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Human Genome News, May 1994; 6(1)

NIH NACHGR Issues Statement on Use of DNA Testing for Presymptomatic Identification of Cancer Risk

The following statement was adopted by the NIH National Advisory Council for Human Genome Research (NACHGR) at its scheduled January meeting in Washington, D.C., and endorsed by the DOE-NIH Ethical, Legal, and Social Implications Working Group. [Reprinted from JAMA 1994; 271: 785]

Recent advances in the genetics of cancer have raised the possibility of widespread DNA testing for the detection of predisposition to cancer. This may allow individuals at high risk to avail themselves of preventive measures and potentially avoid early death. At least one company has already announced plans to begin offering testing for genetic cancer risk. While much alleviation of human suffering may eventually result [from] these advances in cancer genetics, a number of important questions must be addressed before wide-spread testing of this sort can be recommended.

Two relatively common heritable cancer risk genes have recently been located. Among people with colon cancer, it appears that as many as 10% carry an altered germline copy of a gene called MSH2.(1-3) Individuals with an altered MSH2 gene face an approximately 80% risk of colon cancer; women also have an elevated risk of endometrial and ovarian cancer. Intense medical surveillance may be beneficial in preventing cancer deaths in this high-risk group.(4)

Similarly, approximately 5% of women with breast cancer have inherited an altered copy of the BRCA1 gene, which has been pinpointed to a small region of chromosome 17.(5) As the gene itself has not yet been identified, BRCA1 mutation carriers currently can only be identified by linkage analysis, which requires DNA samples from several affected relatives. A woman with an inherited BRCA1 mutation faces an approximately 85% lifetime risk of breast cancer and an elevated risk of ovarian cancer. Medical or surgical interventions may be effective in reducing the risk of cancer death for these women, but their effectiveness has not been fully evaluated.(6,7)

Despite the promise of these discoveries for benefiting humankind, it is premature to offer testing of either high-risk families or the general population as part of general medical practice until a series of crucial questions has been addressed. These questions include, but are not limited to, the following:

  • How many different mutations of MSH2 and BRCA1 will be found, what are their actual frequencies, and what is the risk of cancer associated with each?
  • What are the technical and laboratory issues associated with detection of mutations in these genes, what frequency of false-positive and false-negative results will occur, and how can quality control of testing be assured?
  • How effective are interventions to prevent cancer morbidity and mortality in high-risk families and in the general population?
  • How can education about the complexities of DNA testing be provided to large numbers of potentially at-risk individuals, how can informed consent be ensured, and how can effective, culturally sensitive, nondirective genetic counseling be offered about such profoundly wrenching issues?
  • Finally, how will the possibility of genetic discrimination against those found to be at high risk be avoided?

Gathering the information and establishing the protocols that will be needed to safely integrate genetic testing and counseling for cancer risk into clinical practice can best be accomplished through a coordinated set of clinical research studies. An initiative to sponsor such studies is currently being launched by the National Center for Human Genome Research, the National Cancer Institute, the National Institute of Mental Health, and the National Institute for Nursing Research. Such studies should be widely available, prepared to handle the magnitude of requests for testing, and should provide as complete information about the tests and their limitations as possible. Until more information is available to address these critical issues, it is premature to offer DNA testing or screening for cancer predisposition outside a carefully monitored research environment.


  1. R. Fishel, M. K. Lescoe, M. R. S. Rao, et al., "The Human Mutator Gene Homolog MSH2 and its Association with Hereditary Nonpolyposis Colon Cancer,"Cell 75, 1027-38 (1993).
  2. F. S. Leach, N. C. Nicolaides, N. Papadopoulos, et al., "Mutations of a Muts Homolog in Hereditary Non-Polyposis Colorectal Cancer," Cell 75, 1215-25 (1993).
  3. R. Parsons, G. M. Li, M. J. Longley, et al., "Hypermutability and Mismatch Repair Deficiency in Rer+ Tumor Cells," Cell 75, 1227-36 (1993).
  4. H. T. Lynch, T. C. Smyrk, P. Watson, et al., "Genetics Natural History, Tumor Spectrum, and Pathology of Hereditary Nonpolyposis Colorectal Cancer: An Updated Review," Gastroenterology 104, 1535-49 (1993).
  5. D. F. Easton, D. T. Bishop, D. Ford, et al., "Genetic Linkage Analysis in Familial Breast and Ovarian Cancer: Results from 214 Families," Am. J. Hum. Genet. 52, 678-701 (1993).
  6. B. B. Biesecker, M. Boehnke, K. Calzone, et al., "Genetic Counseling for Families with Inherited Susceptibility to Breast and Ovarian Cancer," JAMA 269, 1970-74 (1993).
  7. M. C. King, S. Rowell, S. Love, "Inherited Breast and Ovarian Cancer: What are the Risks? What are the Choices?" JAMA 269, 1975-80 (1993).


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