Using ZIP Code and GIS Studies to Assess Disease Risk
Environ Health Perspect. doi:10.1289/ehp.10840 available via http://dx.doi.org [Online 19 December 2007]
In several recent articles in EHP,
investigators have attempted to link proximity to hazardous waste
sites, as
measured by geographic information systems (GIS) or ZIP codes,
with increased incidences of various diseases. An implicit
assumption in these studies is that proximity is a surrogate
for exposure. However, numerous studies have demonstrated that
the presence of chemicals in an individual's environment
does not necessarily translate into a dose. For example,
Stehr-Green et al. (1988) found that
Serum PCB [polychlorinated
biphenyl] levels in persons at highest risk of nonoccupationally
related
exposures … at 10 sites were within background ranges,
even though environmental contamination levels as high as 2.5
parts
per billion (ppb) in monitoring well water samples and 330,000
ppb in soil samples were measured.
In a recent study, Fitzgerald et al.
(2007) investigated the impact of living near a known source
of PCBs on the body burdens of local residents and concluded
that
The results indicate no detectable
differences in serum PCB levels according to proximity or wind
direction relative to local point sources.
Table 1.
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Consequently, it is erroneous to conclude
that simply living in geographic proximity to a potential
source is synonymous with an exposure, much less a dose, which
is the critical determinant of risk.
The pitfalls of relying
on spatial location as a surrogate for exposure and potential
disease risk
is illustrated by the study of Kouznetsova et al. (2007), which
using ZIP codes reported an increased rate of hospitalization
for diabetes and residential proximity to PCBs as a consequence
of living near the Hudson River. The authors described this
study as hypothesis generating, but nevertheless concluded that
it provided "additional support for a relationship
between exposure to environmental contaminants, especially
POPs, and risk of diabetes." We do not understand how a
hypothesis-generating study (with no ability to account for a
single known risk factor for diabetes) would offer support for
an association between a chemical and a disease.
The hypothesis that PCB exposure might be
etiologically involved in diabetes risk is not supported by the
numerous mortality studies of PCB-exposed workers, none of
which were mentioned by Kouznetsova et al. (2007). Table 1
summarizes diabetes mortality in all PCB-exposed occupational
cohorts in which such data were reported. These data show no
evidence that even prolonged occupational exposure to PCBs,
with resulting accumulations approximately 100 times greater
than background exposure, poses an increased risk of diabetes.
It is reasonable to presume that if PCBs were etiologically
implicated as a risk factor for diabetes, there would be
increased mortality from diabetes in these cohorts. Because
there is not, a more biologically plausible explanation for the
findings of increased incidence of diabetes associated with
environmental exposure to PCBs is that the accumulation and/or
excretion of PCBs is a consequence of diabetes-related
metabolic perturbations, not that diabetes is caused by PCBs.
The authors consult for the General
Electric Company on matters pertaining to PCBs.
References
Fitzgerald EF, Belanger
EE, Gomez MI, Hwang SA, Jansing RL, Hicks HE. 2007. Environmental
exposures
to polychlorinated biphenyls (PCBs) among older residents of
upper Hudson River communities. Environ Res 104(3):
352–360.
Kimbrough RD, Doemland
ML, Mandell JS. 2003. A mortality update of male and female capacitor
workers
exposed to polychlorinated biphenyls. J Occup Environ Med 45(3):
271–282.
Kouznetsova M, Huang X,
Ma J, Lessner L, Carpenter DO. 2007. Increased rate of hospitalization
for
diabetes and residential proximity of hazardous waste sites.
Environ Health Perspect 115:75–79.
Loomis D, Browning SR,
Schenck AP, Gregory E, Savitz DA. 1997. Cancer mortality among
electric utility
workers exposed to polychlorinated biphenyls. Occup Environ Med
54:720–728.
