Acute Leukemias - Republican Scientific Medical Library

a 5.3 · Etiology 85
tern of ALL diagnosis or symptoms. Karimi and Yarmohammadi
found a late fall, early winter peak in Iran,
Sorensen et al. [138] a fall peak in Denmark, Higgins
et al. [44], Westerbeek et al. [157] and Badrinath et al.
[7] summer peaks in Europe, and Ross and colleagues
[123] a summer peak in the northern USA, with approximately
a 7.5% excess over the mean in July and August.
This suggests a possible link to allergic and infections
processes in the summer that may trigger the ALL
disease process, although further research is needed to
more precisely define this effect.
5.3.2 Physical Factors
5.3.2.1 Ionizing Radiation
The importance of ionizing radiation as an etiologic
agent for leukemia and other lymphohematopoeitic
cancers has been known since the early 1900s from
studies of radiologists [8]. However, the most compelling
evidence for this association has come from studies
of survivors of the atomic bomb blasts in Hiroshima
and Nagasaki [107] and patients treated for ankylosing
spondylitis [20]. For both of these types of exposures,
leukemias (other than chronic lymphocytic) were noted
as early as 3 years after exposure, with peak incidence
occurring 5–10 years after exposure, and additional
cases were diagnosed even 30 years after exposure
[60]. For ankylosing spondylitis, the strongest effect
was for AML rather than ALL.
There also is evidence for leukemia risk associated
with occupational exposure to ionizing radiation among
those involved with the nuclear industry [75]. Studies of
military personnel on maneuvers at a nuclear bomb test
showed statistically elevated leukemia incidence and
mortality [96], as do the most recent studies of workers
at other nuclear facilities. A review and pooled analysis
of nuclear worker studies conducted by the International
Agency for Research on Cancer (IARC) found statistically
significant excess relative risks for leukemia
excluding chronic lymphocytic leukemia [14]. The leukemia
exposure-response effect was consistent with
but smaller than the values estimated from the studies
atomic bomb survivors reported in the BEIR V report
from the National Research Council [97]. Studies of
workers at naval nuclear shipyards are inconsistent,
while studies of fallout from bomb testing showed small
increases in cases of leukemia [33], particularly acute
leukemias among children, although the interpretations
of these data vary [67, 82, 84, 143].
Prenatal exposures are also a concern. In the 1950s, a
British study showed that radiography of a pregnant
woman’s abdomen increased the child’s risk of leukemia
by about 50% [144]. While this relationship is believed
to be causal, few women today undergo this type of diagnostic
testing, making this a nonissue, at least in
terms of public health impact. Studies of prenatal exposure
from atomic bomb blasts did not show increased
risk, nor did studies of children of atomic bomb survivors
who were not exposed prenatally [160]. However,
those exposed prenatally may have higher risks as
adults [159, 161].
Concern about leukemia risk from ionizing radiation
also arose in the early 1980s from an apparent cluster
among children living in close proximity to the
Sellafield nuclear fuels reprocessing plant in Seascale,
England. Initial studies suggested that residential proximity
to the plant, and paternal employment at the plant
were risk factors [30–32]. Further studies, however, did
not confirm either risk factor [10, 50, 70, 86, 149]. Kinlen
suggested that this situation supports his population
mixing theory [58].
Another suggested physical environmental cause of
leukemia is radionuclides in water and air. For example,
ingestion of radium-containing groundwater in an ecologic
study conducted in Florida showed an association
with leukemia [80]. Subsequent studies seeking to clarify
this issue provided limited support [6, 17, 29]. Studies
examining inhaled radon found an increased risk of
leukemia, through the hypothesized mechanism of irradiation
to the bone marrow. This association was shown
in ecologic studies but not other studies, and thus is unlikely
to be etiologic [71].
5.3.2.2 Nonionizing Radiation
Concern also has been raised over the apparent elevated
leukemia incidence among children and workers exposed
to electric and magnetic fields (EMF) [49, 98,
100]. The risk was first documented in a case-control
study of children who had lived in homes with high
magnetic fields [156], and the results were replicated
in many subsequent population-based studies [22, 79,
131]. Some studies did not show this association [28,
76, 148]. As yet, no mechanism for this risk has been established.
Prompted by positive results in these studies,