Centers for Disease Control and Prevention
Centers for Disease Control and Prevention		 Centers for Disease Control and Prevention CDC Home Search CDC CDC Health Topics A-Z    
Office of Genomics and Disease Prevention  
Office of Genomics and Disease Prevention

 

 Journal Publication 

This article was published  in Genet Med 2001 November/December;3(6):405-410

Public Health Impact of Genetic Tests 
at the End of the 20th Century
 Print version

by Paula W. Yoon, 

From the 1 Office of Genomics and Disease Prevention, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia; 2 Division of Laboratory Systems, Public Health Practice Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia; 3 University of Washington School of Medicine, Seattle, Washington.

Purpose: To evaluate genetics tests available for clinical, research, and public health purposes in terms of their public health impact as measured by the number of people who could potentially be tested.

Methods: Genetic tests for the 751 inherited diseases or conditions listed in the GeneTests database as of November 2000, were classified on the basis of their use for population-based testing and the prevalence of the disease or condition being tested. The GeneTests database divides the tests into two groups: those offered for clinical use and those available for research only.

Results: Of the 423 clinical tests, 51 had potentially greater impact on public health because of their use in statewide newborn screening programs, other population screening programs, or testing for common diseases with a prevalence over 1 in 2,000 people. Among the 328 tests performed for research purposes only, 18 met the criteria for potentially greater public health impact.

Conclusions: Our classification scheme indicated that fewer than 10% of the genetic tests listed in the GeneTests database at the end of 2000 are highly relevant to public health. The majority of genetic tests are used in diagnosis and/or genetic counseling for rare, single-gene disorders in a limited number of people. However, as more tests are being considered for newborn screening, and associations between genes and common diseases are being discovered, the impact of genetic testing on public health is likely to increase.

Key Words: genes; genetic tests; public health

PURPOSE

With the Human Genome Project near completion, it is estimated that there are approximately 35,000 human genes.1 More than 9,300 of these genes have been discovered, and for many, the gene locus, allelic variants, function, and some disease associations have been described.2 The discovery of new genes and the rapid commercialization of genetic technology will lead to the development of an increasing number of tests that detect genetic variation. Genetic tests for more than 400 diseases and conditions are currently available in clinical practice and many more are being developed in research settings.3

Despite claims that genomic medicine will revolutionize clinical practice,4 some health professionals have argued that the discovery of genes and their association with disease will have limited application to clinical medicine and public health.5,6 The basis of this argument is that common complex diseases such as cancers and cardiovascular disease result from interactions between many low-penetrant genes and environmental factors that limit the ability to test individuals for genetic susceptibility and to tailor interventions. However, tests that detect genetic variants, such as those that predispose to familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, when used appropriately, can reduce morbidity and mortality.7,8 Furthermore, as our understanding of gene-gene and gene-environment interactions increases, genetics will become an integral part of most, if not all, areas of medicine.

The increasing use of genetic tests necessitates establishing criteria for evaluating the benefits and risks of genetic tests and for assessing the effectiveness of each test in promoting health and preventing disease. In 1998, the Secretary’s Advisory Committee on Genetic Testing (SACGT) was formed to address the medical, ethical, legal, and social issues raised by the development and use of genetic tests and to make recommendations for enhancing the oversight of genetic tests. The SACGT recommended that all new genetic tests that have moved beyond the basic research phase be reviewed to assess their benefits and risks and that the level of review be appropriate for different categories of genetic tests. To ensure that a genetic test receives the appropriate level of review, a classification scheme was proposed to divide tests into two scrutiny levels using three criteria: the analytic validity, use for population screening, and the prevalence of the disease to be tested.9

The purpose of our study was to evaluate the potential public health impact of genetic tests available for clinical, research, and public health purposes. We developed a classification scheme similar to the SACGT scheme and grouped tests according to whether the test is used for population screening and the prevalence of the disease or condition being tested. We also wanted to determine whether these two criteria were sufficient for identifying tests likely to have significant public health impact or whether additional criteria should be considered. Establishing the extent of the use of genetic tests for clinical and public health purposes now before they become more common will provide a baseline for monitoring the impact of genetic tests in the future.


