The incidentalome and the genome

For those of you who have been concerned about the implications of the human genome and the emergence of the human metabolome, there is another strange new creature born of modern science and  roaming our planet, the incidentalome. The incidentalome is a bizarre creature without clearly defined shape or form but it is not certainly not mythical. Kohane, and others have described the incidentalome as the universe of all possible incidental findings. While this universe of possibilities is not new, its boundaries are rapidly expanding as diagnostic procedures have evolved substantially.

One traditional example is the finding of tumors and other growths of unknown significance. Studies have shown that many surgeries, such as a significant minority of mastectomies, are performed due to the identification of growths that in the absence of diagnosis and surgery would not develop into significant health problems. Unfortunately, while advanced imaging techniques have increased the finding of abnormal growths, it has not helped us to distinguish between some malignancies that will never develop into dangerous growths and others that will. As a result, we know on an epidemiological level that some surgeries are being performed unnecessarily but on an individual level, we don’t know if this is the case or not.

The mapping of the human genome, gene-chip technology, and chromosomal microarray analysis have had major effects in expanding the incidentalome. Tests that may be intended to confirm or rule out one or a few conditions have the potential to identify thousands of others. Two associated problems contribute to this concern. First , the mapping of the genome allows us to identify atypicalities of unknown or poorly understood significance. In a sense this creates the circumstance in which your Doctor can diagnose you as having a disease that hasn’t been discovered yet. If someone actually does discover it later, we will let you know about it.

Second, since all tests have the potential for false positive results, the chances of a false positive are vastly increased with tests like chromosomal microarray analysis. For example, if each individual test has a 1% chance of a false positive, a test that tests for 1700 different conditions is likely to produce numerous false positives.

This kind of testing also raises issues about consent. Normally, it would be necessary for the physician to explain what is being tested for with single test. Does this mean that when a procedure tests for thousands of conditions, the physician needs to explain each one to obtain consent? What if the test reveals a condition that the patient did not wish to be tested for?

So, while the incidentalome itself remains poorly described or understood, it is a real phenomenon that presents major problems for health care, and raises major questions about how much we really want to know about our biological selves.

Kohane IS, Masys DR, Altman RB (Jul 2006). “The incidentalome: a threat to genomic medicine”. JAMA 296 (2): 212–5.

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