My name is Dena Goldberg and I’m a genetic counselor at the University of California, San Francisco, who specializes in cancer genetics. I see patients and their relatives with a personal or family history of cancer, tumors, or polyps, and use their history to determine the most appropriate genetic test. I use genetic test results in combination with personal risk factors to provide a risk assessment for the patient and their relatives. I also work with their healthcare providers in creating a medical plan for cancer screening and surveillance.

The last few years have brought radical changes in the genetic testing landscape, with the cost of testing decreasing significantly and the availability of direct-to-consumer products. Originally, a test for something like a BRCA mutation could only be ordered through a doctor or genetic counselor. This same testing, however, is now available for anyone to order from home. Although different tests are marketed as being the same, the technology used and access to guidance from a genetic counselor greatly varies. I am going to provide you with a checklist of things to consider when assessing which testing is better for you and your situation.

First, to give you some background, genetic counselors tend to be cautious when it comes to companies that provide at-home testing for high-risk mutations. Part of this apprehension is because individuals who have a rare disease or a high risk for disease tend to be more vulnerable and can be easily targeted by companies and individuals who claim they have a cure or knowledge no one else has. Additionally, because the area of genetic testing is booming, many people are trying to get into the genetic testing space without adequate training or knowledge. For this reason, clinical genetics professionals are naturally suspicious whenever a new company or new test is released, especially when it is marketed directly to the public.

Another challenge to obtaining genetic testing is the misconception that any healthcare provider understands genetics. Genetics is its own expertise, and when a provider doesn’t understand genetics, he or she will not know when to offer testing and will not feel comfortable ordering it. The average healthcare provider has received little to no genetic training and keeping up-to-date with such a rapidly evolving field proves to be impossible with everything else a physician already does. This is why genetic counseling is a separate profession; we are the genetics resource for all other healthcare providers. It is very easy for genetic testing company to send a representative to a healthcare provider’s office and convince them their test is the best test to order. Even if the test is good, however, incorrect interpretation of the test may be detrimental to a patient’s health. Unfortunately, there are many case reports where healthcare professionals who lack adequate training have misinterpreted genetic testing, causing a patient to have unnecessary surgeries, or missing a diagnosis that could have prevented multiple cancers in a family. This is why genetics professionals feel very strongly about being part of the genetic testing process for high-risk mutations in genes like BRCA1 or BRCA2.

On the other hand, requiring a professional with such a specific skill set can create a barrier in the testing process. As genetic testing becomes more commonplace, there won’t be enough professionals to see each person before and after a test. This is where focusing on the end goal becomes so important. If the goal is to get more people tested, thereby catching more actionable mutations, then making genetic testing as accessible as possible is a good thing. No matter how many mutations are identified, however, no good comes of it without the proper guidance and education regarding next steps.

The formula for a well-rounded genetic testing experience is:

Keep this in mind.

In terms of BRCA1 and BRCA2, it is much cheaper and easier to obtain testing today than it was even just a few years ago. Today, anyone can pay to have the test without visiting a doctor or genetic counselor. Some people have even had partial testing without realizing it, due to one of the popular at-home saliva tests. The following is a list of what to consider if you choose to get genetic testing.

1. Testing Technology
When assessing a genetic test, it is important to understand the testing technology. In order to understand this, you will need to know the following:

• BRCA1 and BRCA2 are genes every person has in every cell in his or her body. Each person has two copies of BRCA1 and two copies of BRCA2 in each cell.
• Genes are recipes the cell reads through to make a protein.
• These recipes (genes) are written using an alphabet of just four letters: A, C, G, and T. These are called nucleotides. Nucleotides are read in groups of three to create amino acids.
• BRCA1 is made up of 81,188 nucleotides and BRCA2 is made up of 84,192 nucleotides.

When the word “mutation” or “pathogenic variant” is used, it means there is some sort of significant difference in the spelling of a gene, which, in turn, means the cell cannot read the recipe/interpret the gene. There are many different types of mutations. Some of the most common changes include a single nucleotide that changes to another, or an insertion or deletion of any number of nucleotides. This can happen anywhere along a gene, but some parts of a gene are more important than others, therefore changes in certain locations on a gene may be more detrimental than changes in other parts of the same gene. For the BRCA1 and BRCA2 genes, there are thousands of different types of significant genetic changes (mutations) that alter the final function of the gene. Some of these changes are more common than others, especially within certain populations.

There are several ways to find these diverse types of changes, and since various technologies work in different ways, we must know what we are looking for before we decide on the technology to use. For testing mutations in the BRCA genes, most laboratories use a method called next-generation sequencing (NGS) with deletion/duplication analysis. Some companies use a technique called SNP genotyping.

