistic mode! did converge and gave an estimated
slope that was about ~ standard error below zero. We can assume
roughly that the linear slope estimate would also have been about ~
standard error less than zero, or about -0.007 per Gy. If (as
hypothesized) males had a background risk of 0.004, the upper
confidence limit for the risk at ~ Gy is -0.007 + 2~0.007) = 0.007,
so the upper limit of the excess relative risk (ERR) at ~ Gy is 1.75
for males. For females, assuming a background of 0.007, the ERR
at ~ Gy is I, so the average of the two is ERR = ~ .375 per Gy. For
the Utah study, the estimate was 7.7 with a lower 95% confidence
limit of 0.74 per Gy. It seems, then, that the confidence intervals
for the risk of thyroid cancer overlap to some degree. Moreover, on
the basis of the considerations above, it is evident that the
confidence intervals for the HTDS in fact depend on dosimetry-
error assumptions; if the pure Berkson mode} of errors in the
dosimetry does not hold, the confidence intervals for the HTDS
could be considerably wider. Thus, there does not appear to be a
fundamental incompatibility between the two studies.
CONCORDANCE WITH STUDIES OF EXTERNAL RAI)IATION TO THE
THYROID
It may be an oversimplification to say that the HTDS,
because it found no significant dose-response relationship for any
disease end point, is in direct contradiction with the cohort studies
of external radiation exposure and risk of thyroid cancer. Of the
five cohort studies of external radiation and thyroid cancer that
were analyzed by Ron and others (1995), one yielded estimated
dose-response relationships considerably stronger than the others.
OCR for page 113
Comparison with Other Studies
~3
To combine the results of the five cohort studies, Ron and others
used a random-effects model. The dose-response relationship was
allowed to vary from study to study, and the average dose-response
relationship for a hypothetical population of studies was estimated.
The average estimate was equivalent to an ERR of 7.7 times the
age-specific baseline per Gy with a confidence interval of 2. I-28.7
times the baseline. As described above, the HTDS is probably
consistent with an upper ERR of about T.4 per Gy, which is not
statistically compatible with the estimate for external radiation. It
is not known whether the two estimates could be statistically
compatible if uncertainties in dosimetry were factored into the
confidence interval for the HTDS.
COMPARISON WITH CHERNOBYL STUDIES
The effectiveness of 13~} in causing thyroid cancer has been
shown by the Chernobyl experience. The first increases, reported
in ~ 992, of thyroid cancer attributed to the accident were
challenged as possibly the result of intensive screening. More
recently (Astakhova and others, 1998), however, a case-control
study in Belarus has found highly significant differences between
cases and controls in estimated ]3~} dose to the thyroid, even when
controls with similar presenting complaints or screening
circumstances were selected. But the durations of exposures were
shorter for Chernobyl than for the Hanford downwinders, and the
doses were higher, so the dose-rate issue still is unresolved with
respect to the epidemiologic data. Furthermore, the dose
reconstruction for the study in Belarus was based on actual
measurements of ground deposition of ]3~{ and cesium-137, a data
bank of 1986 thyroid-radiation measurements, and interviews and
questionnaires. Therefore, doses were probably better estimated for
individuals in the Belarus study than in the HTDS.
Representative terms from entire chapter:
thyroid cancer
