This issue of the Journal contains the first two published Human
Genome Epidemiologic (HuGE) reviews, which
are systematic, structured, peer-reviewed
synopses of epidemiologic aspects of human
genes in relation to specific diseases. In
the first review, Cotton et al. (1) evaluate
the relations between glutathione S-transferase
polymorphisms and colorectal cancer. In the
second review, Rasmussen and Friedman (2)
assess epidemiologic aspects of the neurofibromatosis
1 (NF1) gene and its relation to the
relatively common Mendelian condition. As
such, these reviews represent the spectrum
of
the relations between genes and diseases (from
single gene disorders to multifactorial conditions).
Both HuGE reviews illustrate the range of
methodological problems likely to occur when
reviewing data from investigations of the
relations between other genes and other diseases.
Even for the single gene disorder, neurofibromatosis
type 1, there is wide variation in the clinical
phenotype, even in individuals with the same
NF1 gene mutation. It seems that many
of the other factors involved in determining
clinical manifestations have not yet been
determined. In addition, although a protein
truncation test for NF1 mutations is
commercially available, its sensitivity, specificity,
and predictive value have not been established.
With regard to glutathione S-transferase
polymorphisms and colorectal cancer, many
of the published studies have been subject
to selection and participation bias, and some
have had limited statistical power, particularly
for subgroup analyses. It is difficult to
assess how much these methodological problems
may account for the inconsistencies in the
results. The limited statistical power of
small studies to detect associations between
genotype and disease is particularly important
with regard to effect modification, and as
yet, few studies have investigated interactions
between glutathione S-transferase genotypes
and environment.
These articles are among 40 or so such reviews
currently in preparation after the announcement
in 1998 of the formation of the Human Genome
Epidemiology Network (HuGENet™) and the partnership
between the American Journal of Epidemiology,
Epidemiologic Reviews, and the Centers
for Disease Control and Prevention in seeking
and publishing such peer-reviewed articles
(3). This partnership reflects the increasing
recognition by the editors of the American Journal of Epidemiologyand Epidemiologic Reviews of the role of genetics in epidemiologic
research.
In brief, HuGENet™ represents a global collaboration
of individuals and organizations from diverse
backgrounds who are committed to the development
and dissemination of population-based human
genome epidemiologic information. The goals
of such an endeavor are 1) to establish an
information exchange network that promotes
global collaboration in the development and
dissemination of peer-reviewed epidemiologic
information on human genes; 2) to develop
an updated and accessible knowledge base on
the World Wide Web; and 3) to promote the
use of this knowledge base by health care
providers, researchers, industry, government,
and the public for making decisions involving
the use of genetic tests and services to improve
health and prevent disease. Additional information
about this "virtual" collaboration
can be found on the HuGENet™ website (4).
The term HuGE denotes an evolving field of
inquiry that uses systematic applications
of epidemiologic methods and approaches in
population-based studies of the impact of
human genetic variation on health and disease
(3). Human genome epidemiology can be viewed
as the intersection of genetic epidemiology
(primarily concerned with finding genes),
molecular epidemiology (primarily concerned
with using genetic markers in epidemiologic
studies of risk), and applied epidemiology
(primarily concerned with health services
research on the impact of genetic tests and
ser-vices). With the impending completion
of the human genome project and the identification
of the 50,000 -100,000 human genes in the
next few years
(5), there will be a "huge" need
for an epidemiologic approach to evaluate
the role of gene variants in the occurrence
of various human diseases (6).
Since the formation of HuGENet™, a wide array
of medical and public health professionals
have voiced concerns about the increasing
gap between gene discovery and the implementation
of disease prevention measures in which information
on genetic variation might be used. The translation
from gene discovery to disease prevention
depends to a large extent on rapidly developing
the scientific information by means of conducting
high-quality, population-based investigations
on gene-disease relations, including study
of gene-environment interactions, integration
of the evidence from these investigations,
and evaluation of disease interventions. This
is the approach that HuGE represents.
HuGENet™ has also witnessed a growing membership
roster, a liaison board, and a recently formed
editorial board (4). It is widening its collaborative
base with several journals, including Genetics
in Medicine, Teratology, and Emerging
Infectious Diseases.
We hope readers will find these reviews pertinent,
timely, and helpful, especially in evaluating
the currently existing gaps of information.
We also hope readers will contribute to the
building of this knowledge base by collaborating
and conducting HuGE reviews of their own. |