|
DEVELOPING
RESEARCH PROGRAMS
Gene-Environment
Studies of Asthma
among African Americans
SPECIFIC
AIMS
The
overall aim of this
research program is
to set up at the National
Human Genome Center
at Howard University
an infrastructure
for gene-environment
studies of asthma
among African Americans
and other populations
of African descent.
Our initial specific
aims are:
1.
To establish an
animal facility
for asthma studies
2. To continue the
collection of data
on African Americans
and their families
3. To establish
formal collaborations
with academic medical
institutions in
West Africa, and
to develop and test
a mechanism for
collecting pilot
data from homogeneous
populations from
which the ancestors
of African Americans
were drawn.
BACKGROUND
The
incidence of asthma
in African Americans
is four to six times
that among Caucasians,
and it is of considerable
public health concern.
We recognize that
despite steadily improving
health status for
the nation, residents
of our cities still
have a disproportionate
burden of acute and
chronic respiratory
diseases. The contribution
of environmental exposures
to this disease burden
is a critical factor
that needs to be understood
to improve public
health.
Today a majority of
people live in the
cities and by 2050
over 75% of the world's
population will be
urban dwellers. The
inner city poses particularly
unique problems with
the imposition of
multiple environmental
stress factors on
special populations
that may have limited
access to health care.
Thus the public health
challenge that is
facing us is how can
we improve the health
of individuals who
now and the future
will live in urban
environments. Thus
one of our specific
aims is to identify
environmental exposures
that alone increase
risk of illness for
people living in urban
environments, such
as Washington DC,
and to use these findings
to develop prevention
strategies to improve
public health. Dr.
Sampson Sarpong is
using an animal model
at The Johns Hopkins
Asthma Center to study
environmental exposures
to asthma, in particular,
the cockroach allergen.
Establishing an animal
facility at Howard
University will eliminate
the traveling to Baltimore
4 days each week,
saving valuable energy
and time for the program
at Howard University.
Moreover,
recent scientific
findings have strongly
implicated genetic
factors in the etiology
of asthma. Identifying
asthma-specific genes,
polymorphic markers
and candidate gene
loci in African Americans
can be the foundation
of developing more
specific ways of diagnosing
asthma. Early specific
diagnosis can pave
the way to exploring
reliable methods of
prevention of asthma.
Prenatal diagnosis
that can be made possible
by these novel approaches
may conceivably lead
to therapeutic intervention
in utero. Identifying
the candidate loci
of cytokines and the
cytokine messengers
associated with the
expression of asthma
may possibly lead
to the development
of cytokine-specific
antagonists which
can block the clinical
expression of asthma.
Howard
University College
of Medicine participated
in a multi-institutional
and multi-discipline
genome-wide search
for asthma associated
genes in African Americans,
Caucasians and Hispanics.
Our contribution focused
on African Americans
asthma families. Asthma
associated linkage
was established in
chromosome regions
5p15 and 17p11.1-q11.1.
IgE-specific immune
response was found
susceptible to the
genes of the chromosomes
5q31-q33.
Furthermore,
Howard University
is the coordinating
center for a large
genetic study of non-insulin-dependent
diabetes mellitus
in five West African
medical centers -
the AADM project.
Biologically homogeneous
groups from which
the ancestors of African
Americans were drawn
have been identified
for the AADM study.
Protocols for sample
collection and shipment
have been established
and tested, human
subject concerns have
been settled and considerable
data have already
accrued. It is, therefore,
natural to extend
studies to other common
diseases, such as
asthma, which we propose
to begin doing.
Genetic
Epidemiology of Breast
Cancer Among African
American Women
SPECIFIC
AIMS
The
overall aim is to
bring together interested
researchers at Howard
University to develop
an integrated research
program in the genetic
epidemiology of breast
cancer among African
American women. The
specific aims are
the following:
1.
To characterize
the black/white
cross-over in the
age-specific incidence
rates in the United
States, and to determine
the role of genetics
in the racial difference
in the incidence
and survival rates
of breast cancer;
2. To assess the
role of reproductive
and socio-economic
variables in the
etiology and survival
of breast cancer
among African-Americans.
BACKGROUND
The
ethnic patterns of
breast cancer in the
United States are
characteristically
peculiar. African-American
women have historically
an overall lower risk
of developing breast
cancer than white
women. However, this
difference appears
to have narrowed.
The age-adjusted incidence
rates per 100,000
was 87.6 in black
women compared with
108.2 in white women
in 1989, as opposed
to 50.3 and 76.4 in
blacks and whites
respectively in 1947-1949;
SEER data. Since 1969,
a black/white cross-over
in age-specific breast
cancer rate has been
observed: among women
under 40, the incidence
has become higher
among black compared
with white women,
while among women
over 40, the incidence
has remained higher
among white women.
We seek scientific
explanations for these.
If
for breast cancer
the genetic background
is the same for the
two races, except
for a possible difference
in gene frequency,
then why the particularly
high age-specific
incidences rates among
young black women?
Socio-Economic Status
(SES) is believed
to play a role. The
observation is that
in the years preceding
the war and immediately
following it when
poverty was rampant
in Europe, breast
cancer rates were
low, but as the economies
improved after the
war breast cancer
rates rose.
These trends have
been observed in the
United States as well.
And why will SES have
any bearing on a disease
so biologically determined?
The theory is that
high energy protein
intake early in life
leads to earlier maturation
of body organs, in
particular those concerning
reproduction and related
hormones. Thus early
menarche following
from the ripening
of the ovaries becomes
observed risk factor.
Similarly delayed
age at first full
term pregnancy which
is less common among
the socio-economically
disadvantaged, also
becomes a risk factor,
and so on. A more
detailed discussion
of these theories
can be found in Pike
and Spicer (1994),
Pike et al. (1981),
Kelsey et al. (1993),
Russo
et al. (1984, 1990,
1994), Rosner et al.
(1994), and references
cited in those papers.
In seeking a connection
with the peculiar
age-specific incidence
of breast cancer among
black women, our thinking
is that the young
blacks have a better
lot socio-economically
than their forebears.
Unlike
the incidence rates,
the survival of breast
cancer is consistently
poor for black women
compared to white
women. Is this solely
a matter of late detection,
or is there a genetic
basis?
Data
at Howard University
The
following data that
have already accrued
at Howard University:
-
Epidemiology
and Clinical Data
collected on 257
main subjects.
-
Epidemiology
data collected
on 841 family
members of the
main subjects.
-
From
the original Gene
and Environment
Study, 57 families
have so for been
identified/as
having high risk
for genetic susceptibility
to breast cancer.
To be considered
as high risk,
a patient must
meet any one of
the following
conditions: (a)
Has 2 or more
family members
affected with
breast cancer;
(b) be a male
or (c) the age
of onset is 40
years or younger.
-
Microbiology
data have been
collected from
these 57 families.
|
