Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 371
LOW DOSE EPIDEMIOLOGIC STUDIES
7
Low Dose Epidemiologic Studies
INTRODUCTION
371
As pointed out in Chapter 1, studies of the imputed effects of irra-
diation at low doses and low dose rates fulfill an important function even
though they do not provide sufficient information for calculating numer-
ical estimates of radiation risks. They are the only means available now
for determining that risk estimates based on data accumulated at higher
doses and higher dose rates do not underestimate the effects of low-level
radiation on human health. As also discussed in Chapter 1, there is good
reason to postulate, on the basis of animal studies, that the carcinogenic
effectiveness of low-LET radiations is reduced at low dose rates, although
the available human data do not suffice to confirm this hypothesis.
In its review of low dose studies reported since the BEIR III report
(NRC80), this Committee considered populations exposed to radiation from
a number of different sources: diagnostic radiography, fallout from nuclear
weapons testing, nuclear installations, radiation in the work place, and high
levels of natural background radiation. Studies of prenatal exposures to
diagnostic x rays are discussed in Chapter 6.
DIAGNOSTIC RADIOGRAPHY: ADULT-ONSET MYELOID LEUKEMLt
A case-control study of patients with chronic myelogenous leukemia
(CML) (Pr88) found that during the 3-20 years prior to their diagnosis, more
cases than controls had x-ray examinations of the back, gastrointestinal (GI)
tract, and kidneys; and cases more often had GI tract and radiographs of
371
OCR for page 372
372 EFFECTS OF EXPOSURE TO LOW AILS OF IONIZING MOTION
the back taken on multiple occasions. A total of 5 cases and 0 controls had
GI tract series done on four or more separate occasions, and 11 cases and
1 control had back x rays done on five or more occasions. The odds ratio
for exposure to 0-0.99, 1.00-9.99, 10.00-19.99, and > 20.0 Gray in the 3-20
years prior to diagnosis were 1.0, 1.4, 1.7, and 2.4, respectively (o for the
highest exposure category, p < 0.05~. The association was strongest for the
period 6-10 years prior to diagnosis, and the effect of radiation exposure
during this period remained significant after consideration of other risk
factors in a logistic regression analysis. It was estimated that 23% of cases
were attributable to exposure to diagnostic x rays during the period 3-20
years prior to the date of diagnosis of the case (17% during the 6-10 years
prior to diagnosis).
These recent findings support the association of adult-onset myeloge-
nous leukemia (ML) with certain types of radiographic examinations and
with multiple such examinations. The findings are similar to those of the
case-control study in New Zealand which found that risk of ML increased
with the frequency of x-ray examination of the back and GI tract (Guam.
In the earlier British and tri-state leukemia studies, it was also noted that
patients with ML were more likely than controls to have had multiple
radiographic examinations (St62, Gimpy.
A study that was without positive risk findings involved a smaller
number of patients (63 patients with ML, including some children) and
used nonleukemia patients as controls. The controls were matched to the
cases by having visited the same clinic at two distinct times (the year when
the patient was diagnosed with ML and the year when the patient first
visited the clinic before diagnosis of ML) (Limb. This algorithm for control
selection may have introduced a serious bias, since controls selected from
among repeat clinical patients are likely to have received more medical
attention (including more x-ray examinations) than the general population.
Summary
The issue as to how much adult-onset ML is attributable to diagnostic
radiography is still unresolved. Questions that have been raised include: (1)
whether the excess radiography may have been for preleukemic conditions;
(2) whether the association between ML and radiography was due to con-
founding by the conditions for which x rays were taken; (3) whether there
were possible sources of bias (selection, recall, etch; (4) host susceptibility
variables; and 5) dosimetry. Leo studies that have attempted to evaluate
questions 1 and 2 have found little to suggest that much of the observed
association was attributable to these sorts of confounding (St62, Pram;
only in the period immediately preceding diagnosis did patients with ML
have more x rays because of infections or vague illnesses, and the strongest
OCR for page 373
LOW DOSE EPIDEMIOLOGIC STUDIES
373
association of ML with radiography was seen not during this period but
during the previous period. The positive studies found that the reasons for
trunk x rays were distributed similarly in cases and controls, but that for
any given reason prompting relatively high bone marrow doses, cases had
more repeat exams.
Potential bias is always a concern in case-control studies. Another
concern and a major limitation of all case-control studies of ML associated
with diagnostic radiography is that the dosimetry is uncertain. Doses for
a typical examination are, therefore, usually assigned if dose estimates
are made at all. A recent dosimetry survey of diagnostic radiographic
procedures performed in the United Kingdom shows that the range of
doses administered for each type of examination is wide (Sham.
FALLOUT FROM NUCLEAR WEAPONS TESTING
In the late 1970s, several studies reported excess cancer, primar-
ily leukemia, among persons who were exposed to fallout from nuclear
weapons tests. These included residents of Utah and neighboring states
downwind of the Nevada Test Site (NTS) and veterans who had participated
in the tests. Estimates of the doses to most organs in both groups was re-
ported to be sufficiently low (less than 50 milliGray for all tests combined)
so that no detectable increase in risk would have been predicted on the
basis of cancer risk estimates derived from high-dose studies. A possible
exception was the dose to the thyroid, which exceeded 500 mGy in some
individuals (studies of thyroid tumors are reviewed in Chapter 5~.
Cancer Among Residents Downwind from NTS
A survey of death rates from excess cases of childhood leukemia in
Utah from 1944 to 1975 was reported in 1979 (Lyme. Based on preliminary
data on fallout patterns, the state was divided into two parts; counties with
above average and supposedly below average levels of exposure. The
time periods considered were chosen so that there were two "unexposed"
cohorts (deaths occurring before 1951 or in children born after 1958) and
one "exposed" cohort (those under age 15 at any time from 1951 to 1958~.
