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Bladder cancer case-control
study in
This study was based in Villa María, Córdoba.
The study is defined by 3 major components for which final data analysis and
report preparation is currently underway:
- Arsenic and bladder
cancer dose-response: Bladder cancer cases and age- and sex-matched
population controls from the
- Metabolism:
First-morning urine samples were collected from cases and controls.
Analyses for inorganic arsenic and its methylated metabolites were
conducted in the laboratory of Professor David Kalman,
Molecular epidemiology: Tumor DNA has been analyzed for genetic
alterations using a three-tiered approach:
- screening of the
entire genome for gains and losses using comparative genomic
hybridization (CGH);
- specific analyses of
chromosomes 9 and 17p for loss of heterozygosity using PCR- based
methods;
- analysis of the p53
gene for mutations, using polymerase chain reaction-single-strand
conformation (PCR-SSCP).
The frequency and
pattern of these genetic alterations in bladder tumors of arsenic-exposed and
unexposed cases is being compared. The potential synergistic action of arsenic
on genotoxic effects of cigarette smoking is currently being assessed. In
addition, susceptibility differences between cases and controls is being
investigated by identifying the presence or absence of the glutathione
S-transferases GSTM1 and GSTT1 null genotypes in buccal cells and by comparing
urinary arsenic methylation patterns.
Mortality from internal cancers was identified
in areas of the
Cross-sectional survey
of arsenic-induced skin lesions in Chiu-Chiu, Northern Chile
In March 1999 a cross-sectional survey
was conducted of families from two small remote villages in Region II of Chile.
One village, Chiu- Chiu, was exposed to drinking water containing 800 ug/L of
arsenic. The second village, Caspana, has low concentrations of arsenic in its
water supply (15 ug/L). A total of 11 families participated from Chiu-Chiu and
8 from Caspana, each consisting of two adults and two children. The families
were examined for skin lesions and nutritional status and the findings are
currently being prepared for publication.
Impact of arsenic on
mortality in
The purpose of this study is to investigate
mortality in Region II of Chile, from 1950 to 2000. This region, currently with
a population of close to a half million people, experienced a peak exposure to
arsenic, with a population-weighted average drinking water arsenic
concentration of 580 ug/L, from 1955 to 1970. In contrast, water supplies
for the rest of
An investigation of mortality in Region II during 1989-1993 indicated that
rates for bladder, skin, lung, and kidney cancer were increased compared to the
rest of
The study underway is constructing a longitudinal mortality profile, by cause
of death for Region II between the years 1950 and 2000. A similar mortality
profile is being constructed for Region V, as an unexposed control region. As
well as cancer, increased mortality might be expected from non-cancer outcomes,
including cardiovascular, peripheral vascular and cerebrovascular diseases. The
impact of arsenic exposure during childhood on pulmonary disease mortality in
young adults, and on childhood cancer mortality, is also being assessed.
This study is taking advantage of a unique opportunity to investigate
arsenic-caused mortality, including latency patterns, for one of the world's
most significant environmental toxic exposures. The study is expected to
be completed in the first half of 2004.
Dose-response study of
arsenic-caused skin lesions in West Bengal,
Our group is conducting research in
collaboration with Professor D. N. Guha Mazumder and his research team at
the
We recently completed data collection for a
case-control study nested in the same survey, which focuses on participants
with skin lesions who had drinking water arsenic levels of less than 500 ug/L.
Detailed interviews concerning water sources and fluid consumption, diet,
smoking and medical history were completed for over 400 participants. Water
samples were obtained from all known drinking water sources. Each participant
received a physical examination for skin lesions and other signs, and portable
spirometry was conducted. Blood and urine samples were also collected to assess
micronutrient status and arsenic metabolism. Data from this study are currently
being analyzed.
Studies on the effect of arsenic on respiratory, reproduction and child development in West Bengal
In addition to the dose-response study, we
recently launched two new studies in
The first new study was generated by our
preliminary findings from a cross-sectional study in which we examined the
respiratory effects associated with ingesting arsenic (see Guha Mazumder et
al., 2001). The prevalence of cough, chest sounds, and shortness of breath were
dramatically elevated among individuals with skin lesions. These findings
raised the possibility that respiratory effects are largely present only in
people with skin lesions. We, therefore, set out to confirm these results in a
more focused study. Participants will include 135 individuals who have
arsenic-induced skin lesions, and were exposed to high arsenic levels (>500
ug/L) through their primary water sources. The comparison group will include
individuals with normal skin, but consumed water with low arsenic levels
(<50 ug/L). Data collection for this detailed study commenced April 2001.
The second investigation examines the potential
effects of arsenic on reproduction and child development. Extensive
studies have been conducted concerning various effects of ingestion of
inorganic arsenic in drinking water, and health effects in adults. So far little
has been done to investigate reproductive effects in pregnancy and effects on
child development. The goal of the proposed study is to investigate pregnancy
outcomes in a retrospective study of 100 women already known to have been
drinking water containing more than 500 ug/L of arsenic. These women will be
compared to 100 women whose drinking water contained less than 50 ug/L of
arsenic. Live births, birth spacing, spontaneous abortion, and stillbirths will
be compared between exposed and unexposed mothers. Children aged 5-15 will
receive a medical examination, and their cognitive abilities and learning
achievements will be evaluated. Detailed nutritional assessment of each family
will be undertaken to search for potential effect modifying role of nutrition
on arsenic effects. Urine samples will be collected from women and their
children to identify metabolic susceptibility. Interviews for this study
commenced April 2001.
Bladder cancer case-control study in
The California/Nevada bladder cancer
study is a population-based, case-control study that will examine the
hypothesis that bladder cancer is caused by ingestion of arsenic in drinking
water at relatively low concentrations. The study population includes residents
of
Increasing evidence suggests that
arsenic in drinking water is an important cause of human cancer, including
bladder cancer. Methylation of inorganic arsenic after ingestion reduces its
toxicity, but little is known about the impact of diet on arsenic methylation,
nor about variation between people in the fraction of inorganic arsenic
methylated in the body. The specific aims of this project are: 1.To assess the
influence of diet on the extent of methylation of inorganic arsenic. 2.To
quantify intra-individual and inter-individual variability in arsenic
methylation. 3.To compare arsenic methylation patterns between bladder cancer
patients and controls. The study population involves a subset of the bladder
cancer cases and frequency matched controls who are being selected as part of
an on-going case-control study on the cancer risks associated with moderate
levels of arsenic in drinking water. Study participants are residents of
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