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Dr Collins discusses the
implications of gene-based medicine using a hypothetical case scenario
of a 23-year-old college graduate evaluated for elevated cholesterol
levels in the year 2010 (1). Through pertinent use of genetic tests, the
patient learns about his risks for various conditions based on his
genetic profile and about available interventions to modify these risks.
Dr. Collins paints
an optimistic scenario in which the types of data needed will be
available by 2010. However, even as the Human Genome Project nears
completion, there is little investment in studies than can provide the
clinically meaningful risk estimates assumed by Dr. Collins.
Family-based studies tend to overestimate
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the penetrance of genetic
variants as shown in recent studies of BRCA1 and breast/ovarian cancers
(2) and the Apolipoprotein E-E4 allele and Alzheimer’s disease (3).
Given the paucity of population-based data for many newly discovered
human gene variants, appropriate health policy on the use of genetic
tests will not be possible by the year 2010 even if ethical, legal and
psychosocial issues are resolved.
A systematic population-based
clinical-epidemiologic approach to human genome variation was recently
termed human genome epidemiology (HuGE) (4). HuGE uses epidemiologic
methods in population studies to assess the 1) prevalence of gene
variants; 2) magnitude of disease risk associated with gene variants
(relative, absolute and attributable); 3) magnitude of disease risk
associated with gene-gene and gene-environment interactions; 4) clinical
validity and utility of genetic tests; and 5) the determinants and
impact of using genetic tests. Such studies can be done using
traditional epidemiologic designs (e.g. cohort and case-control
studies).
Given the massive amount of genomic data
that will be generated over the next decades, a coordinated global
effort is needed to develop and disseminate human genome epidemiologic
information. For this to be accomplished, there must be collaboration
between epidemiologists and researchers from various specialties. In
1998, a collaboration of individuals from government, academia,
industry, and professional organizations launched the Human Genome
Epidemiology Network (HuGE Net). This effort seeks to develop and
disseminate an epidemiologic knowledge base on human genes on the
Internet and to promote its use for policy making (5). Only after
epidemiologic studies on thousands of genes are completed will we have
the types of data needed to translate such discoveries into a gene-based
vision of medical practice in the 21st century.
References
- Collins FC. Shattuck Lecture-Medical
and societal consequences of the Human Genome Project. New Engl J Med
1999;341:28-37.
- Struewing JP, Hartge P, Wacholder S,
et al. The risk of cancer associated with specific mutations of BRCA1
and BRCA2 among Ashkenazi Jews. N Engl J Med 1997;336:1401-8.
- Tang MX, Stern Y, Marder K, et al. The
APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites,
and Hispanics. JAMA 1998;279:751-5.
- Khoury MJ. Human Genome Epidemiology
(HuGE). Translating advances in human genetics into population-based
data for medicine and public health. Genetics in Medicine 1999;1:71-4.
- Khoury MJ, Dorman JS. The Human Genome
Epidemiology Network. Am J Epidemiol 1998;148:1-3.
Muin J. Khoury M.D., Ph.D.
Office of Genomics and Disease Prevention, Centers for Disease Control
and Prevention
4770 Buford Hwy, MailStop K28, Atlanta, Georgia 30341
Phone 770-488-3235, Fax 770-488-3236, E-Mail: genetics@cdc.gov
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