Genetic Screening for Cancer Prevention: Many Choices

Issue 28, Winter/Spring 2016


Sequencing the human genome for the first time cost about the same as building an aircraft carrier. But now, large genetic tests are available for about the same price as bicycles. Whole genome and exome (the part of the genome that is most important for human disease) sequencing has now become mainstream for diagnosing rare disorders and cancer therapy targets.

As costs have declined, the trend is moving towards using it in broader groups of people for more precise estimation of disease risk, including for cancer prevention.

For children who develop cancer, genetic testing can identify mutations to explain the cause in about one in 10, and an additional one in six had a mutation in their tumor that could guide therapy in the event of cancer recurrence. For adults with more than one close relative with breast, colorectal or certain rare tumors, about one in 10 to one in 15 will have a mutation identified by genetic testing that alters cancer screening. For men with prostate cancer that has spread beyond the local stage, almost one in five will carry a mutation in a gene linked to DNA repair and cancer risk, and their families can potentially benefit from more intensive screening.

Even for people without a strong personal or family history of any disease, screening 76 genes that by expert medical consensus influence clinical management (including cancer screening) will identify about one in 20 who carry a mutation in an “actionable” disease – that is, one that will influence their medical care.

Thus, currently about 6% of the American population belong to families with a known genetic disease mutation, a little less than one percent of which relates to cancer risk.

There are now a wide range of genetic tests available to healthy individuals concerned about their longevity that can be ordered by a physician to assess cancer risk, ranging from the very expensive to the very affordable. Direct-to-consumer genetic tests (ordered without a physician or genetic health professional) for cancer risk individualization have come under increased scrutiny by the US Food and Drug Administration, which regulates medical testing.

On the high end in terms of cost, Human Longevity Sciences offers the HealthHub. Geared towards concierge medicine, patients visit their offices in La Jolla, California, London, Singapore or other locations. Patients have their whole genomes sequenced in addition to an analysis of their gastrointestinal microbiome; screening with new preventative medicine technologies such as brain-fast MRI; atherosclerosis scanning and wearable technology monitoring of blood pressure, heart rate and other real-time datastreams.

The cost is many thousands of dollars for an initial visit, with annual follow-up visits at an additional cost. Patients receive recommendations for individualized cancer screening for breast cancer (e.g., MRI, mammography), colorectal, lung, prostate and other cancers that they follow up with their regular physicians.

Whole exome sequencing, which screens all 20,000 human genes, is also available – with a price tag of many thousands of dollars. This screens for “spelling mistakes” that cause mutations for both common and rare genetic causes of cancer, along with all other diseases. However, depending on the testing laboratory, some miss mutations that rearrange large parts of genes (called structural variants), and so people interested in whole exome sequencing should be sure to go to a physician or genetic health professional who is well-versed in the technical details of laboratory testing.

There are about 150 genes whose mutation has been associated with increased cancer risk, although some of these are extremely rare. There are a variety of more focused gene panel tests, ranging from one gene to dozens that are usually oriented around increased risk of specific malignancies, such as breast and ovarian cancer. Most (but not all) laboratories performing gene panel tests detect both spelling mistakes and structural variants, and so can actually be superior to whole exome sequencing.

For individuals who have strong personal or family histories of specific constellations of malignancies – for example, colorectal and endometrial cancer – many insurers will cover testing ordered by a physician or genetic health professional.

However, for individuals whose medical insurance will not cover genetic testing, the price of high quality gene panels has recently become much more affordable. Invitae, a San Francisco based genetic testing company, has high-quality gene panel tests that cost a few hundred dollars when billed directly to patients and which covers up to 79 cancer risk genes. Invitae is also coming out with another panel-based test for the same price that covers 76 genes (including both cancer and non-cancer genes) that genetic professional experts agree should directly influence medical care. Color is another company offering a 24-gene panel for breast/ ovarian cancer, again priced at a few hundred dollars.

Another option is to participate at no cost in the Precision Medicine Initiative Cohort Program. The Precision Medicine Initiative Cohort will build a large research cohort of 1,000,000 or more Americans. Stated official goals include developing quantitative estimates of risk for a range of diseases by integrating environmental exposures, genetic mutations, and gene-environment interactions; identification of determinants of individual variation in the efficacy and safety of commonly used therapeutics, and the discovery of biomarkers that identify people with increased or decreased risk of developing common diseases.

The Precision Medicine Initiative Cohort will commence recruiting patients in November 2016 from all geographic regions of the United States. However, it is likely that not all PMI-enrolled individuals will have their genomes sequenced, as there are currently no funds dedicated for this purpose, and there is no timeline for when participants will have genome sequencing performed, and genetic information returned to them, if at all.

A question frequently raised by patients is whether having genetic tests will change the premiums that they pay for insurance. In May 2008, President George W. Bush signed into law the Genetic Information Non-Discrimination Act, or GINA. This legislation prohibits genetic discrimination in both employment and health coverage.

Specifically, insurers and employers who have more than 15 employees are not allowed to request genetic information to be used in any of their decisions. However, small businesses are exempt because of concerns over the cost of administration.  Also importantly, GINA does not protect against discrimination involving life, disability, and long-term care insurance.

This is not theoretical, but a real-life situation, and I have patients who have been denied life insurance because of a genetic diagnosis. As an example, I will discuss one patient in my practice who has Lynch syndrome. This is a genetic cancer susceptibility disease that increases the risk for colorectal, uterine, ovarian and other cancers and is caused by mutations in MSH2, MLH1 and other genes. My patient is in her 50s and had surgery to remove her colon, uterus and ovaries. She has never developed any cancer and is diligent in keeping up with cancer screening in order to work and take care of her family. Despite her meticulous care to stay healthy, my patient was denied life insurance, largely because of her genetic diagnosis. The denial letter from her insurer read:

“Like all insurance companies, we have guidelines that determine when coverage can or cannot be provided. Unfortunately, after carefully reviewing your application, we regret that we are unable to provide you with coverage because of your positive finding of a mutation in the MSH2 gene, which causes the Lynch syndrome, as noted in your medical records.

If you received any correspondence prior to this letter that you interpret as coverage, please disregard it. You do not have coverage. Also, if you have an existing policy that you were replacing, please continue paying the premiums on that policy.”

Consequently, many people who are interested in having genetic testing may want to obtain life, disability and/or long-term care insurance prior to tests.

In summary, there are currently many different options for genetic testing for cancer prevention. Genetic testing has many complicated technical, legal and social details that can influence whether testing is appropriate for each person. The best course of action is for a person who is considering having testing to meet in person with a physician or genetic counselor regarding whether genetic testing is right for them.

Dr. Steven Monroe Lipkin

Steven Monroe Lipkin. MD, PhD
Director, Program in Mendelian Genetics
Department of Medicine
Weill-Cornell Medicine
New York, NY