In the "low-exposure" counties, all three cohorts had mortality rates that
were comparable to the rates for the U.S. population as a whole. In the
'`high-exposure'' counties, the "unexposed" cohorts had rates that were
lower than the rates for the United States as a whole, while the "exposed"
cohort had rates slightly higher than U.S. rates and about 2.4 times higher
than the rates for the "unexposed" cohorts. Land (La79) subsequently
pointed out that death rates for all other childhood cancers in this study
showed the opposite pattern; that is, a lower rate for the "exposed" cohort
OCR for page 374
374 EFFECTS OF EXPOSURE TO LOW LE~LS OF IONIZING MOTION
in the "high exposure" area. This suggested that the apparent increase
in leukemia rates might have been an artifact of diagnostic error. Land
et al. (La84) later reexamined the association, using mortality data from
the National Center for Health Statistics for 1950 to 1978, and found that
while leukemia death rates were about 50% higher in the "exposed" than
in the `'unexposed" cohorts, they were not significantly different at a 90%
confidence level. Moreover, compared to the "unexposed cohort," rates
for eastern Oregon, Iowa, and the total United States were also higher by
about the same amount. Land et al. concluded that there was no pattern of
excess leukemia mortality that supported a causal association with fallout
exposure and that the excess reported reflected an anomalously low rate in
southern Utah during the period 1944 to 1949. Both studies suffer from the
fact that comparisons are based on aggregate groups and may not reflect
any associations among individuals. Futhermore, Beck and Krey (Be83)
have since shown that the levels of fallout were not, in fact, higher in the
"high exposure" counties than in the "low exposure" counties, contrary
to the original supposition. A case-control study is currently in progress
to examine the association between leukemia and individual estimates of
doses, which includes 1,179 patients with leukemia and 5,380 people who
died from other causes among Mormon residents of Utah from 1952 to
1981.
In 1984, Johnson (Jo84) reported on results of a retrospective cohort
study of cancers in Mormon families who were listed in both the 1951 and
1961 telephone directories for towns in southwestern Utah and neighboring
parts of Nevada and Arizona. Self-reports of cancer and other diseases
among those that could be located in 1981 were obtained by volunteers. A
total of 288 cases of cancer were reported in this group, compared with
179 cases of cancer expected on the basis of rates for all Utah Mormons.
The major excesses (observed/expected) were for leukemia (31n.0), thyroid
cancer (20/3.1), breast cancer (35/23.0), melanoma (12/4.5), bone cancer
(8/0.7), and brain tumors (9/3.9~. A subgroup of 239 persons who reported
acute effects from fallout exposure showed even higher rates of cancer (33
cases of cancer at all sites observed compared with 7.1 expected cases).
The cancers reported were not medically confirmed and were likely to
have been overreported; Lyon and Schuman (Ly84) point out that the
female:male ratio was about 70% higher in this study than nationally,
suggesting overreporting of female cases, and that only 126 deaths from all
causes were reported, whereas at least 192 deaths from cancer would have
been expected.
Johnson's reliance on data gathered by volunteers appears to be a
weak point in his study. Machado et al. (Ma87) analyzed cancer rates
from the National Center for Health Statistics for the three counties of
southwestern Utah covered by the survey over the periods 1955-1980 for
OCR for page 375
LOW DOSE EPIDEMIOLOGIC STUDIES
375
leukemia and 1964-1980 for other cancers, and found no excesses of either
single or grouped sites, with the exception of leukemia (62/42.8 for people
of all ages, 9/3.2 for those from 0-14 years old).
Cancer Among Participants in Nuclear Weapons Tests
U. S. Weapons Tests
In 1980, Caldwell et al. (Ca80) reported that among the 3,224 partici-
pants of the nuclear test explosion Smoly, nine cases of leukemia occurred
through 1977, compared with 3.5 expected cases. In a later report (Ca83),
the number of cases of leukemia increased to 10/4.0 and data were provided
on cancer at other sites through 1979. The total number of observed cases
of cancer was 112, compared with 117.5 expected; there was a significant
increase only in leukemia incidence and mortality. In 1984, four cases
of polycythemia Vera were observed, compared with 0.2 expected (Camp.
Robinette et al. (Ro85) expanded the study to include a cohort of 46,186
participants in one or more of five test series at the NTS or the Pacific Prov-
ing Ground (PPG). The excess cases of leukemia among the participants
of the Smoky test were confirmed, but only 46 deaths from leukemia were
observed in the participants of the other PPG tests, compared with 52.4
expected deaths. No one series showed a significant excess of leukemia,
and there was also no consistent excess for any other cancer site.
British Weapons Test
Darby et al. (Da88) described a cohort study of 22,347 British par-
ticipants in nuclear weapons tests and related experimental programs in
Australia and the Pacific Ocean and 22,325 matched controls. For all
causes of death RR = 1.01; for all cancers RR = 0.96. Leukemias and
multiple myeloma occurred significantly more often in participants than
controls; 22 versus 6 cases and 6 versus 0 cases, respectively. However, for
participants at both test sites, the death rates were only slightly higher in
participants than expected, based on national rates (SMR = 113 and 111
respectively), while the death rates were much lower than expected in the
controls (SMR = 32 and 0, respectively). There was no association with
the type or degree of radiation exposure.
Canadian Studies
Raman et al. (Ra87) carried out a cohort study of 954 Canadian military
personnel who had been involved in clean-up operations after nuclear
reactor accidents at ChaLk River Nuclear Laboratories or who had observed
nuclear weapons blasts in the United States or Australia; two matched
controls were selected from military records for each exposed subject. No
OCR for page 376
376 EFFECTS OF EXPOSURE TO LOW LEVELS OF IONIZING EDITION
differences in cause-specific mortality between cases and controls and no
trends by degree of exposure were found; the study size was small, and
only very large differences would have been detectable.
