cancer risks at low doses among a-bomb survivors
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7/28/2019 Cancer Risks at Low Doses Among a-Bomb Survivors
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#Cancer risks at low doses among A-bomb survivors
Return to Table of Contents RERF Update Volume 12, Issue 1, SpringSummer 2001
Cancer Risks at Low Doses among
A-bomb SurvivorsDonald A. Pierce and Dale L. Preston
Department of Statistics
Table. General summary of the 19581994 cancer incidence data
Colon dose, Sv (distance) Subjects Solid cancers Estimated excess
>3,000 m 23,493 3,230 100
0.005 Sv)
part of the populationabout 35,000 persons pre-
senting 5,000 cancer cases so farhad doses in therange 0.0050.02 Sv of primary interest for radia-
tion protection. The real limitation of the study is not
lack of information about low doses, but that the ex-
posures were only acute. As for the secondcharacterization, it is important to realize that results
from conventional analyses are virtually unchanged
if the comparison group of those more than 2 or 3
km from the bombs, about half the study cohort, is
simply omitted from the analysis. This is because of
the large size of, and the wide variation in doses
within, the proximal component.
Moreover, there is some interplay between the two
issues of directly estimating low-dose cancer risks
and whether this distal comparison group is em-
ployed. It appears that the largely rural population
beyond 3 km has had about 5% higher cancer risks
than the part of the urban population with doses of
nearly zero. Such demographic variations in cancer
rates are in general quite common. Such a bias would
have negligible effect on inferences about risks at
high doses; but eliminating it becomes a critical is-sue when estimating cancer risks at around 0.1 Sv,
where the radiation risk may also be on the order of
5% of normal cancer rates. It greatly strains any epi-demiological investigation to estimate risks of this
level, since within the scope of the study cancer rates
may vary to that extent due to other risk factors cor-related with the exposure under investigation. But
the special features of the RERF study, including its
large size, adequate dosimetry, and especially the very
sharp variation of dose with distance (decreasing by
1/3 each 100 m), may make this possible with rea-
sonable confidence. This is extremely rare in any kindof observational study, particularly in epidemiology.
The following table is not intended for analysis,
since adjustment for age and sex is crucial, but ratheris given for perspective on the study.
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$Cancer risks at low doses among A-bomb survivors
Return to Table of Contents RERF Update Volume 12, Issue 1, SpringSummer 2001
This tabulation shows that there are large num-
bers of survivors in the study with low doses, and
also that there remains a large comparison group if
those beyond 3 km are omitted. The estimated ex-
cess was computed from a linear regression on dose,but with an additional parameter for the group be-
yond 3 km.
Our primary analytical description is given by the
following figure for which the underlying methods are
documented in our paper. The aims of this plot are to
display the data as clearly as possible, and to pro-
vide an unconstrainedor nonparametricestimate
of the dose response function. At the same time, we
wish to avoid to the extent possible effects of utilizing
arbitrary dose categories. We achieve that by comput-
ing rather imprecise risk estimates for a large number
of categories and then smoothing the results as shown.The primary focus when looking at such plots should
be the smooth curve, and we emphasize that the dashed
curves are 1 SE limits for the solid smooth curve,
rather than for the plotted points.
We have no idea of the meaning of the bump at
around 0.2 Sv, but note that it occurs in bothHiroshima and Nagasaki.Whether it is statistically
significant is questionable, due to difficulties in test-
ing effects suggested by the data. The main point of
the plot is that there is no indication that low-dose
risks are overestimated by linear regression on the
full dose range. There is statistically significant risk
in the dose range below 0.1 Sv (P = 0.05, one-sidedtest). The upper 95% confidence limit for a thresh-
old, beyond which the risk increases linearly from
zero, is 0.06 Sv. It is visually clear, in view of the
alternative baseline shown, that these inferences
would change substantially if the restriction to
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%Cancer risks at low doses among A-bomb survivors
Return to Table of Contents RERF Update Volume 12, Issue 1, SpringSummer 2001
We indicate in our paper why the physicists involved
in radiation transport calculations find such a dis-
tance relationship for neutron doses physically
impossible, bringing into question the interpretation
of the measurements. These issues are currently un-der study by a bi-national group of physicists. In the
paper we investigate consequences of a more mod-
estbut perhaps still too largemodification that
reduces the factors given above to 1, 5, and 15. We
also employ for this a variable neutron relative bio-
logical effectiveness (RBE), taking values of about
10 at high survivor doses and about 40 at low survi-
vor doses, since the likelihood of such a variable RBE
is a reason that many expect neutron estimate modi-
fications to be potentially important. Our tentative
conclusion is that such a neutron dose estimate modi-
fication would not result in less apparent linearity of
the dose response than seen in the figure here.
So to summarize, our paper clarifies thatcontrary
to widespread viewsthe RERF data provide substan-
tial direct information about low-dose radiation risks
for cancer. Further, the available information is by no
means restricted to that from comparison of A-bomb
survivors to some group not experiencing the disas-ter. For inference about low-dose risks it is necessary
to take particular care in the choice of comparison
population, which is equally true of any low-dose study
of human radiation risks. The very rapid decrease of
radiation dose with distance from the bombs means
that useful comparisons are available between per-
sons within a narrow distance range. Since substantial
heat and blast effects reached further than radiation,
those persons experienced similar effects of thebombings, e.g., severe disruption of their lives, aside
from radiation dose.
Our results indicate that cancer risks for doses on
the order of 0.05 Sv are not overestimated by the
usual regression analysis on much wider dose ranges,
such as 02 Sv. In our analysis there is direct statisti-
cally significant evidence of risk in the dose range of
approximately 00.1 Sv, but we emphasize that this
mode of reasoning, and certainly the precise limits
of such a range, should not dominate interpretation
of the data. In view of the highly linear dose response
down to low doses, it is neither sound statistical in-terpretation nor prudent risk evaluation to take the
view that the risk should be considered as zero in
some low-dose range due to lack of statistical sig-
nificance within that range. To do this would be to
base risk protection on the smallest plausible risk at
those low doses, since in statistical reasoning a non-
significant result means precisely that the lowerconfidence limit is zero or less. There is every rea-
son to conclude from the RERF data that the usual
linear cancer risk estimation is appropriate for low
doses.
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