cancer risks at low doses among a-bomb survivors

7/28/2019 Cancer Risks at Low Doses Among a-Bomb Survivors

1/3

#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.


2/3

$Cancer risks at low doses among A-bomb survivors


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


3/3

%Cancer risks at low doses among A-bomb survivors


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.

cancer risks at low doses among a-bomb survivors

Documents