Prince MM, Hein MJ, Ruder AM, Waters MA,
Laber PA, Whelan EA. 2006a. Update: cohort mortality study of
workers highly exposed to polychlorinated biphenyls (PCBs)
during the manufacture of electrical capacitors, 1940-1998.
Environ Health 5:13; doi:10.1186/1476-069X-5-13 [Online 22 May
2006].
Prince MM, Ruder AM, Hein
MJ, Waters MA, Whelan EA, Nilsen N, et al. 2006b. Mortality and
exposure
response among 14,458 electrical capacitor manufacturing
workers exposed to polychlorinated biphenyls (PCBs). Environ
Health Perspect 114:1508–1514.
Ruder AM, Hein MJ, Nilsen
N, Waters MA, Laber P, Davis-King K, et al. 2006. Mortality among
workers
exposed to polychlorinated biphenyls (PCBs) in an electrical
capacitor manufacturing plant in Indiana: an update. Environ
Health Perspect 114:18–23.
Stehr-Green PA, Welty E,
Burse VW. 1988. Human exposure to polychlorinated biphenyls at
toxic waste
sites: investigations in the United States. Arch Environ Health
43(6):420–424.
ZIP Code and GIS Studies: Kouznetsova et al. Respond
Environ Health Perspect. doi:10.1289/ehp.10840R available via http://dx.doi.org [Online 19 December 2007]
There is strong evidence
that exposure to persistent organic pollutants (POPs), including
polychlorinated
biphenyls (PCBs), is associated with an increased risk of
diabetes, and that evidence does not come only from studies of
residential proximity to waste sites. In our studies in an
adult Native-American population, individuals in the top
tertile of serum PCBs showed a 3.9-fold [95% confidence
interval (CI), 1.5–10.6] elevated risk of diabetes after
adjustment for age, body mass index, smoking, sex, and serum
lipid levels (Codru et al. 2007). Diabetes was defined as
either taking prescription antidiabetes medication or having a
fasting glucose level of > 125 mg/dL. In another study, Lee
et al. (2006), using NHANES (National Health and Nutrition
Examination Survey) data, found a dose-dependent relationship
between prevalence of diabetes and serum concentrations of six
different organochlorine compounds, including one PCB. Other
studies reporting this relationship are cited in our recent
article (Codru et al. 2007).
The occupational studies listed by Golden
and Schell do not demonstrate a relationship with diabetes.
However, absence of evidence does not mean evidence of absence.
Most occupational studies have poor exposure assessment and
short follow-up periods, and are compromised by the
healthy-worker effect.
Studies such as ours (Kouznetsova et al.
2007) do, of course, have limitations, in that we do not have
personal information of exposure to individuals beyond their
ZIP code of residence. But they also have strengths, especially
in the very large numbers of hospitalizations and the
uniformity of the data-collection system in New York. We
recognize the limitations, which we discussed extensively in
our article. Although it is difficult to control for all
confounders in investigations such as this, they are hypothesis
generating and should lead to studies where exposure can be
better assessed. This we have done. Our parallel study (Codru
et al. 2007), in which we assessed exposure by measuring serum
PCBs and fasting glucose, provided extremely strong support
for
the conclusion of Kouznetsova et al. (2007): that simply living
near a PCB-contaminated site (in this case the Hudson River)
poses a risk of both exposure and disease.
We have also reported an elevated rate of
hospitalization for cardiovascular disease and heart attacks
among individuals living in ZIP codes containing waste sites
contaminated with POPs, especially along the Hudson River
(Sergeev and Carpenter 2005). Also, in another study with
excellent exposure assessment, we demonstrated that elevated
exposure to PCBs leads to elevated levels of serum lipids
and
heart disease in a human population (Goncharov et al. 2007).