Leukemia from Global Fallout
Archer (Ar87) compared time trends in global fallout across the United
States with trends in leukemia rates. Fallout activity was estimated from
measurements of beta emissions, airborne particulates, precipitation, and
i3iI in milk. Fallout appeared to peak in 1957 and 1962. Death rates for
acute and myeloid leukemia in children aged 5-9 years rose to an initial
peak in 1962 and a secondary peak in 1968; no such pattern was observed
for other types of leukemia. Leukemia death rates (for all ages and all
cell types) peaked in the decade 1960-1969 and were consistently highest in
states with high 90Sr levels in the diet, milk, and bones (based on surveys
by the Public Health Services from 1957 to 1970) and lowest in states with
low 90Sr levels. The excess of myeloid and acute leukemia deaths was
estimated to be about 6.5 per 104 PYGy (based on an estimated average
cumulative dose of 4 mGy).
Darby and Doll (Da87) reviewed data on childhood leukemia incidence
rates and fallout exposures in England and Wales, Norway, and Denmark.
Fallout exposures rose rapidly between 1962 and 1965 and declined slowly
thereafter. In England and Wales there was about a 10% increase in inci-
dence rates up to 1979, possibly attributable to improvements in diagnosis,
whereas incidence rates in Norway and Denmark declined slightly after
1960 during the period of highest population exposure from fallout. The
data were thus interpreted to provide no convincing evidence of an increase
in incidence that could be attributed to fallout.
Summary
There are several possible explanations for the cancer excesses that
have been reported in the studies cited. The possibility that they may
represent chance variations may explain the excess cases of leukemia as-
sociated with the Smoky nuclear test, although that test was unusual in
ways that are discussed below. Chance may also explain the differences in
results from the three studies of leukemia in Utah residents that are based
on reported death rates. Although there appeared to be a small excess
in southwestern Utah, the causality of fallout exposure cannot be assessed
from these studies; the case-control study in progress may help resolve this
uncertainty.
On the other hand, associations may be real and reflect an underesti-
mation either of the doses or of the risk per unit dose. This may be the case
OCR for page 377
LOW DOSE EPIDEMIOLOGIC STUDIES
377
for the Smoly nuclear test, which was the highest-yield tower detonation
at the NTS. Fallout was particularly heavy, 10 to 20 times greater than at
other detonations in this test series (Hasp. The leukemias occurred most
frequently in two groups: those near the hypocenter and those ferried in
by helicopters within hours of the test. Whether these doses could have
been large enough to explain the excess is uncertain.
Although there was a wide variation in individual doses among par-
ticipants at nuclear tests (Ro85), the collective dose could not have been
underestimated sufficiently to explain the excess if the risk coefficients de-
rived from high-dose studies were correct and not underestimated. The
most likely explanation is that the observed excess cases of leukemia are
random overestimates of the risk coefficients. In view of the uncertainty
in both sets of estimates, the discrepancy may be small; Archer's estimate
of the risk coefficient for leukemia based on his data on global fallout is
only slightly higher than that based on data for the atomic-bomb survivors
(Army.
CANCER AMONG INDIVIDUALS NEAR NUCLEAR INSTALLATIONS
Nuclear Reactor Accidents
It is still too early to assess whether any cancer excess will occur
following the Three Mile Island or Chernobyl nuclear reactor accidents.
The collective dose equivalent resulting from the radioactivity released in
the Three Mile Island accident was so low that the estimated number of
excess cancer cases to be expected, if any were to occur, would be negligible
and undetectable (Fable. For the Chernobyl accident, preliminary estimates
suggest that up to 10,000 excess cancer deaths could occur over the next
70 years among the 75 million Soviet citizens exposed to the radioactivity
released during the accident, against a background of 9.5 million cases
of cancer that would occur spontaneously; hence the excess would not be
detectable. However, among the 116,000 people evacuated from immediate
high-exposure areas in the Ukraine and Byelorussia, there might be a
detectable increase in the cases of leukemia and solid cancer (An88, Norm.
Leukemia Among Individuals Near British Nuclear Reprocessing Plants
In the district near the Sellafield nuclear reprocessing plant in northern
England, 6 leukemia deaths in children aged 0-24 years occurred from 1968
to 1974, compared with 1.4 expected cases (Ga84), and 19 incident cases
occurred (10.5 expected) (IAG84~. Follow-up studies of two cohorts, one of
children born to women resident in the Seascale Civil Parish during 1950-
1983 (Ga87a) and one of children born elsewhere but attending schools in
OCR for page 378
378 EFFECTS OF EXPOSURE TO LOW LE~LS OF IONIZING MOTION
Seascale were performed (Ga87b). There were five deaths from leukemia
(0.53 expected) in the former cohort; no deaths were found in the latter
cohort.
Within 12.5 km of Dounreay, a nuclear reprocessing plant in northern
Scotland, five cases of leukemia occurred (0.5 expected) in children of the
same age from 1979 to 1984 (Hemp. Darby and Doll (DaS7) reviewed the
data on radiation exposures in Dounreay and concluded that the excess
cases were not explainable by radioactive discharges from that nuclear
installation. Recently, the influx of a large number of new workers with a
concomitant increase in viral infections has been proposed as a causative
factor for childhood leukemia in Dounreay and Sellafield (Kings.