SNP genotyping (pronounced “snip”) stands for Single Nucleotide Polymorphism. If we break that down— ‘single’ meaning one, ‘nucleotide’ meaning the letters I mentioned earlier, and ‘polymorphism’ meaning a change— then you can understand that a SNP is a single letter change in a gene. Remember, genes have tens of thousands of letters. In SNP testing, the laboratory only looks at SNPs as markers for some of the more common mutations. Specifically, BRCA SNP testing tends to include just three points across both BRCA1 and BRCA2. These three points represent the location of the most common mutations found in the Ashkenazi Jewish population (we know that approximately one in 40 Ashkenazi Jews has one of these three mutations). There are, however, thousands of other points across the BRCA genes where a mutation may be found. The only way to find mutations in these other parts of the gene would be to use a DNA sequencing technology.

DNA sequencing is the process of determining the precise order of nucleotides within a gene. Sequencing reads through every single nucleotide. Next-generation sequencing is a method that has made DNA sequencing much faster and cheaper. Deletion and duplication analysis can be done in conjunction with NGS and looks for small pieces of DNA that are missing or added.

To better understand, imagine this hypothetical situation: you are working at a bookstore that sells used books. In this scenario, you cannot sell any books that have been highlighted or written in and you have a shipment of hundreds of the same textbook to sort through. The textbook is full of short stories and has thousands of pages. You don’t want to flip through every page looking for markings because it would be very time consuming, but you know there are three stories the professor most commonly assigns. You decide to only turn to those three stories in each textbook to assess if there are markings on those pages and you sort the books based on that assessment. In this case, you would identify a number of books with markings, but you would also miss many markings on the thousands of other pages of the books. This technique is equivalent to SNP genotyping.

Now, say your boss purchases a machine that flips through each of the pages to look for markings. This technique will identify many more books that cannot be sold. This machine is like next-generation sequencing; what used to be too cumbersome and slow is now made faster and cheaper with this new technology.

Another thing to keep in mind is that even companies which use sequencing technology may not be able to detect larger rearrangements of genetic material within one of the BRCA genes. Take, for example, a well-known BRCA mutation found in individuals of Portuguese ancestry that involves an insertion of genetic material into the BRCA2 gene. Some laboratories can detect this, but others cannot. This is very important, especially if you have Portuguese ancestry.

Both of these technologies are BRCA genetic tests, but as you now can understand, they are very different. Make sure you understand what type of testing you are receiving. Many companies have this information in the FAQ section of their website, but you should always be able to call customer service to ask if the testing uses next-generation sequencing with duplication/deletion testing for BRCA, or just specific variants or SNPs. If it does use sequencing, ask if they also look for large rearrangements and whether they can detect the Portuguese founder mutation. This will give you an idea about how comprehensive the test is.

2. Genetic Counselor Involvement

Another indicator of a well-developed test is if there was any genetic counselor involvement in the continued development of the test report, and if a genetic counselor is available through the company with whom you can speak. This plays into my equation for a good genetic testing experience because offering genetic counseling from a board-certified genetic counselor provides the education about what the findings mean.

Additionally, since many genetic test reports are sent to patients, the wording must be consistent and up-to-date with current recommendations and be written in patient-friendly language. Genetic testing reports are always changing and adapting to recommendations. The language used in the report and the ability to stay on top of guidelines is best handled by a clinical genetics professional at the laboratory such as a geneticist or genetic counselor.

3. How Results are Delivered

Some companies may be doing research and offer a free “BRCA test” or offer testing online at a reduced cost. When it comes time to disclose the results, however, they send a letter, provide the results online or have an individual with no formal genetic training deliver results. This can create a lot of anxiety in the patient because there is no expert to speak with who can explain the implications of the results. In this situation, the patient is left to find answers on his or her own, and Google is never a good replacement for a BRCA expert. Again, any legitimate company will provide a genetics professional to deliver results or answer questions after results are released.

4. Privacy

Some genetic testing companies will automatically share your anonymous data with other companies or researchers. Other companies will give you the option to choose whether you want to share your data or not. This is something to read or ask before providing a sample.

5. Cost

What many people fail to realize is genetic testing is frequently covered by insurance. A genetic counseling visit is also likely to be covered and sometimes even offered at a discounted rate, if it is not. Sometimes making the appointment to see a genetic counselor can save money because part of our job is finding the most appropriate AND affordable option for genetic testing.

Additionally, for a person with a relative with a BRCA or other hereditary cancer syndrome gene mutation, testing is always covered by insurance or heavily discounted. Instead of paying for a big, expensive genetic test, it is important to check what the options are. I have seen patients who waited a long time to test because their doctor told them it would cost thousands of dollars out-of-pocket. They were shocked to hear the same exact test could be covered by their insurance.

These are some of the most important factors to think about when determining the best test for you. Ordering testing from home is much easier and faster for some people, but seeing a genetic counselor is still a better option for others. What works well for one person may not work for another. Whichever you choose, please make sure you understand what you are buying and take some time to think about how this information will affect you.

To learn more about different genetic testing companies, I will be posting reviews of different genetic tests shortly on my website at http://www.denadna.com.