Acute Leukemias - Republican Scientific Medical Library

82 Chapter 5 · Acute Lymphoblastic Leukemia: Epidemiology and Etiology
smoking and certain parental dietary constituents have
been associated with increased risk of ALL, although
there are no accepted mechanisms of action. Breast
feeding was thought to be protective against ALL [36],
but this effect has not been supported by more recent
data [74].
5.2.8 Socioeconomic Status
The apparent excess observed in several studies of ALL
in whites and other ethnic groups compared to blacks
has led several investigators to suggest that the incidence
of ALL may be directly associated with higher socioeconomic
status (SES). While probably not a direct
cause, SES may be a useful marker for underlying risk
factors that may help us better understand the etiology
of ALL.
One must be specific in what one means by SES. SES
can be inferred from data on individuals (e.g., head of
household or family), or aggregate data (e.g., averages
from census regions, such as tracts, communities, or
zip codes). In addition, there is a wide variety of metrics
used, such as mean income, median income, per capita
income, percent below poverty line. While related, each
can give somewhat different results [63, 106].
In general, studies of SES and childhood ALL have
yielded mixed results. A review of six pre-1983 studies
reported a positive association between SES and childhood
ALL in five of six studies [40]. Studies using residential
neighborhood or community measures of SES
generally found that ALL was more common in areas
of higher SES, although some critics suggested that this
was due to a diagnostic bias, such as in a recent Canadian
study (OR = 0.9, 95% CI 0.8–1.0) [12], possibly attributable
to greater access to good medical care. A recent
Danish study that reviewed this issue reported that
in previous studies individual measures of SES gave inconsistent
results while SES measures of a child’s residential
area tended to be associated with higher leukemia
rates, although some recent studies were less clear
or found the opposite effect [111]. In their own data, they
found that community rather than individual SES was
associated with risk of ALL and, specifically, children
born into poorer regions were at a statistically significant
greater risk (RR = 2.2, 95% CI 1.1–4.6). No association
was found with SES at diagnosis. The most recent
review, by Poole and colleagues, reported that associations
between childhood leukemia and SES varied with
place and time [106]. They also suggest that different
SES measures (e.g., income and education) collected
at different scales (e.g., individual or community) may
be surrogates for different risks and therefore should
be reported separately. SES remains an interesting but
confusing marker for risk of ALL. One complicating factor
noted by Buffler and colleagues is that SES may be
correlated with and even a surrogate for various environmental
exposures, such as pesticides, traffic, and
diet [13]. Since many studies adjust for SES because often
it is believed to be a confounder, these adjustments
may remove any associations between environmental
exposures and ALL, obscuring potential etiologic associations.
5.3 Etiology
It is somewhat surprising how little is known about the
causes of ALL. It occurs more commonly among whites
and in Western, affluent countries, reaches peak incidence
among children, a population of great concern,
and often is reported in concentrated clusters (high local
incidences), a situation that one might think would
be particularly amenable to etiologic study. Among
childhood, only ionizing radiation and certain genetic
disorders are known risk factors. Many other risk factors
have been suggested but remain under investigation,
such as exposure to pesticides, automobile exhaust,
certain chemicals such as benzene, nonionizing
radiation (e.g., magnetic fields), parental exposures
(e.g., cigarette smoking, alcohol consumption and use
of some pharmaceuticals), and even parental consumption
of certain dietary constituents.
5.3.1 Biological Factors
5.3.1.1 Genetics of Childhood ALL
Leukemia, like other forms of cancer, is ultimately a disease
of the DNA. Although single-gene mutations (e.g.,
BRCA1 and BRCA2) are known to predispose to solid tumors
(e.g., carcinomas of breast and ovary), no such
single-gene mutations have been linked to childhood
ALL, which tends instead to be associated with chromosomal
anomalies.