Cancer Among Individuals Near Other Nuclear Installations
Roman et al. (Ro87) described a cluster of 29 cases of leukemia
(14.4 expected) in children aged 0-4 years living within 10 km of one
or more nuclear facilities in southern England. Hole and Gillis (Ho86)
reported a cluster of 31 cases of leukemia (24.3 expected) in children aged
0-14 years living in regions adjacent to four nuclear facilities in western
Scotland. These reports are difficult to interpret, owing to the bias due
to first observing an apparent cluster and then defining the population
at risk and the time period of risk. ~ avoid this bias, Baron (Ba84)
examined cancer mortality in individuals living near 14 nuclear and 5
nonnuclear facilities in England and Wales and found no overall pattern of
increasing cancer SMRs in individuals living around the nuclear facilities. A
more comprehensive survey of cancer incidence and mortality near nuclear
installations for the period 1959-1980 is reported by the United Kingdom
Office of Population Censuses and Surveys (Co87a, Foam. The investigators
found significant overall excesses of cancer mortality due to lymphoid
leukemia and brain cancer in children and due to liver cancer, lung cancer,
Hodgkin's disease, all lymphomas, unspecified brain and central nervous
system tumors, and all malignancies in adults; however, the mortality rates
in the control areas were lower than expected, and there has not been a
general increase in cancer rates in individuals living in the vicinity of nuclear
installations. Moreover, there were no consistent, positive, or statistically
significant trends in cancer rates with distance from the nuclear installations.
Beral (Be87) noted that the incidence of leukemia and all cancers in
children were significantly elevated in all exposed areas combined (excluding
Sellafield) compared with those in control areas, whereas mortality was not.
Cook-Mozaffari (Co87) confirmed the observation, but suggested that the
differences may be due to a variation in case registration, possibly owing
to social class differences.
Recently, Openshaw et al. have demonstrated how cancer clusters
OCR for page 379
LOW DOSE EPIDEMIOLOGIC STUDIES
379
can be identified objectively using a Geographic Analysis Machine (Op88).
This methodology was applied to mortality data for acute lymphoblastic
leukemia in children living in the Northern and Northwestern regions of
England. Again, Seascale, near Sellafield, in Cumbria was identified as
an area having unusually high mortality. Although this type of analysis
requires a large computational effort, it appears to free studies of cancer
clusters from bias due to the selection of an arbitrary risk area and the
effects of arbitrary administrative Foundries.
Clapp et al. (C187) reported excess cases of leukemia and other hema-
tologic malignancies in five Massachusetts towns located near a nuclear
reactor. There were 13 excess cases of myelogenous leukemia in males
(5.2 expected); the excess cases were mainly in adults, and the possible
confounding effect of occupational factors was not considered.
No excess cases of cancer have been found around either the Rocky
Flats nuclear reprocessing plant in Colorado (Cr87) or the San Onofre
nuclear power plant in California (Entry.
Summary
It is difficult to assess the significance of the reports of excess cancer
cases near nuclear installations in Great Britain; it appears highly unlikely
that all were caused by chance, although the anecdotal nature of some of the
observations makes testing of significance impossible. Available radiation
dosimetry information also makes it seem unlikely that the excesses or
clusters could be explained by the very low radiation exposures. While
there has not been a general increase in cancer rates in individuals living
in the vicinity of nuclear installations (Co87a,b, Fo87), there does appear
to be an excess in the number of cases of childhood leukemia, particularly
in individuals living around installations before 1955 and among children
born in the region. Whether the excesses will be found to be balanced by
a comparable number of deficiences around other nuclear installations, or
whether they will prove to occur more consistently than not, are questions
calling for further study.
EPIDEMIOLOGIC STUDIES OF WORKERS EXPOSED TO LOW DOSE,
LOW-LET RADL\TION
A number of epidemiologic studies of individuals exposed occupation-
ally to low levels of low-LET radiation have been reported. Although,
because of limited size and exposure, such studies cannot contribute di-
rectly to the estimation of stable radiation risk estimates, they are of
use for assessing whether such estimates are substantially in error. Oc-
cupational studies have several noteworthy advantages and disadvantages.
OCR for page 380
380 EFFECTS OF EXPOSURE TO LOW LEVELS OF IONIZING MOTION
Occupational exposures are generally monitored, but there may still remain
considerable uncertainty about exposures measured in early years (see for
example Inept. Also there may be multiple exposures both to external
sources and internal emitters of radiation, and to many potentially carcino-
genic chemicals, which may make any specific radiation effect difficult to
isolate. Occupational cohorts are usually well defined and their individual
members well identified, which facilitates follow-up, but the healthy worker
effect the tendency for working populations to have lower rates of mor-
tality than those of the general population, primarily because of selection
factors-means that comparisons between an occupational cohort and the
general population can be difficult to interpret.
Epidemiologic Studies of Workers
Table 7-1 summarizes the available details on those occupational stud-
ies that have been published to date. In these studies, workers were
monitored for their exposure to low-LET ionizing radiation. The power of
such studies to detect a significant increase in risk depends on the number
of observed deaths from the cause of interest. Several of these studies
have yet to accumulate a sufficient number of deaths to reach any sensible
conclusions relating to individual types of cancer. The most consistent
result, observed to date from the studies shown in Table 7-1, is that the risk
estimates for all types of cancer combined and for all types of leukemia
combined are consistent with the risk estimates provided in the present
report, since no studies have reported results which differ significantly from
the null. In terms of individual cancers, a significant and dose-related ef-
fect has been observed for multiple myelomas in the Hanford study (Gi89)
and in the British Nuclear Fuels study (Smash; in the latter case, data
from individuals who received the dose 15 years before death are excluded.
A significant excess of prostate cancer has been observed in the United
Kingdom Atomic Energy Authority study (Be85), but this excess seems
to be associated, in part, with exposures to multiple forms of radiation,
including tritium and other internal nuclides. Excesses of prostate cancer
were also seen in the British Nuclear Fuels and the Oak Ridge National
Laboratory studies (Ch85), but these excesses were not significant and were
not dose related. In addition to multiple myelomas and prostate cancer,
dose-response effects as a result of exposure to external gamma radiation
have been reported for bladder cancer and all lymphatic and hematopoietic
cancers by the British Nuclear Fuels study (doses received in the 15 years
prior to death are excluded), and for lung cancer by the Oak Ridge Y-12
Plant study (Cheat. In the latter study, part of the dose to the lung was
due to alpha radiation.