METHODS

We obtained the list of genetic tests used for this study from GeneTests (www.genetests.org).3 GeneTests (formerly called Helix) is a Web-accessible database that lists laboratories that offer genetic testing, both within the United States and elsewhere.10 Laboratory participation in GeneTests is voluntary. GeneTests defines a genetic test as the “analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites to detect alterations related to a heritable disorder. This determination can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers coinherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing).”3 The GeneTests database includes inherited diseases or conditions ranging from diseases due to highly penetrant genes like Huntington disease to diseases where the pattern of inheritance is not as clear but there are known genetic susceptibilities, as with schizophrenia, for example. The database is organized by disease or condition and includes information on the gene(s) associated with the condition (if known), the laboratories that offer the testing, the type of test performed, and whether the test is offered for use in clinical practice or for research purposes only. At the time we prepared a database for our analysis (November 2000), 751 diseases were listed in the GeneTests database.

In addition to the information about associated gene(s) and test purpose (research or clinical), we compiled information about the prevalence of the diseases, if known, and the mode of inheritance (e.g., autosomal recessive, autosomal dominant, X-linked). Information about the mode of inheritance and disease prevalence were obtained from On-Line Mendelian Inheritance in Man (OMIM)2 and various sources, including published studies, text books, on-line pediatric databases, and GeneClinics (www.geneclinics.org).11 We also noted the intended use or settings for the tests (diagnosis, carrier screening, newborn screening, and prenatal diagnosis) and unique considerations that could affect the assessment of public health impact such as disease severity, mortality, age of onset, treatment availability, and special social concerns.

We then used two criteria to group the diseases and conditions into those for which genetic testing would have more public health impact (based on the number of people who could potentially be tested) and those for which it would have less. The first criterion was whether the test is used for population-based screening. Population-based screening is defined as testing individuals who belong to a population-defined subgroup (e.g., age, race/ethnicity) and who have no clinical signs of disease. This type of testing includes newborn screening for diseases such as phenylketonuria (PKU) and population-based carrier screening for diseases such as cystic fibrosis. Predictive testing of people who are presymptomatic but are known to be at risk because of family history, as with Huntington disease, is not considered population-based testing. The second criterion was whether the disease is common or rare. Different cut-off levels have been suggested for defining what is rare and common (SACGT used a prevalence of <1/2,000 or an incidence of <1/10,000 to define rare in its classification scheme).9 We used a prevalence of <1/2,000 to define the rare diseases or conditions. Because we were interested in the number of people who could potentially be tested, we considered the prevalence for the disease as a whole, not just the proportion that is familial. For example, we considered the prevalence of breast cancer, not just hereditary breast cancer. Although practice guidelines specify criteria for testing based on family history and other factors, these guidelines are not always followed carefully and potential exists for more widespread testing.

When a genetic test was used for different purposes, for example, the same test was used for diagnosing disease in a person with clinical symptoms and for population-based carrier testing, the disease was classified at the higher level of potential public health impact. We also compiled a separate list of the tests that were currently listed as research, but could potentially transition into clinical use soon and would affect public health.



RESULTS

Of the 751 tests we evaluated, 423 (56%) were identified by GeneTests as being offered for use in clinical practice and 328 (44%) were identified as being available for research purposes only. Among the 423 clinical tests, we classified 51 as having more public health impact (defined by the number of people who could potentially be tested). This finding represents 12% of tests available for clinical use. The tests classified as having potentially more public health impact are divided into three groups: those used for newborn screening (19 tests), those used for other population screening (9 tests), and genetic tests for common diseases (23 tests) (Table 1, Table 2 and Table 3)

Table 4 lists the 18 diseases for which genetic testing is currently being performed for research purposes only (as of November 2000), but tests for these diseases would meet the criteria for potentially more public health impact if used in clinical practice. If all of the tests were considered regardless of their use for clinical or research purposes, 10% of the tests in the GeneTest database would be classified as having potentially greater public health impact.

