A Negative Genetic Test Result Reduces The Unnecessary Burden Of Anxiety

Board certified Genetic Counselor Dr. Mansi Vishal talks about the scenarios where genetic counselling is beneficial and where its not necessary. A useful interview that helps us understand the role of genetics in cancer.

What is genetic counselling or genetic consultation?

As per the standard definition by National Society of genetic Counselors (NSGC), Genetic counselling as a process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. 

Can you share some of the concerns and myths around genetic testing? 

Overall, there is less awareness amongst people about Genetic testing options because in many healthcare settings, there are no Genetics professionals. One of the common myths is about usefulness of Genetic testing. People think that if something causal is present in genes and I am going to get the disease few years down the line, why should I increase my anxiety by doing a test and know about it now. 

One of the reasons behind this thinking is that they are not aware that they can go for early screening and prevention of the diseases before getting it. If they get to know that they are at risk of a certain genetic condition, they can plan their lives; can take important decisions about family planning. On the other hand, negative genetic test result reduces the unnecessary burden of anxiety about carrying the faulty gene in their DNA. Another myth is about passing on the faulty gene in the next generation. People think that if I carry the gene mutation, I will surely pass it on to the next generation. However, the truth is that there is 50% chance to pass on the faulty gene and equal chances of passing on the normal copy of the gene. These myths need to be addressed by the Genetic counselor before testing. This is known as pre-test genetic counseling. 

The costs of genetic testing are quite high.  What are the real benefits of genetic testing?  For people with strong family history of cancer and for those with no known cases of cancer

Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests. A positive result can direct a person towards available prevention, monitoring, and treatment options. Some test results can also help people make decisions about family planning. Costs are relatively on higher side but it is far less than the cost of treatments if someone gets cancer. 

Positive family history of cancer helps raising the red flag to seek genetic consultation. It increases the risk of getting cancer because most of the times, hereditary cancers follows autosomal dominant pattern of inheritance which means that there is 50% chance of inheriting the DNA change causal to cancer from the affected parent. Also, there is 50% chance for the siblings of the affected individual to carry the same DNA change. Therefore, doing the genetic test in the affected relative first, tells about the genetic mutation in that particular family. Once the familial mutation is identified, testing the other family members for the known familial mutation guides the relatives for surveillance and management options. Here, selection of appropriate genetic test is very important and also, who should get tested first in the family. 

Many a times, a single case with cancer comes but there is no family history. In that case, histological features of that particular cancer become important to decide for genetic testing. For e.g., a single case of triple negative (ER/PR/HER2 -ve) breast cancer at 27 years of age warrants genetic testing because statistics says that there are high chances of inherited mutations in these women in BRCA1/2. BRCA1 and BRCA2 are responsible for hereditary breast and ovarian cancer (HBOC) syndrome which can cause breast cancer, ovarian cancer, male breast cancer, prostate, pancreatic cancers and melanomas.

How does a cancer genetic test get done?

Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or Genetic Counselor can order the test. Genetic testing is often done as part of a genetic consultation. Genetic tests are performed on a sample of blood or saliva. The sample is sent to a laboratory where scientists/researchers look for specific changes in DNA. The laboratory reports the test results in writing to a person's doctor or genetic counselor, or directly to the patient if requested. It takes about 3-4 weeks to get the report.

At what stage in the cancer journey should the patient go for genetic testing? Does age play a factor?

Earlier is better always. Visit to a Genetic counselor or a Geneticist is recommended before doing a genetic test. These are trained professionals who will take the proper family and personal medical history and use that as a guide to suggest for an appropriate genetic test. In cancer, there is a direct role of genetic testing in early detection, management and surveillance. Therefore, unaffected individuals should seek Genetic consultation as soon as they become aware about anyone in their family with history of cancer. If any person is affected with cancer before 50 years of age, they should seek Genetic consultation as early as possible after disease diagnosis.

Since most hereditary cancer syndromes are adult-onset conditions, testing a minor is not recommended in most of the cases. There are ethical concerns behind genetic testing before 18 years of age. Genetic counselors are aware about these aspects. So, one can discuss the testing options with them.

For which cancers are genetic counseling and testing recommended?

Cancer is a Genetic disease which means that it is caused due to changes in DNA. But it’s not always hereditary. 5-10% of the all cancers are hereditary. Following are the few common cancer types for which Genetic counseling and testing is recommended especially in early onset cases (age of onset<50y): Breast cancer (male and female), ovarian cancer, colorectal cancer, gastric cancers, uterine/endometrial cancer, pancreatic cancer, thyroid cancer, skin cancer and brain cancers. If there is a combination of these in one individual or in multiple individuals of the same family, genetic consultation is strongly recommended. 