OCR for page 381
381
o ~
.
o ~
z a
~ _
~2 uo
O ~
am
o
._
._
Cal
-
C~
in:
x
o
is
o
._
o
V)
hi
o
3
o
V)
. _
4-
Cal
. _
o
-
o
._
~5
._
o
Cal
m
EM
C .= ~
C ~ C
;~
C ~ I.
C
7 ~ ~
~ ~ ._
V)
~ A_
~ C
·( <)
r - ,
~_
hi
- , Ha
-
_
U)
C)
_ _
Cat ~
',
X X
r - . ~
. ~
-
-
lo.
_ ,
_ ~
TIC
_ _
v, ~v, cat ~ a)
- ~ G.> ~ -
_ · Ct ~ ~
- ~t X tr~- £
-)
~x
c
c
=
c
au
£
0 ~
v-, _
~ £
t-_ c
c Cx5
G ~
;,` G
~ O
C ~C ~X ~
~_ _ _
~X C~
r~
_ _ _ _
~I
_ _ _ _
C U ~ O ' C ~U ~C
D -' - D ~V o ° U C ~
D~ - · . W o ~ _ A
~ '~ C ~C: t~
D o - u ^O _ Z C -
~v/ _ ~ 3 u ~a u
m ~O
OCR for page 382
382
s
.~
a,
-
_ o ~
Em Z ~
~ _
an ~
cat vet
o
ox o
z ~ 3
V)
=> == E E
O ~ v'
is c:.=
3
a
To
v,
en ~d
~ 0
0 ~
ILL cL
~ O
0 ~
oo ~on
ED
or
a
x
cat
.. ~
~ ~ vat
~ \c, an
x ~ x ~
_`
. vet
~ -
_
cot
ED
x
x . cot ~
~ ~0
. . ~ ~ ~
vat
v,
a'
oo
cat
0
~ 0
v~
c~
. _
v' c~
~ a~
_ _
~; ~;
r~
o~
r
cr ~v~
~oo oo
~_. ~
v~
x oo
o ~
II 0 ~
~cr o ~
_.
v, 4
c ~
J o ~r-i=,, Ct C c.~ O O
E _ _ ~ ·= ·= 0 ~ 0
c,3 ~A ~ e ° ° - ~r~°
~ c ~ ~ c <: E c c ~ c
O ,. ~ ~O
v:
_ ~
cr ~
~0
-
3
oo
l
oo
0
0 ~ ~
~ 0 ~
`, 3 .=
:=
au ~ ~
o3 .
O
0 0 ~ I
~ ~ c~ ~
°=,£= ~
~ oc ~ 0
~ ~ ~ ed
~ c., ~ ~
._ _ ~ ~
3 ~ o~
3
0
. ~ e~ ~
O ~ ~ D
Z ~ ~ O
V,
a
OCR for page 383
LOW DOSE EPIDEMIOLOGIC STUDIES
Summary
383
The studies have provided no evidence to date that risk estimates
for leukemias and other types of cancer combined are in error, based
on extrapolation from high-dose studies. For individual cancer sites, only
for multiple myelomas and prostate cancer is there any suggestion that
associations were seen in more than one study. In interpreting the latter
associations, however, the potential biases discussed in Chapter 1 must
be borne in mind. In particular, the problem of multiple comparisons
and the tendency for both researchers and editors to focus on positive
as opposed to null results. It must also be pointed out that the absence
of any associations in a number of studies essentially offers no meaningful
evidence, because of the very small numbers of observed deaths. Continued
monitoring of these and other occupational cohorts in the future is highly
desirable. When possible, standardization and pooling of study results
should improve the interpretation and the overall significance of these
studies. 1b date the evidence does not contradict or imply the possible
inaccuracy of risk estimates derived from high-dose studies.
HIGH NATURAL BACKGROUND RADIATION
There are regions in the world where outdoor terrestrial background
gamma radiation levels appreciably exceed the normal range (about 0.2-0.6
mGy per year). Such regions exist in Brazil, India, People's Republic of
China, Italy, France, Iran, Madagascar, and Nigeria (UNTO. Because the
total dose rate of low-LET natural background radiation is low, and the
lifetime dose of such radiation accumulated by any one person is small
(<0.1 Gy), it is difficult to determine whether there are any variations in
disease rates associated with changes in natural background radiation levels
and, if so, whether such variations are consistent with the health effects
estimated by extrapolation from the observed effects of high-dose and high
dose-rate exposures.
A cautious approach is warranted in the interpretation of geograph-
ically based mortality surveys. Although "beneficial" effects of radiation
have been alleged on the basis of reduced mortality in high background
areas in the United States (Hi81), analyses that include an adjustment for
altitude indicate no "beneficial" effects (Weary. While mortality rates for
both cancer and cardiovascular disease are lower in areas of the United
States having high levels of natural radiation, such areas are found primarily
in high altitude locations. This apparently "beneficial" effect of radiation
may, in fact, be an example of confounding, since conditions of reduced
oxygen pressure stimulate a wide array of physiological adaptations, which
could themselves be protective (Froth.
OCR for page 384
384 EFFECTS OF EXPOSURE TO LOW LE~LS OF IONIZING IDEATION
Recently, childhood cancers have been analyzed in relation to natural
radiation levels in England (Kn88), and although reported associations
were observed, their interpretation is complicated by the general problems
of correlational analyses (see Chapter 1, Epidemiological Principles).
Guarapari, Brazil
This village of approximately 12,000 inhabitants is located in an area
where local soil contains monazite sands, which is the source of gamma and
alpha radiation received by the townspeople. The radioactivity in monazite
comes primarily from thorium. The average annual absorbed dose to an
inhabitant of this area, based on lithium fluoride dosimetry, is about 6.4
mSv (640 mrem), which is roughly 6 times the global average background
radiation dose level (excluding radon progeny in the lung) (Bagel. Studies
of the health of this population are limited, but a cytogenetic study of
200 individuals, in comparison with a control group from a similar vil-
lage, reported an increase in the total number of chromosome aberrations
(Baby.
