South Florida Hospital News
Wednesday August 5, 2020

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June 2016 - Volume 12 - Issue 12


Germline Genetic Testing Raises Thorny Ethical Questions

The simply stunning advances in our understanding of the molecular basis of human disease are providing revolutionary changes in the management of multiple illnesses. It is well recognized that cancer has been at the leading edge of this paradigm change through the demonstration of the clinical utility associated with knowledge of the unique genomic profile present within an individual patient’s malignancy. Not surprisingly, the past and current major focus of using molecular testing has been in the treatment of an established malignancy, and in examining for the presence of particular mutations, rearrangements, or amplifications of specific genes that may suggest the delivery of a particular antineoplastic agent targeted to that abnormality.

Patients with cancer and their oncology teams are witness to increasingly relevant advances in this arena in multiple clinical settings. Another critically important and highly clinically relevant issue - one that is less frequently discussed among oncologists - concerns the implications of knowing the germline genetic background for individuals with known cancer or who are at a higher risk for developing a malignancy. Cancers of the colon, breast, and ovary are excellent examples where germline testing has been shown to be of value and where prophylactic interventions in specific clinical settings have been documented to be of substantial utility.
However, there is a particular issue when a search is undertaken to discover unique normal polymorphisms or actual mutations that may be present in the germline - versus a sole focus on molecular abnormalities within the cancer itself - that requires particularly careful consideration and discussion. When cancer is present, what is specifically being explored are differences between the individual’s germline versus the cancer, with the goal of finding a target for therapy. In essence, the germline itself is purposefully ignored since there is no intent to target the normal genome. But when the normal germline is examined to define cancer risk, evaluate genetically influenced probability of treatment-related toxicity, or for other purposes such as assisting in the determination of prognosis, there is the realistic potential that what might be found would include incidental genetically relevant markers associated with illnesses completely unrelated to the intent of the specific search.
Should individuals undergoing genomic testing be asked if they would like to receive this information if it is discovered? This request could be made prior to obtaining the testing or after the results are available and a laboratory reports the presence of such incidental information. This is a complex and controversial issue, with considerable ongoing debate.
Included in the discussion are questions of whether the individual or her/his family would be able to take any action following notification of the results that may lead to a decreased risk of a suggested negative outcome, or conversely whether the information would solely be anxiety-provoking with no current potential to be actionable. Hopefully, as the cancer research community develops effective screening strategies to discover early-stage cancers such as CT scanning for lung cancer and prophylactic approaches to prevent the development of malignant disease as is the case with bilateral salpingo-oophorectomy for ovarian cancer in the presence of a BRCA mutation, the conclusion that nothing actionable is possible will become an increasingly rare statement.

Dr. Maurie Markman is the editor-in-chief of OncologyLive magazine (, where this article originally appeared.  He also is president of Medicine & Science at Cancer Treatment Centers of America, and clinical professor of Medicine, Drexel University College of Medicine. He can be reached at See more information at

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