Golden and Schell actually
have two arguments, each fallacious. First, they discount our
evidence
that residential proximity to hazardous waste sites leads to
disease, arguing that some others have not demonstrated
elevated serum PCB levels. The above observations show that
this is not so. Golden and Schell's last sentence
basically accepts the evidence that "increased incidence
of diabetes [is] associated with environmental exposure to
PCBs," but then they argue that this relationship is a
consequence of diabetes-related metabolic perturbations. You
really cannot have it both ways. We have demonstrated that
residence near the Hudson River (where average income is higher
and there is less smoking, more exercise, and better diet than
in the rest of New York State) is associated with increased
rates of hospitalization for not only diabetes and heart
disease but also hypertension (Huang et al. 2006), stroke
(Shcherbatykh et al. 2005), and chronic respiratory disease
(Kudyakov et al. 2004). These associations cannot be explained
away by "diabetes-related metabolic
perturbations."
The mechanisms responsible for the
relationship between PCB exposure and these multiple chronic
diseases are not certain, but it is likely that they result
from secondary to posttranscriptional gene regulation. The
studies of Adeeko et al. (2002) and Vezina et al. (2004)
demonstrate that a very large number of diverse genes show
altered expression upon exposure to POPs. There is still a lot
that we do not know, but it is very clear that these chemicals
are dangerous compounds and that exposure to them is associated
with an elevated risk of a variety of chronic human diseases.
The authors declare they have no competing
financial interests.
Maria Kouznetsova
Xiaoyu Huang
Jing Ma
Lawrence Lessner
David O. Carpenter
Institute for Health and the Environment
University at Albany, SUNY
Rensselaer, New York
E-mail: carpent@uamail.albany.edu
References
Adeeko A, Li D, Doucet
J, Cooke GM, Trasler JM, Robaire B, et al. 2002. Gestational
exposure to
persistent organic pollutants: maternal liver residues,
pregnancy outcome, and effects on hepatic gene expression
profiles in the dam and fetus. Toxicol Sci 72:242–252.
Codru N, Schymura MJ, Negoita
S, Akwesasne Task Force on the Environment, Rej R, Carpenter
DO. 2007.
Diabetes in relation to serum levels of polychlorinated
biphenyls and chlorinated pesticides in adult Native Americans.
Environ Health Perspect 115:1442–1447.
Goncharov A, Haase RF, Santiago-Rivera A,
Morse G, Akwesasne Task Force on the Environment, McCaffrey RJ,
et al. 2007. High serum PCBs are associated with elevation
of
serum lipids and cardiovascular diseases in a Native American
population. Environ Res doi:10.1016/j.envres.2007.10.006
[Online 4 December 2007].
Huang X, Lessner L, Carpenter
DO. 2006. Exposure to persistent organic pollutants and hypertensive
disease. Environ Res 102:101–106.
Kouznetsova M, Huang X,
Ma J, Lessner L, Carpenter DO. 2007. Increased rate of hospitalization
for
diabetes and residential proximity of hazardous waste sites.
Environ Health Perspect 115:75–79.
Kudyakov R, Baibergenova
A, Zdeb M, Carpenter DO. 2004. Respiratory disease in relation
to patient
residence near to hazardous waste sites. Environ Toxicol
Pharmacol 18:249–257.
Lee DH, Lee IK, Song K,
Steffes M, Toscano W, Baker BA, et al. 2006. A strong dose-response
relation
between serum concentrations of persistent organic pollutants
and diabetes. Diabetes Care 29:1638–1644.
Sergeev A, Carpenter DO.
2005. Hospitalization rates for coronary heart disease in relation
to residence near areas contaminated with persistent organic
pollutants and other pollutants. Environ Health Perspect 113:
756–761.
Shcherbatykh I, Huang X, Lessner L,
Carpenter DO. 2005. Hazardous waste sites and stroke in New
York State. Environ Health 4:18; doi:10.1186/1476-069X-4-18
[Online 29 August 2005].
Vezina CM, Walker NJ, Olson
JR. 2004. Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153:
effect
on hepatic gene expression. Environ Health Perspect 112:
1636–1644. |