Kerala, India
The population living along the Kerala Coast of India is exposed to
about 4 times the normal level of natural background radiation (excluding
radon progeny in the lung). Because of the presence of monazite in the
soil (thorium concentration, 8.0-10.5%, by weight), the average absorbed
dose rate for the 70,000 people living in the region has been estimated to
be about 3.8 mGy/yr (380 mrad/yr) (Going. The incidence of both Down
syndrome and chromosome aberrations has been reported to be increased
in this population (Kook.
YanjIang County, Guangdong Province, Peoplets Republic of China
The most extensive observations on the health effects of high natural
background radiation have been those made on the mortality experience
of the population in Guangdong Province, People's Republic of China. In
this area, which contains monazite with high levels of thorium, uranium
and radium, individuals are exposed to about 3-4 mSv (300-400 mrem)
of gamma radiation per year. The population of this region has been
studied extensively for both genetic and carcinogenic effects (We86, Ta86~.
A sample of 70,000 individuals in this area and a geographically adjacent
control area, receiving a normal background of radiation of 1 mSv/year (100
mrem/year), were followed for the period 1970-1985, with approximately 1
million person-years of follow-up in each area.
OCR for page 385
LOW DOSE EPIDEMIOLOGIC STUDIES
385
On analysis, site-specific, age-adjusted cancer mortality rates did not
differ between the high natural background area and the control area. For
total cancer mortality, the observed cancer rate was higher in the normal
background area, although the difference was not statistically significant.
Known risk factors affecting cancer mortality rates were generally compa-
rable in the two areas, although there were some cultural and educational
differences. Chromosome aberrations and a higher reactivity of T lympho-
cytes were found in individuals in the high natural background area. There
were no differences for a large number of hereditary diseases or congenital
defects in children. The prevalence of Down syndrome was greater in the
high-background region, but this was discounted because the residents of
the control area had a lower prevalence of Down syndrome than those
of surrounding counties, who had rates similar to those living in the high
natural background area.
Summary
In areas of high natural background radiation, an increased frequency
of chromosome aberrations has been noted repeatedly. The increases are
consistent with those seen in radiation workers and in persons exposed at
high dose levels, although the magnitudes of the increases are somewhat
larger than predicted. No increase in the frequency of cancer has been
documented in populations residing in areas of high natural background
radiation.
REFERENCES
An86
An88
Ar87
Ay84
Ba75
Ba84
Be83
Be85
Anderson, T. W. 1986. Ontario Hydro Modality 1970-1985. Ontario Hydra
Report, Canada.
Anspaugh, Lo R., R. J. Catlin, and M. Goldman. 1988. Ibe global impact of
the Chernobyl reactor accident. Science 242:1513-1519.
Archer, V. E. 1987. Association of nuclear fallout with leukemia in the United
States. Arch. Environ. Health 42:263-271.
Ayesh, R., J. R. Idle, J. C. Ritchie, M. J. Crothers, and M. R. Hetzel. 1984.
Metabolic oxidation phenotypes as markers for susceptibility to lung cancer.
Nature 312:169-170.
Barcinski, M. A., M. D. C. ~ Abreu, J. C. C. De Almeida, J. M. Naya, L.
G. Fonseca, and L. E. Castro. 1975. Cytogenetie investigation in a Brazilian
population living in an area of high natural radioactivity. Am. J. Hum. Genet.
27:802-806.
Baron, J. A. 1984. Cancer mortality in small areas around nuclear facilities in
England and Wales. Br. J. Cancer 50:815-829.
Beck, H. L., and P. W. Krey. 1983. Radiation exposure in Utah from Nevada
nuclear tests. Science 220:18-24.
Beral, V., H. Inskip, P. Fraser et al. 1985. Modality of employees of the United
Kingdom Atomic Energy Authority, 1946-1979. Br. Med. J. 291:440-447.
OCR for page 386
386 EFFECTS OF EXPOSURE TO LOW LE^LS OF IONIZING MOTION
Be87
Ca80
Ca84
Ch85
Ch88
Cl87
Co87a
Co87b
Cr87
Da87
Da88
En83
Ev86
Fa81
Beral, V. 1987. Cancer near nuclear installations (letter). Lancet i:556.
Caldwell, G. S., D. B. Kelley, and C. W. Heath. 1980. Leukemia among
participants in military maneuvers at a nuclear bomb test: A preliminary
report. J. Am. Med. Assoc. 244:1575-1578.
Caldwell G. G., D. Kelley, M. Zack, H. Falk, and C. W. Heath. 1983. Mortality
and cancer frequency among military nuclear test (Smoky) participants, 1957
through 1979. J. Am. Med. Assoc. 250~5~:620-624.
Caldwell, G. C., D. B. Kelley, C. W. Heath, Jr., and M. Zack. 1984.
Polycythemia Vera among participants of a nuclear weapons test. J. Am.
Med. Assoc. 252:662-664.
Checkoway, H., R. M. Mathew, C. M. Shy, et al. 1985. Radiation, work
experience, and cause specific mortality among workers at an energy research
laboratory. Br. J. Ind. Med. 42:525-533.
Checkoway H., N. Pearce, D. J. Crawford-Brown, et al. 1988. Radiation doses
and cause specific mortality among workers at a nuclear materials fabrication
plant. Am. J. Epidemiol. 127:255-266.
Clapp, R. W., S. Cobb, C. K. Chan, and B. Walker, Jr. 1987. Leukaemia near
Massachusetts nuclear power plant. Lancet ii:1324-1325.