What are the current available genetic tests for cancer risk prediction and treatment?

Genetic tests are used for genetic diagnosis of a hereditary cancer syndrome and for risk prediction of unaffected individuals. These are known as germline tests. Targeted gene sequencing for somatic mutation testing not only provides the efficacy of a number of therapeutics targeting the protein products of specific genes but also elucidates the predictive and/or prognostic markers that are altered in human cancer. Genetic testing in cancer is available as single gene tests for a specific suspicion of hereditary cancer syndrome or a comprehensive panel test can be ordered which covers multiple genes in a single test. In recent years, the testing approach has moved from single gene test to panel based testing because of advances in research and technology. It has several advantages especially decreased cost , decreased need for sequential testing and more precise information. Therefore, panel testing is recommended over single gene testing. This remains true for somatic testing too.

PE Tip: According to ASCO, it is imperative that patients undergoing panel genetic testing have proper counseling, as the results of panel testing may not always be straight-forward. Panel testing can be associated with significant challenges and risks as well as benefits; these should be explained to patients prior to initiation of testing. Patient preferences should be included in decision making regarding the most appropriate test.

Are there any cancers where genetic testing is not recommended at this point? For instance if there is no treatment associated with a specific mutation

For mouth, lung and liver cancers, inherited mutations are not common because these are mostly associated with exposure to agents like tobacco, smoking and drinking habits etc. For lung cancer, somatic testing options are available in which testing is done on the cancer tissue or from blood which is known as liquid biopsy test. These tests help in deciding the treatment strategies for lung cancer patients. Few common mutations are EGFR, ALK, ROS-1, K-RAS, c-MET. Also, cervical cancer is mostly caused due to infection of Human Papillomavirus (HPV) but if someone is not positive for HPV and there is family history of other cancers, one should consult a Geneticist or genetic counselor to check the probability of a hereditary cancer syndrome. Overall, if there are clusters of individuals with one subtype or different cancer subtypes in a family, they should come for genetic consultation in order to know the individualized risk and to know whether genetic testing is appropriate for them.    

Are there any scenarios under which genetic testing would not be advised?

Yes, testing is not recommended if the onset of cancer occurs at a much later age and with no significant family history. However, family history taking is a pre-requisite to decide whether genetic testing is important or not.

What are the concerns that need to be addressed based on the results of genetic testing? Family counselling? Family testing? Is mutation testing required for all types of cancers?

If a genetic test result turns out to be positive for a pathogenic mutation, then screening, surveillance, management and treatment options will be suggested to the patient in a post-test counseling session by a trained Genetics professional. National Comprehensive Cancer Network (NCCN) has given recommendations for the above. The results are also discussed with the healthcare providers in order to take important decisions about the treatment. Genetic testing for the family members especially the first degree relatives (siblings, parents and children) is also recommended. For hereditary cancers, one single gene is responsible for different types of cancers. Therefore, screening recommendations and surgery options are given accordingly. If the genetic test result is negative, then the individual carries a general population risk of getting cancer and there is no additional risk of passing it to next generations. Sometimes, we get variants of unknown significance (VUS) in a genetic test report for which counseling is separately needed in a post-test counseling session. In addition, there are many psychosocial aspects which are involved around genetic testing. These concerns need to be addressed by a Genetic counselor. 

What should be the basis of choosing a right lab for the genetic test?

Genetic tests are the advanced tests utilizing current and latest next generation sequencing technology because of which quality control of the generated data is very crucial. Good Genetic diagnostic labs have expertise for quality data generation and analysis which can pick up the actual DNA variants avoiding false positive and false negative results. The genetic test reports can be judged on the basis of proper references for the methodologies used, data quality measures and the clinical utility of results provided in the reports. The tests should be sent to laboratories which are accredited by College of American Pathologies (CAP) and National Accreditation Board for Testing and Calibration Laboratories (NABL). The accrediting processes by both organizations are designed to ensure that laboratories comply with the highest standards, and adhere to rigorous criteria for quality assurance.

Dr. Mansi Vishal is a board certified Genetic Counsellor, working for Strand Life Sciences. She has done Ph.D in Genetics from CSIR-IICB, Kolkata and has worked in the field of Genetics for 10 years