see the blast, some misclassification of
exposure status is possible, since they
would not have had the personal experience of this dramatic event to date their
1954 atoll of residence. However, if such
persons incorrectly recalled their location in 1954, the error would have probably been another southern atoll, since
they would likely have remembered the
BRAVOtest had they lived on a northern atoll. In addition, transportation to
and from theseislands in the 1950s was
not frequent, so the likelihood of misclassifying exposure remains small.
Theissue ofmultiple exposuresarises
in this study population since there
were 66 announced nuclear tests in the
Marshall Islands between 1946 and

1958. Many of these tests,“ however,

took place on Eniwetok Atoll, which is
located about 200 miles west of Bikini.
In addition, most of these tests were
conducted when the prevailing winds
were heading away from the Marshall
Islands. More importantly, the BRAVO
test was the largest of the 66 nuclear
tests; it is the only test that people on
distant atolls recall having seen. Thus,
while it is possible that atolls close to
Bikini, such as Rongelap, may have
been exposed on multiple occasions,itis
unlikely that such exposure occurred on
distant atolls.
Because this study was a retrospective cohort design, the important issue
of latency cannot be addressed. Prospective studies of the Rongelap and
Utrik populations reported a mean latency for thyroid nodules of 13 years for
Rongelap children exposed at ages less
than 10 years. The Utrik children, with
lower thyroid doses, had a mean latency
of 25 years. Whether persons exposed
to smalier doses in the present study
may exhibit even longer latent periods
is unknown.Since latent periodsat least
as long as 34 years are thoughtto exist
in other populations exposed to thyroid
irradiation,” it will be necessary to
continue close follow-up of this population.
Theresults of this study suggest that
the northern atolls used in previous
studies as a source for unexposed controls, with a prevalence of nodules of
6.3%, were inappropriately selected,
since the prevalence in our study continues to decrease to less than 1% for the
southern atolls, which are located the

farthest from the Bikini test site. We
believe that a better estimate of the
prevalence of thyroid nodules in unexposed Marshallese is 2.45%, the mean
prevalence of the two southernmost
atolls. Since the prevalence continues to
decrease to a value less than 1% for the
atoll farthest from the blast site, 2.45%
is probably a conservative estimate for
the spontaneous or backgroundrate of
solitary thyroid nodules in the Marshall
Islands.
Because authors of previous studies
used the prevalence of 6.3% for presumably unexposed controls, their risk co-

efficient of 830 excess cases/Gy/y/1 x 10°

persons (8.3 excess cases/rad/y/1 million

persons)” underestimatesthe truerisk.
Using our estimate of 2.45% for the
prevalence of nodules in unexposed
Marshallese, our new risk coefficient is
1100 excess cases/Gy/y/1x10° persons
(11.0 excess cases/rad/y/1 million persons). This is 33% higher than the previous estimate and is quite close to a
published composite estimate of 12.3

(1230) for gamma radiation.”

The components of radiation dose to
the thyroid gland in Marshall Islanders
exposedto fallout are relatively unique
amongstudies of humansin whom thyroid neoplasia has developed from ionizing radiation. While gamma radiation
accounts for part of the total thyroid
dose in the Marshall Islands exposure
(4% to 16%), the majority of the thyroid
dose came from the short-lived radioiodines, “I, “I, and ™I, and, to a lesser
extent, "I." There islittle information
in the literature, other than that from
exposures in the Marshall Islands, concerning the effects of these radioiodines
in humans. Although “I alone is known
to induce thyroid neoplasms in animal
studies,“ it is much less effective in
the induction of human thyroid neoplasms, possibly 50 times less so than
gammairradiation.” Indeed, studies of
*1I therapy in Graves’ disease have led
to doubts about whether “I alone induces thyroid nodules in humans.***?”
One explanation for the ineffectiveness
of “I as a carcinogen in these studies
may be that autoimmune thyroid disease renders the thyroid glandresistant
to the developmentof neoplasms from
“T irradiation. An additional factor
is the nonuniform distribution of “I
within thyroid tissue compared with

gammaradiation; the dose from this
type of distribution can ablate tissue at
localized “hot spots” and result in a
lower dose to the remaining thyroid
tissue. Other explanations include the
lower dose rate of beta-emitting I
compared with gamma radiation and
the decreased potential of the thyroid
gland to undergo malignant transformation once ablative doses of “I have
been received by the entire gland.®
However, while the role of “I as an
inducer of thyroid neoplasia remains
controversial, it should be emphasized
that radioiodine fallout contains not
only “I but a mixture of short-lived,
higher-energy radioiodines.
The public health implications of
these results are important not only to
the Marshallese people but also to populations that may be exposed to shortlived radioiodines from fallout such
as may occur during nuclear reactor accidents. These isotopes include the
higher energy beta-emitters I, “I,
and “I and do appear to be effective inducers of thyroid nodules. In our study,
we found the absolute risk coefficient to
be nearly identical to the estimate for
gammairradiation. Thus, populations
exposed to radioiodine fallout should
not only be considered for potassium
iodide prophylaxis at the time of contamination but should also be carefully
followed up for the late development of
thyroid nodules. We anticipate the expected rates of such neoplasms to be
similar to those found from gammaradiation.
The field work for this study was supported by
the Marshall Islands Atomic Testing Litigation
Project, Los Angeles. The analysis and preparation
of this manuscript was supported in part by a grant
from the Robert Wood Johnson Foundation, Princeton, NJ.
We are indebted to the following Marshallese
field staff: Staff Director Atra Lang, Leilani Lokboj, Julie Lloyd, Winnie MacQuinn, Aida Nashion,
Anibar Timothy, and Lijon Eknilang. Special gratitude is expressed for the cooperation of the people
of the Marshall Islands, the loca] council governments on the atolls, Minister of Health Dr Jeton
Anjain (1982), representatives of the Republic of the
Marshall Islands, and to all members of the Mar-

shall Islands Atomic Testing Litigation Project. We
are also indebted to Robert Griep, MD, and Lori
Bernstein for participation in the validation aspects

of this study; to Bruce Psaty, MD, MPH, Tom
Koepsell, MD, MPH, and Linda Rosenstock, MD,
MPH, for critical review of the manuscript; to Mary
Miller for assistance in data abstraction; and to
Paulette Gilliam for preparation of the manuscript. |

References
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JAMA,Aug 7, 1987—Vol 258, No. 5

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3. Conard RA, Knudsen KD, Dobyns BM, et al: A
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4. Conard RA, Sutow WW, Lowrey A, et al:
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