Cook-Mozaffari, P., F. Lo Ashwood, T. Vincent, et al. 1987. Cancer incidence
and mortality in the vicinity of nuclear installations. England and Wales,
1950-1980. Studies on Medical and Population Subjects, No. 51. London: Her
Majesty's Stationery Office.
Cook-Mozaffari, P. 1987. Cancer near nuclear installations (letter). Lancet
i:855-856.
Crump, K. S., T. H. Ng, and R. G. Cuddihy. 1987. Cancer incidence patterns
in the Denver metropolitan area in relation to the Rocky Flats plant. Am. J.
Epidemiol. 126(1):127-135.
Darby, S. C., and R. Doll. 1987. Fallout, radiation doses near Dounreay, and
childhood leukemia. Br. Med. J. 294:603-607.
Darby, S. C., G. M. Kendall, T. P. Fell, et al. 1988. A summary of mortality
and incidence of cancer in men from the United Kingdom who participated
in the United Kingdom's atmospheric nuclear weapon tests and experimental
programs. Br. Med. J. 296:332-338.
Enstrom, J. E. 1983. Cancer mortality patterns around the San OnoEre nuclear
power plant, 1960-1978. Am. J. Public Health 73~1~:83-92.
Evans, J. S., J. E. Wennberg, and B. J. McNeil. 1986. The influence of
diagnostic radiography on the incidence of breast cancer and leukemia. N.
Engl. J. Med. 315:810-815.
Fabrikant, J. I. 1981. Health effects of the nuclear accident at Three Mile
Island. Health Phys. 40:151-161.
Fo87 Forman, D., P. Cook-Mozaffari, S. Dark et al. 1987. Cancer near nuclear
installations. Nature 329:499-505.
Fraisancho, A. R. 1975. Functional adaptation to high altitude hypoxia. Science
187:313-319.
Fallout Study Group. 1988. A case-control study of leukemia in Utah and its
relationship to fallout from nuclear weapons testing. Unpublished manuscript.
Gardner, M. J., and P. D. Winter. 1984. Mortality in Cumberland during
1959-78 with reference to cancer in young people around W'ndscale (letter).
Lancet i:216-217.
Gardner, M. J., ~ J. Hall, S. Downes, and J. D. Terrell. 1987. Follow up
Fr75
FSGS8
Ga84
Ga87a
OCR for page 387
LOW DOSE EPIDEMIOLOGIC STUDIES
Ga87b
387
study of children born to mothers resident in Seascale, West Cumbria (birth
cohort). Br. Med. J. 295:822-827.
Gardner, M. J., A. J. Hall, S. Downes, and J. D. Terrell. 1987. Follow up study
of children born elsewhere but attending schools in Seascale, West Cumbria
(schools cohort). Br. Med. J. 295:819-822.
Gi72 Gibson, R., S. Graham, A. Lilienfeld, L. Schuman, J. E. Dowd, and M. L.
Levin. 1972. Irradiation in the epidemiology of leukemia among adults. J.
Natl. Cancer Inst. 48:301-311.
Gilbert, E. S., J. G. R. Petersen, and J. A. Buchanan. 1989. Mortality of
workers at the Hanford site: 1945-1981. Health Phys. (in press).
Gopal-Ayengar, A. R., K. Sundaram, K. B. Mistry, C. M. Sunta, K. S. V. Nambi,
S. P. Kathuria, A. S. Basu, and M. David. 1971. Evaluation of the long-term
Effects of high background radiation on selected population groups on the
Kerala Coast. Pp. 31-51 in Proceedings of the 4th International Conference
on Peaceful Uses of Atomic Energy, Vol. 11.
Gunz, F., and H. Atkinson. 1964. Medical radiation and leukemia: A
retrospective survey. Br. Med. J. 1:389.
Harris, P. S., C. Lowery, A. G. Nelson, S. Obermiller, W. J. Ozeroff, and E.
Weary. 1981. Shot Smoky, a test of the Plumbob Series, 31 August, 1957.
Technical Report DNA 6004F. Washington, D.C.: Defense Nuclear Agency.
Heasman, M. A., I. W. Kemp, J. D. Urquhart, and R. Black. 1986. Childhood
leukaemia in northern Scotland (letter). Lancet i:266.
Hi81 Hickey, R. J., E. J. Bowers, D. E. Spence, B. S. Zemel, A. B. Clelland,
and R. C. Clelland. 1981. Low level ionizing radiation and human mortality:
Multiregional epidemiological studies. Health Phys. 40:625~41.
Hickey, R. J., E. J. Bowers, D. E. Spence, B. S. Zeuill, A. B. Cleland,
and R. C Cleland. 1987. Low level ionizing radiation and human mortality:
multiregional epidemiological studies. Health Phys. 40:625-641.
Hole, D. J., and C. R. Gillis. 1986. Childhood leukemia in the west of
Scotland. Lancet 2:525-525.
Howe, G. R., J. L. Weeks, A. B. Miller, et al. 1987. A follow-up study of
Gi89
Go71
Gu64
Ha81
He86
Hi87
Ho86
Ho87
IAG84
In86
In87
Jo84
Ki88
Kn88
radiation workers employed by Atomic hnergy of Canada Limited: Mortality,
1950-1981.
Independent Advisory Group. 1984. Investigation of the possible increased
inriden~. of ~ncer in West Cumbria. London: Her Majesty's Stationery OffirW.
Interlaboratory Task Group on Health and Environmental Aspects of the Soviet
Nuclear Accident. June 1987. Health and Environmental Consequences of
the Chernobyl Nuclear Power Plant Accident. DOE/ER-0332. Springfield, Va.:
National Technical Information Sewice.
Inskip, H., V. Beral. P. Fraser. et al. 1987. Further assessment of the effects
..._. ~ _.. w _ _
of occupational radiation exposure in the United Kingdom Atomic Energy
Authority mortality study. Br. J. Ind. Med. 44:149-160.