DISCUSSION

At the end of the 20th century, most of the genetic tests offered for use in clinical practice are for rare single-gene disorders in people who present with clinical symptoms or who have family histories of genetic diseases. A much smaller proportion of genetic tests (6%) are used for population-based screening, such as state newborn screening programs and carrier testing targeted at ethnic groups at high risk for selected diseases. A similarly small proportion of genetic tests (5%) are being used for common complex diseases such as cancer and cardiovascular conditions. A look at the diseases for which genetic tests are being developed in research settings reveals, however, that tests for additional common conditions are likely to become more prevalent.

Our study was limited in that we considered only genetic tests that are included in the GeneTests database. Although the GeneTests database is believed to be fairly complete for tests being used in clinical practice, the listing of genetic tests used for research purposes is incomplete. We limited our assessment of the impact of genetic tests on public health to criteria that were fairly objective and easy to measure: disease prevalence and use of the test for population screening. Additional criteria could be considered, including disease severity, mortality, age of onset, treatment availability, efficacy, cost of diagnosis and treatment, accuracy of the test, and numerous ethical, and legal and social issues. These important criteria should be considered when new tests are being developed and approved for clinical use.

We based our assessment of public health impact primarily on the number of people who could potentially be tested, and the majority of tests we evaluated were easy to classify. However, our evaluation of genetic tests for a few diseases raised some important issues. Some of the diseases we reviewed have complex gene-disease relations, and our assessment did not account for the clinical validity of the tests or testing process. Clinical validity measures how accurately the test identifies or predicts the disease or clinical condition. Identifying a genetic mutation is not sufficient to diagnose or predict disease. The expression or penetrance of gene mutations varies. Although many of the genetic tests we evaluated were for highly penetrant gene mutations that lead to unique clinical syndromes, in a few diseases such as hemochromatosis and hereditary breast cancer, no consensus exists about clinical validity in many settings.

Another important consideration is the intended use or setting for a genetic test. Some of the tests we evaluated were used for different purposes. For example, genetic testing for Bloom syndrome in symptomatic people would be considered as having less public health impact than carrier testing for this condition among people of Jewish heritage. Similarly, testing for medium chain acyl-coenzyme A dehydrogenase deficiency (MCAD) would have more public health impact when used for newborn screening than it would when used for diagnosing clinical symptoms. Another aspect of intended use is the specific gene being tested. We found instances where one genetic test could be used for multiple conditions. For example, hyperlipidemia type III is rare, but testing is based on ApoE genotyping as is testing for late-onset familial Alzheimer disease.

Determining whether a disease was rare or common was difficult for many of the diseases we evaluated. Prevalence and incidence data are limited for the majority of diseases and conditions for which genetic testing is being offered today. In many instances, we had to infer that a disease was rare on the basis of the few cases reported in the literature. Although we used a cut-off level of <1/2,000 to define a rare disease, we could have used the same definition of a rare disease as both the National Institutes of Health, Office of Rare Diseases,12 and the National Organization of Rare Diseases.13 They define rare as a disease that affects fewer than 200,000 people in the United States. That translates to a prevalence of approximately 1/1,350 people, given the current U.S. population. Using this lower cut-off level to define rare diseases would not have changed the results of this study.

Although the majority of rare diseases we evaluated did not have substantial public health impact by our criteria, some rare conditions are associated with unique medical, ethical, legal, and social issues. Examples include acute intermittent porphyria, which has a higher prevalence in psychiatric populations; and Huntington disease, where the test is predictive, the condition is uniformly fatal, and no treatment is available. These diseases affect a very small percentage of the population, but potential risks (including social, economic, psychological, and medical harms) associated with genetic testing warrant careful monitoring.

Pharmacogenomic tests also warrant consideration. These tests determine individual response to pharmacologic agents. Few pharmacogenomic tests are used in clinical practice today, but many are being developed.14 Although the adverse drug reactions that are being tested for are rare, the important public health issue is how many people have the disease or condition being treated and could potentially be tested. Pharmacogenomic testing is being developed to treat common conditions such asthma15 and to identify people at risk due to common exposures such oral contraceptives.16 These genetic tests have the potential to affect many people.

