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Research Projects

 

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.

 
   
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