Should patients be told about incidental findings from genetic testing?

Genomics is moving at a lightning pace. Whole genome sequencing, a special type of genetic test, can produce much more information about a person’s genes than ever before. However, this rapid advance in technology has outpaced our ability to understand what to do with all of this additional information. As a result, patients and clinicians are faced with difficult decisions.

Whole genome sequencing grows as a clinical tool

Genetic testing has traditionally been used for genetic abnormalities that are highly predictive of specific diseases and conditions. For example, women who have the BRCA1 gene mutation have a much higher than average risk of developing breast and ovarian cancer. Women with breast cancer who have the HER2/neu gene mutation are more likely to respond to treatment with the drug Herceptin than those who do not.

In both of these cases, the genetic tests are carried out on a narrow set of genes specified by clinicians. Whole genome sequencing is different.

Whole genome sequencing maps the entire sequence of a person’s genome. The cost of sequencing a whole human genome has decreased from $95 million in 2001 to $4,000 in 2014. One company recently claimed it will shortly sequence the genome for $1,000. As the price of whole genome sequencing continues to drop, its use as a clinical tool has grown, and will likely continue to grow.

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While whole genome sequencing is a major scientific advance, it’s still very new technology. A 2014 article found that interpreting the full genome remains difficult, is time consuming and can be subjective. A small Stanford-based pilot study found that multiple doctors interpreting the data often disagreed about the potential of certain findings to cause disease. Reaching consensus on the analysis meant that multiple doctors and genetic counselors were required to interpret the data. In addition to raising concerns about the reliability of interpretation by a single doctor, this study found the cost of interpreting the test was $17,000.

Incidental findings cause ethical concerns

But perhaps the greatest challenge that arises from sequencing whole genomes is that in some cases additional information may be revealed that doctors had not been looking for specifically. These are called incidental findings.

For example, patients whose cancer is sequenced to determine which therapy might be most effective, could also be found to have a genetic profile that indicates they have an elevated risk of developing Alzheimer’s disease later in life. This is an incidental finding.

Incidental findings pose challenges for doctors and patients, because the relevance of the incidental finding to the patient’s health may not be clear or be unknown.

For most diseases, genes only partly influence the risk of developing a disease, with factors such as lifestyle and environment also playing an important role. Having a particular gene may only increase the risk of an illness by a few percentage points, and the presence of that gene may tell us little about the severity of the disease or its timing. Unfortunately, as one article in the British Medical Journal states, this uncertainty is often“underappreciated by both clinicians and the public, many of whom regard genetic information as highly deterministic.” The perception that genes are destiny means incidental findings may be over-interpreted by both doctors and patients, potentially leading to treatments that are unnecessary or even harmful.

And even when the significance of a finding is relatively certain, some patients may not want to know that they are at elevated risk of a genetic disease, because they feel it would cast a shadow over their lives. This is especially true of genetic conditions for which there is no effective treatment, such as Alzheimer’s disease.

One way of addressing the challenges of incidental findings is to limit the number of genetic variations that are reported to patients. Nearly all organizations that have developed policies addressing the reporting of incidental findings to patients have limited reporting to findings that are scientifically valid, have serious health implications, can be prevented or detected earlier through screening, or can be treated with evidence-based therapies.

However, some experts argue that these policies are paternalistic. They favour full disclosure of test results from whole genome sequencing, even when these results are not well understood. They suggest that test results can position patients to be better stewards of their own health and wellbeing. There may also be a legal obligation to disclose incidental findings.

Other experts believe patients should be informed about incidental findings in a manner that allows them to choose what information is returned to them and when. They suggest a self-guided approach that enables individuals to self-select among results provided to them, in a manner that aligns with their individual value systems.

In March of last year, the American College of Medical Genetics and Genomics released guidelines recommending physicians report incidental findings from 56 genetic variations. These include genes associated with a number of hereditary cancers, as well as a range of other genetic conditions, such as Marfan Syndrome. These 56 genes were identified because they increase the risk of diseases that cause considerable morbidity or mortality, and there are established evidence-based treatments that can improve outcomes.

However, after a year of vigorous debate, the college amended the guidelines in this April to specify that patients should be provided with the option of opting out of having their incidental findings released to them before conducting the test that would generate these results.

Helping patients interpret incidental findings

It is increasingly recognized that patients’ understanding of the results and consequences of genetic tests are an integral part of genetic testing. A broad range of tools are coming into use to help patients and physicians gain a basic understanding of the benefits and limitations of current genetic testing and the information it reveals. However, the scale of counselling and support required to meaningfully convey the complexity of many incidental findings is considerable, and the capacity to provide this information is limited, with few standards.

One example offered by Pascal Borry, assistant professor at the Centre for Biomedical Ethics and Law from K.U. Leuven University in Belgium, is the European Commission’s project Eurogentest, which provides plain language pamphlets about genetic tests.

“Clinicians have concerns about the downstream costs of these findings, as well as the interests of the patient sitting in front of them,” says June Carroll, an associate professor at the University of Toronto’s Department of Family and Community Medicine. Carroll is part of a partnership between Mount Sinai Hospital, the University of Ottawa, the Children’s Hospital of Eastern Ontario and the University of Toronto, which has created GEC-KO, a project that provides point-of-care tools for clinicians to better understand genomic testing.

While these tools are useful for a general overview of genetic testing, more specific tools offering guidance for incidental findings have also been developed. Philippe Beddard, a clinician at Princess Margaret Hospital, and his colleagues use a digital tool to prepare patients for their discussions with genetic counselors prior to revealing the test results to them.

Yvonne Bombard, a genomics and policy researcher at St. Michael’s Hospital in Toronto, says “clinicians ordering the test must be in a position to help patients make decisions about which findings they wish to learn about.” Bombard is collaborating with Beddard on the development of a decision aid to guide patients’ decisions about which incidental findings they wish to receive.

The tool will be used by clinicians to help patients considering undergoing whole genome sequencing and the general public when considering enrollment in research that could produce incidental findings. The tool will explain in plain language the risks and benefits of learning about specific categories of incidental findings.

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1 Comment
  • Christopher McCabe says:

    The question formulation appears to assume that all information is knowledge and that the key difference is actionable and non-actionable knowledge. %featured%Much of the genetic information is only descriptive – it is not only non-actionable, it is non-interpretable. %featured% To present respondents with a full set of meaningful responses I think the response options would need to include the following: a) know nothing; (b) know only actionable information; (c) know actionable or interpretable information; and (d) know all information even if it is neither actionable nor interpretable.

    The current form of the questions leaves open the possibility that respondents are assuming that all information is interpretable, and it is possible that people preferences and attitudes differ between interpretable and uninterpretable information. If the current 48% who would want to know everything had different preferences over interpretable and non-interpretable information, this could change the policy implications of your results.

    Interesting read by the way.


Sophia Ikura


Sophia Ikura is the founder and executive director of the Health Commons Solutions Lab, a not-for-profit health and social enterprise located at Sinai Health in Toronto.

Timothy Caulfield


Timothy Caulfield is an author and Canada Research Chair in Health Law and Policy, University of Alberta.

Terrence Sullivan


Terrence Sullivan is an editor of Healthy Debate, the former CEO of Cancer Care Ontario and the current Chair of the Board of Public Health Ontario.

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