In summary, our assessment of genetic tests offered at the end of 2000 showed that only a small percentage of genetic tests are highly relevant to public health. The majority of genetic tests are used in diagnosis and/or genetic counseling for rare, single-gene disorders in a limited number of people. Although individually inherited disorders are rare, in aggregate, they represent approximately 5% of the total disease burden in the population.17 As more genetic tests are considered for newborn screening, and associations between genes, the environment, and common diseases are discovered, the number of people who could potentially be tested will certainly increase. The two-criteria classification scheme used in our study represents a basic and simple model for test assessment. To develop a paradigm for review and approval of new genetic tests for clinical and public health applications, critical issues such as clinical validity and utility, intended use, factors affecting disease prevalence, and genetic variations influencing individual response to medicines or environmental exposure need to be considered. In response to these and other issues, the Centers for Disease Control and Prevention has initiated activities to make information about genetic tests more available to medical professionals and the public, establish standard methods for collecting data to evaluate genetic tests, and monitor the impact of genetic testing on individuals, families, and society.18


Acknowledgements

The authors thank Dr. Roberta Pagon, Medical Director of GeneTests, for her thoughtful comments on the manuscript.


References

  1. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860–921.  
  2. Online Mendelian Inheritance in Man, OMIM (TM). McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD), and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 2000 http://www3.ncbi.nlm.nih.gov/OMIM/. 
  3. GeneTests, 2001. http://www.genetests.org/. 
  4. Collins FS, McKusick VA. Implications of the Human Genome Project for medical science. JAMA 2001; 285: 540–544.  
  5. Holtzman NA, Marteau TM. Will genetics revolutionize medicine? N Engl J Med 2000; 343: 141–144.   
  6. Vineis P, Schulte P, McMichael AJ. Misconceptions about the use of genetic tests in populations. Lancet 2001; 357: 709–712. 
  7. Rabelo R, Foulkes W, Gordon PH, Wong N, Yuan ZQ, MacNamara E, Chong G, Pinsky L, Lasko D. Role of molecular diagnostic testing in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer families. Dis Colon Rectum 2001; 44: 437–446.
  8. Renonene-Sinisalo L, Aarnio M, Mecklin JP, Jarvinene HJ. Surveillance improves survival of colorectal cancer in patients with hereditary nonpolyposis colorectal cancer. Cancer Detect Prev 2000; 24: 137–142.
  9. Department of Health, and Human Services, Secretary’s Advisory Committee on Genetic Testing. Request for public comment on a proposed classification methodology for determining level of review for genetic tests. Federal Register 2000; 65: 76643–76645.
  10. Tarczy-Hornoch P, Covington ML, Edwards J, Shannon P, Fuller S, Pagon RA. Creation and maintenance of helix, a Web based database of medical genetics laboratories, to serve the needs of the genetics community. Proc AMIA Symp 1998; :341–345. 
  11. GeneClinics, 2001. http://www.geneclinics.org/index.html.
  12. National Institutes of Health, Office of Rare Diseases, 2001. http://rarediseases.info.nih.gov/ord/diseases.html. 
  13. National Organization of Rare Diseases, 2001. http://www.rarediseases.org/. 
  14. Mancinelli L, Cronin M, Sadee W. Pharmacogenomics. The promise of personalized medicine. AAPS Pharmsci 2000; 2(1) article 4. 
  15. Liggett SB. The pharmacogenetics of ß2-adrenergic receptors: Relevance to asthma. J Allergy Clin Immunol 2000; 105: S487–S492.  
  16. Vandenbroucke JP, van der Meer FJJM, Helmerhorst FM, Rosendaal FR. Factor V Leiden. Should we screen oral contraceptive users and pregnant women? BMJ 1996; 313: 1127–1130. 
  17. Rimoin DL, Connor JM, Pyeritz RE, editors. Principles and practices of medical genetics, 3rd ed. London: Churchill Livingstone, 1997: 31.  
  18. Office of Genomics and Disease Prevention, Centers for Disease Control and Prevention, 2001. http://www.cdc.gov/genetics/default.htm.

Received: July 16, 2001.

Accepted: September 6, 2001.

Paula W. Yoon, ScD, MPH, Office of Genomics and Disease Prevention, CDC/NCEH, MS K-89, 4770 Buford Highway, Atlanta, GA 30341-3724.

Genet Med 2001 November/December;3(6):405-410
Copyright © 2001 American College of Medical Genetics. All rights reserved
 Published by Lippincott Williams & Wilkins