Johnson, C. J. 1984. Cancer incidence in an area of radioactive fallout
downwind from the Nevada test site. J. Am. Med. Assoc. 251:230-136.
Kinlen, L. 1988. Evidence for an infective cause of childhood leukemia:
comparison of a Scottish new town with nuclear reprocessing sites in Britain.
Lancet ii:1323-1326.
Knox, E. G., A. M. Stewart, E. A. Gilman, and G. W. Kneale. 1988.
Background radiation and childhood cancer. J. Radiol. Prot. 8~1~:9-18.
OCR for page 388
388 EFFECTS OF ENSUE TO LOW LE~LS OF IONIZING IDEATION
Ko76
La79
La84
Li80
Ly79
Ly84
Ma87
NRC80
No86
Op88
Pi83
Pr88
Ra87
Ro84
Ro85
Ro87
Sh86
Sm86
St62
Koehupillan, N., I. C. Verma, M. S. Grewal, and V. Ramalingaswami. 1976.
Down's syndrome and related abnormalities in an area of high background
radiation in coastal Kerala. Nature 262:60-61.
Land, C. E. 1979. The hazards of fallout or of epidemiologic research. N.
Engl. J. Med. 300:431-432.
Land, C. E., F. W. McKay, and S. G. Machado. 1984. Childhood leukemia
and fallout from the Nevada nuclear tests. Science 223:139-144.
Linos, A., J. Gray, A. Orvis, et al. 1980. Low dose radiation and leukemia.
N. Engl. J. Med. 302:1101.
Lyon, J. K, M. R. Klauber, J. Hi! Gardner, and K. S. Udall. 1979. Childhood
leukemias associated with fallout from nuclear testing. N. Engl. J. Med.
300:397-402.
Lyon, J. L., and K. L. Schuman. 1984. Radioactive fallout and cancer (letter).
J. Am. Med. Assoe. 252~14~:1854-1855.
Maehado, S. G., C. E. Land, and F. W. McKay. 1987. Cancer mortality and
radioactive fallout in southwestern Utah. Am. J. Epidemiol. 125:44-61.
National Research Council, Committee on the Biological Effects of Ionizing
Radiations. 1980. The Effect on Populations of Exposure to Low Levels of
Ionizing Radiation (BEIR III). Washington, D.C.: National Academy Press.
524 pp.
Norman C., and D. Dickson. 1986. The aftermath of Chernobyl. Seienee
223:1141-1143.
Openshaw, S., M. Charlton, A. W. Craft, and J. M. Birch. 1988. Investigation of
leukemia clusters by use of a geographical analysis machine. Lancet i:272-273.
Pickle, L. W., L. M. Brown, and W. J. Blot. 1983. Information available from
surrogate respondents in case-control interview studies. Am. J. Epidemiol.
118:99.
Preston-Martin, S., D. C. Thomas, M. C. Yu, and B. E. Henderson. Submitted.
Diagnostic radiography as a risk factor for chronic myeloid leukemia.
Raman, S., G. S. Dulberg, R. A. Spasoff, and T. Scott. 1987. Mortality among
Canadian military personnel exposed to low dose radiation. Can. Med. Assoe.
J. 136:1051-1056.
Rowley, J. B. 1984. Biological implications of consistent chromosome rear-
rangements in leukemia and Iymphoma. Cancer Res. 44:3159-3168.
Robinette, C. D., S. Jablon, and T. L. Preston. 1985. Studies of participants
in nuclear tests. Washington, D.C.: National Research Council.
Roman, E., V. Beral, L. Carpenter, et al. 1987. Childhood leukaemia in
the West Berkshire and Basingstoke and North Hampshire District Health
Authorities in relation to nuclear establishments in the vicinity. Br. Med. J.
294:597-602.
Shrimpton, P. C., B. F. Wall, D. G. Jones, E. S. Fisher, M. C. Hillier, G. M.
Kendall, and R. M. Harrison. 1986. Doses to patients from routine diagnostic
x-ray examinations in England. Br. J. Radiol. 59:749-758.
Smith, P. G., and A. J. Douglas. 1986. Mortality of workers at the Sellafield
plant of British Nuclear Fuels. Br. Med. J. 293:845-854.
Stewart, A., W. Pennypaeker, and R. Barber. 1962. Adult leukemia and
diagnostic x-rays. Br. Med. J. 2:882.
Stewart, A. 1973. An epidemiologist takes a look at radiation risks. DHEW
Publ. No. [FDA] 738024, BRH/DBE 73-2. Washington, D.C.: U.S. Department
of Health, Education, and Welfare.
OCR for page 389
LOW DOSE EPIDEMIOLOGIC STUDIES
St73b
1586
UN82
We86
Wl87
389
Stewart, A. 1973. The carcinogenic effects of low level radiation. A re-appraisal
of epidemiologic methods and observations. Health Phys. 24:223-240.
Tao, Z., and L. Wei. 1986. An epidemiological investigation of mutational
diseases in the high background radiation area of Yangjiang, China. J. Radiat.
Res. 27:141-150.
United Nations Scientific Committee on the Effects of Atomic Radiations
(UNSCEAR). 1982. Ionizing Radiation: Souces and Biological Effects. United
Nations publication. E.82.IX.8 06300p. New York: United Nations, 773 pp.
Wei, L. X, Y. R. Zha, Z. F. Tao, et al. 1986. Recent advances of health
survey in high background areas in Yangjiang, China. Pp. 1-17 in Proceedings
of the International Symposium on Biological Effects of Low Level Radiation.
Wilkinson, G.S., G. L. Tietjen, L. D. Riggs, W. A. Galke, J. F. Acquavella, M.
Reyes, G. L. Voelz, and R. J. Waxweiler. 1987. Mortality among plutonium
and other radiation workers at a plutonium weapons facility. Am. J. Epidemiol.
125:231-250.
OCR for page 390
Representative terms from entire chapter:
natural background
